UNIVERSITY  OF  CALIFORNIA 

MEDICAL  CENTER  LIBRARY 

SAN  FRANCISCO 


OF 

L* — 

A    TEXT-BOOK 


OF 


PHYSIOLOGY 


FOR 


MEDICAL  STUDENTS  AND  PHYSICIANS 


BY 

WILLIAM   H.    HOWELL,   PH.D.,  M.  D.,  Sc.  D.,  LL.D. 

PROFESSOR    OF   PHYSIOLOGY    IN   THE  JOHNS   HOPKINS   UNIVERSITY,    BALTIMORE 


Scventb  ;6&ition,  aborougbls  TReviseD 


PHILADELPHIA   AND    LONDON 

W.  B.  SAUNDERS  COMPANY 

1919 


Copyright,  1905,  by  W.  B.  Saunders  and  Company.    Reprinted  February,  1906,  September, 
1906,  and  January,  1907.    Revised,  reprinted,  and  recopyrighted  August,  1907.    Re- 
printed January,  1908,  and  October,  1908.    Revised,  reprinted,  and  recopyrighted 
August,  1909.    Reprinted  January,  1910,  and  July,  1910.    Revised,  re 
printed,  and  recopyrighted  August,  1911.    Reprinted  January,  191 2e 
and  October,  1912.     Revised,  reprinted,  and  recopyrighted 
September,  1913.    Reprinted  August,  1914.    Revised, 
reprinted,  and  recopyrighted  September,  1915. 
Reprinted   March,    1916,  January,  1917, 
May,  1917,  and  March,  1918.    Re- 
vised, reprinted,  and  recopy- 
righted September,  1918 


Copyright,  1918,  by  W.  B.  Saunders  Company 


Registered  at  Stationers'  Hall,  London,  England 


Reprinted  March,  1919 
Reprinted  September,  1919 


PRINTED    IN    AMERICA 

PRESS    OF 

W.     B.     SAUNDERS     COMPANY 
PHILADELPHIA 


PREFACE  TO   THE  SEVENTH   EDITION. 


IN  this,  as  in  former  editions,  no  fundamental  change  has  been 
made  in  the  contents,  arrangement  of  material,  or  the  general 
principles  of  presentation  which  were  originally  adopted.  But  in 
the  three  years  that  have  elapsed  since  the  sixth  edition  the 
natural  expansion  of  physiological .  and  medical  research  has 
yielded  much  new  information.  To  incorporate  the  main  feat- 
ures of  this  added  knowledge  it  has  been  necessary  to  make 
many  alterations.  Throughout  the  work  additions,  substitutions, 
and  omissions  have  been  used  freely  in  order  to  bring  the  book 
up  to  date  as  nearly  as  possible. 

It  is  now  thirteen  years  since  the  first  edition  appeared.  Dur- 
ing this  period  the  author  has  tried  faithfully  in  the  successive 
editions  to  keep  the  book  in  line  with  our  advancing  knowledge. 
It  is  not  probable  that  he  has  been  wholly  successful  in  these 
attempts,  for  the  literature  bearing  upon  the  subject  has  increased 
steadily  in  volume  and  complexity,  but  certainly  he  has  not 
altogether  failed.  The  book  has  moved  with  the  current  of  con- 
temporary physiological  thought,  as  a  text-book  must  if  it  is  to 
be  useful  to  its  clientele  of  students. 

W.  H.  HOWELL. 


PREFACE. 


In  the  preparation  of  this  book  the  author  has  endeavored  to 
keep  in  mind  two  guiding  principles:  first,  the  importance  of 
simplicity  and  lucidity  in  the  presentation  of  facts  and  theories; 
and,  second,  the  need  of  a  judicious  limitation  of  the  material 
selected.  In  regard  to  the  second  point  every  specialist  is  aware 
of  the  bewildering  number  of  researches  that  have  been  and  are 
being  published  in  physiology  and  the  closely  related  sciences,  and 
the  difficulty  of  justly  estimating  the  value  of  conflicting  results. 
He  who  seeks  for  the  truth  in  any  matter  under  discussion  is  often- 
times forced  to  be  satisfied  with  a  suspension  of  judgment,  and 
the  writer  who  attempts  to  formulate  our  present  knowledge 
upon  almost  any  part  of  the  subject  is  in  many  instances  obliged 
to  present  the  literature  as  it  exists  and  let  the  reader  make  his 
own  deductions.  This  latter  method  is  doubtless  the  most  satis- 
factory and  the  most  suitable  for  large  treatises  prepared  for  the 
use  .of  the  specialist  or  advanced  student,  but  for  beginners  it  is 
absolutely  necessary  to  follow  a  different  plan.  The  amount  of 
material  and  the  discussion  of  details  of  controversies  must  be 
brought  within  reasonable  limits.  The  author  must  assume  the 
responsibility  of  sifting  the  evidence  and  emphasizing  those  con- 
clusions that  seem  to  be  most  justified  by  experiment  and  obser- 
vation. As  far  as  material  is  concerned,  it  is  evident  that  the 
selection  of  what  to  give  and  what  to  omit  is  a  matter  of  judg- 
ment and  experience  upon  the  part  of  the  writer,  but  the  present 
author  is  convinced  that  the  necessary  reduction  in  material 
should  be  made  by  a  process  of  elimination  rather  than  by  con- 
densation. The  latter  method  is  suitable  for  the  specialist  with 
his  background  of  knowledge  and  experience,  but  it  is  entirely 
unfitted  for  the  elementary  student.  For  the  purposes  of  the 
latter  brief,  comprehensive  statements  are  oftentimes  misleading, 
or  fail  at  least  to  make  a  clear  impression.  Those  subjects  that 
are  presented  to  him  must  be  given  with  a  certain  degree  of  full- 
ness if  he  is  expected  to  obtain  a  serviceable  conception  of  the 
facts,  and  it  follows  that  a  treatment  of  the  wide  subject  of  physi- 
ology is  possible,  when  undertaken  with  this  intention,  only  by 
the  adoption  of  a  system  of  selection  and  elimination. 

The  fundamental  facts  of  physiology,  its  principles  and  modes 


4  PREFACE. 

of  reasoning  are  not  difficult  to  understand.  The  obstacle  that 
is  most  frequently  encountered  by  the  student  lies  in  the  com- 
plexity of  the  subject, — the  large  number  of  more  or  less  dis- 
connected facts  and  theories  which  must  be  considered  in  a  dis- 
cussion of  the  structure,  physics,  and  chemistry  of  such  an  intri- 
cate organism  as  the  human  body.  But  once  a  selection  has  been 
made  of  those  facts  and  principles  which  it  is  most  desirable  that 
the  student  should  know,  there  is  no  intrinsic  difficulty  to  prevent 
them  from  being  stated  so  clearly  that  they  may  be  comprehended 
by  anyone  who  possesses  an  elementary  knowledge  of  anatomy, 
physics,  and  chemistry.  It-  is  doubtless  the  art  of  presentation 
that  makes  a  text-book  successful  or  unsuccessful.  It  must  be 
admitted,  however,  that  certain  parts  of  physiology,  at  this  par- 
ticular period  in  its  development,  offer  peculiar  difficulties  to  the 
writers  of  text-books.  During  recent  years  chemical  work  in  the 
fields  of  digestion  and  nutrition  has  been  very  full,  and  as  a  result 
theories  hitherto  generally  accepted  have  been  subjected  to  crit- 
icism and  alteration,  particularly  as  the  important  advances 
in  theoretical  chemistry  and  physics  have  greatly  modified  the 
attitude  and  point  of  view  of  the  investigators  in  physiology. 
Some  former  views  have  been  unsettled  and  much  information 
has  been  collected  which  at  present  it  is  difficult  to  formulate  and 
apply  to  the  explanation  of  the  normal  processes  of  the  animal 
body.  It  would  seem  that  -in  some  of  the  fundamental  problems 
of  metabolism  physiological  investigation  has  pushed  its  experi- 
mental results  to  a  point  at  which,  for  further  progress,  a  deeper 
knowledge  of  the  chemistry  of  the  body  is  especially  needed.  Cer- 
tainly the  amount  of  work  of  a  chemical  character  that  bears  di- 
rectly or  indirectly  on  the  problems  of  physiology  has  shown  a  re- 
markable increase  within  the  last  decade.  Amid  the  conflicting 
results  of  this  literature  it  is  difficult  or  impossible  to  follow  always 
the  true  trend  of  development.  The  best  that  the  text-book  can 
hope  to  accomplish  in  such  cases  is  to  give  as  clear  a  picture 
as  possible  of  the  tendencies  of  the  time. 

Some  critics  have  contended  that  only  those  facts  or  conclu- 
sions about  which  there  is  no  difference  of  opinion  should  be  pre- 
sented to  medical  students.  Those  who  are  acquainted  with 
the  subject,  however,  understand  that  books  written  from  this 
standpoint  contain  much  that  represents  the  uncertain  compromises 
of  past  generations,  and  that  the  need  of  revision  is  felt  as  fre- 
quently for  such  books  as  for  those  constructed  on  more  liberal 
principles.  There  does  not  seem  to  be  any  sound  reason  why  a 
text-book  for  medical  students  should  aim  to  present  only  those 
conclusions  that  have  crystallized  out  of  the  controversies  of  other 
times,  and  ignore  entirely  the  live  issues  of  the  day  which  are 


PREFACE.  5 

of  so  much  interest  and  importance  not  only  to  physiology,  but 
to  all  branches  of  medicine.  With  this  idea  in  mind  the  author 
has  endeavored  to  make  the  student  realize  that  physiology  is  a 
growing  subject,  continually  widening  its  knowledge  and  read- 
justing its  theories.  It  is  important  that  the  student  should 
grasp  this  conception,  because,  in  the  first  place,  it  is  true;  and, 
in  the  second  place,  it  may  save  him  later  from  disappointment 
and  distrust  in  science  if  he  recognizes  that  many  of  our  conclu- 
sions are  not  the  final  truth,  but  provisional  only,  representing 
the  best  that  can  be  done  with  the  knowledge  at  our  command. 
To  emphasize  this  fact  as  well  as  to  add  somewhat  to  the  interest 
of  the  reader  short  historical  resumes  have  been  introduced  from 
time  to  time,  although  the  question  of  space  alone,  not  to  men- 
tion other  considerations,  has  prevented  any  extensive  use  of  such 
material.  It  is  a  feature,  however,  that  a  teacher  might  develop 
with  profit.  Some  knowledge  of  the  gradual  evolution  of  our 
present  beliefs  is  useful  in  demonstrating  the  enduring  value  of 
experimental  work  as  compared  with  mere  theorizing,  and  also  in 
engendering  a  certain  appreciation  and  respect  for  knowledge 
that  has  been  gained  so  slowly  by  the  exertions  of  successive 
generations  of  able  investigators. 

A  word  may  be  said  regarding  the  references  to  literature 
inserted  in  the  book.  It  is  perfectly  obvious  that  a  complete 
or  approximately  complete  bibliography  is  neither  appropriate 
nor  useful,  however  agreeable  it  may  be  to  give  every  worker  full 
recognition  of  the  results  of  his  labors.  But  for  the  sake  of  those 
who  may  for  any  reason  wish  to  follow  any  particular  subject 
more  in  detail  some  references  have  been  given,  and  these  have 
been  selected  usually  with  the  idea  of  citing  those  works  which 
themselves  contain  a  more  or  less  extensive  discussion  and  litera- 
ture. Occasionally  also  references  have  been  made  to  works  of 
historical  importance  or  to  separate  papers  that  contain  the  experi- 
mental evidence  for  some  special  view. 


TABLE   OF  CONTENTS. 


SECTION  I. 
THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE. 

PAGE 

CHAPTER  I. — THE  PHENOMENON  OF  CONTRACTION 17 

The  Histological  Structure  of  the  Muscle  Fiber,  18. — Its  Appearance  by  Polarized 
Light,  19. — The  Extensibility  and  Elasticity  of  Muscular  Tissue,  20. — The  Inde- 
pendent Irritability  of  Muscle,  23. — Definition  and  Enumeration  of  Artificial  Stim- 
uli, 24. — The  Duration  of  the  Simple  Muscle  Contraction,  26. — The  Curve  of  a 
Simple  Muscle  Contraction,  26. — The  Latent  Period,  27. — The  Phases  of  Short- 
ening and  Relaxation,  27. — Isotonic  and  Isometric  Contractions,  28. — Maximal 
and  Submaximal  Contractions,  29. — Effect  of  Temperature  upon  the  Simple  Con- 
traction, 29. — Effect  of  Veratrin  on  the  Simple  Contraction,  31. — Contracture,  32. 
— Fatigue,  the  Treppe,  and  Effect  of  Rapidly  Repeated  Stimulation,  35. — The 
Wave  of  Contraction  and  Means  of  Measuring,  36. — Idiomuscular  Contractions, 
37. — The  Energy  Liberated  during  a  Muscular  Contraction,  37. — The  Propor- 
tional Amount  of  this  Energy  Utilized  in  Work,  38. — The  Curve  of  Work  and 
the  Absolute  Power  of  a  Muscle,  39. — Definition  of  Tetanus  or  Compound  Con- 
traction, 42. — The  Summation  of  Contractions,  44. — Discontinuity  of  the  Proc- 
esses of  Contraction  in  Tetanus,  44. — The  Muscle-tone,  44. — The  Rate  of  Stimu- 
lation Necessary  for  Complete  Tetanus,  45. — The  Tetanic  Nature  of  Voluntary 
Contractions,  46. — The  Ergograph,  48. — Results  of  Ergographic  Experiments, 
49. — Sense  of  Fatigue,  51. — Muscle  Tonus,  51. — Rigor  Mortis  and  Rigor  Ca- 
loris,  52. — The  Occurrence  and  Structure  of  Plain  Muscle  Tissue,  55. — Distinctive 
Properties  of  Plain  Muscle,  55. — The  General  Properties  of  Cardiac  Muscular 
Tissue,  57. — The  Contractility  of  Cilia  and  Their  General  Properties,  58. 

CHAPTER  II. — THE  CHEMICAL  COMPOSITION  OF  MUSCLE  AND  THE  CHEM- 
ICAL CHANGES  OF  CONTRACTION  AND  OF  RIGOR  MORTIS 60 

The  Composition  of  Muscle  Plasma,  60. — The  Proteins  of  Muscle,  60. — The 
Carbohydrates  of  Muscle,  62. — Lactic  Acid  in  Muscle,  63. — The  Nitrogenous  Ex- 
tractives of  Muscle,  63. — Pigments  of  Muscle,  64. — Enzymes  of  Muscle,  64. — Inor- 
ganic Constituents  of  Muscle,  64. — The  Chemical  Changes  in  Muscle  during 
Contraction,  65. — The  Chemical  Changes  during  Rigor  Mortis,  68. — The  Relation 
of  the  Waste  Products  to  Fatigue,  the  Chemical  Theory  of  Fatigue,  69. — Theories 
of  the  Mechanism  of  the  Contraction  of  Muscle,  71. 

CHAPTER   III. — THE   PHENOMENON   OF   CONDUCTION.    PROPERTIES   OF 

THE  NERVE  FIBER 75 

General  Statement  Regarding  Property  of  Conductivity,  75. — Structure  of 
the  Nerve  Fiber,  75.— Function  of  the  Myelin  Sheath,  76. — Chemistry  of  the 
Nerve  Fiber,  77. — The  Nerve  Trunk  an  Anatomical  Unit  Only,  77. — Definition 
of  Afferent  and  Efferent  Nerve  Fibers,  79. — Classification  of  Nerve  Fibers,  80. 
— The  Bell-Magendie  Law  of  the  Composition  of  the  Anterior  and  the  Posterior 
Roots  of  the  Spinal  Nerves,  81. — Cells  of  Origin  of  the  Anterior  and  Posterior 
Root  Fibers,  83. — Origin  of  the  Afferent  and  Efferent  Fibers  in  the  Cranial  Nerves, 
83. — Independent  Irritability  of  Nerve  Fibers,  Artificial  Nerve  Stimuli,  84. — 
Du  Bois-Reymond's  Law  of  Stimulation  by  the  Galvanic  Current,  86. — Electro- 
tonus,  87. — Pfliiger's  Law  of  Stimulation/  88. — The  Opening  and  the  Closing 
Tetanus,  90. — Mode  of  Stimulating  Nerves  in  Man,  90. — Motor  Points  of  Muscles, 
91. — Physical  and  Physiological  Poles,  93. 

CHAPTER  IV. — THE  ELECTRICAL  PHENOMENA  SHOWN  BY  NERVE  AND 

MUSCLE 95 

The  Demarcation  Current,  95. — Construction  of  the  Galvanometer,  97. — Con- 
struction of  the  Capillary  Electrometer,  100. — Non-polarizable  Electrodes,  100. — 
Action  Current  or  Negative  Variation,  102. — Mqnophasic  and  Diphasic  Action 
Currents,  103. — The  Rheoscopic  Frog  Preparation,  104. — Relation  of  Action 
Current  to  the  Contraction  Wave  and  Nerve  Impulse,  105. — The  Electrotonic 
Currents,  107. — The  Core-model,  108. 


8  TABLE    OF    CONTENTS. 

PAGE 

CHAPTER  V. — THE  NATURE  OF  THE  NERVE  IMPULSE  AND  THE  NUTRI- 
TIVE RELATIONS  OF  NERVE  FIBER  AND  NERVE  CELL 100 

Historical,  109. — Velocity  of  the  Nerve  Impulse,  110. — Relation  of  the  Nerve 
Impulse  to  the  Wave  of  Negativity,  112. — Direction  of  Conduction  in  the  Nerve, 
113.— Effect  of  Various  Influences  on  the  Nerve  Impulse,  114. — The  Refractory 
Period,  116. — The  Fatigue  of  Nerve  Fibers,  116. — The  Metabolism  of  the  Nerve 
Fiber  During  Functional  Activity,  118. — Theories  of  the  Nerve  Impulse,  119. — 
Qualitative  Differences  in  Nerve  Impulses,  121. — Doctrine  of  Specific  Nerve  Ener- 
gies, 121.— Nutritive  Relations  of  Nerve  Fibers  and  Nerve  Cells,  123.— Nerve 
Degeneration  and  Regeneration,  124. — Degenerative  Changes  in  the  Central 
End  of  the  Neuron,  126. 

SECTION  II. 
THE  PHYSIOLOGY  OF  THE  CENTRAL   NERVOUS  SYSTEM. 

CHAPTER  VI. — STRUCTURE  AND  GENERAL  PROPERTIES  OF  THE  NERVE 

CELL 129 

The  Neuron  Doctrine,  129. — The  Varieties  of  Neurons,  131. — Internal  Structure 
of  the  Nerve  Cell,  134.— General  Physiology  of  the  Nerve  Cell,  135.— Sum- 
mation of  Stimuli  in  Nerve  Cell,  138. — Response  of  the  Nerve  Cell  to  Varying 
Rates  of  Stimulation,  138. — The  Refractory  Period  of  the  Nerve  Cell,  139. 

"^CHAPTER  VII. — REFLEX  ACTIONS 140 

Definition  and  Historical,  140.— The  Reflex  Arc,  140.— The  Reflex  Frog,  142.— 
Spinal  Reflex  Movements,  142. — Theory  of  Co-ordinated  Reflexes,  144. — Spinal 
Reflexes  in  Mammals,  145. — Dependence  of  Co-ordinated  Reflexes  upon  the 
Excitation  of  the  Sensory  Endings,  145. — Reflex  Time,  146. — Inhibition  of  Re- 
flexes, 147. — Influence  of  the  Condition  of  the  Cord  on  Its  Reflex  Activities,  149. — 
Reflexes  from  Other  Parts  of  the  Nervous  System,  149. — Reflexes  Through  Periph- 
eral Ganglia,  Axon  Reflexes,  150. — The  Tonic  Activity  of  the  Spinal  Cord,  152. — 
Effects  of  the  Removal  of  the  Spinal  Cord,  153. — Knee-jerk,  155. — Reinforcement 
of  the  Knee-jerk,  155. — Is  the  Knee-jerk  a  Reflex  Act?  157. — Conditions  Influencing 
the  Extent  of  the  Knee-jerk,  159. — The  Knee-jerk  and  Spinal  Reflexes  as  Diagnos- 
tic Signs,  160.— Other  Spinal  Reflexes,  160. 

CHAPTER  VIII. — THE  SPINAL  CORD  AS  A  PATH  OF  CONDUCTION 162 

Arrangement  and  Classification  of  the  Nerve  Cells  in  the  Cord,  162. — General 
Relations  of  the  Gray  and  White  Matter  in  the  Cord,  164. — The  Methods  of 
Determining  the  Tracts  of  the  Cord,  164. — General  Classification  of  the  Tracts 
of  the  Cord,  165.— The  Names  and  Locations  of  the  Long  Tracts,  167.— The 
Termination  in  the  Cord  of  the  Fibers  of  the  Posterior  Root,  168. — Ascend- 
ing or  Afferent  Paths  in  the  Posterior  Funiculi,  169. — Ascending  or  Afferent 
Paths  in  the  Lateral  Funiculi,  172. — The  Spinal  Paths  for  the  Cutaneous  Senses 
•  (Touch,  Pain,  Temperature),  174. — The  Homolateral  or  Contralateral  Conduc- 

tion of  the  Cutaneous  Impulses,  176. — The  Descending  or  Efferent  Paths  in  the 
Anterolateral  Funiculi  (Pyramidal  System),  178. — Less  Well-known  Tracts  in  the 
Cord,  180. 

CHAPTER  IX. — THE  GENERAL  PHYSIOLOGY  OF  THE  CEREBRUM  AND  ITS 

MOTOR  FUNCTIONS 182 

The  Histology  of  the  Cortex,  183. — The  Classification  of  the  Systems  of  Fibers 
in  the  Cerebrum  (Projection,  Association,  and  Commissural),  184. — Physio- 

V  logical  Deductions  from  the  Histology  of  the  Cortex,  186. — The  Phenomenon  of 
Conditioned  Reflexes J 189. — Extirpation  of  the  Cerebrum,  190. — Localization  of 
Functions  in  the  Cerebrum,  Historical,  192. — The  Motor  Areas  of  the  Cortex,  196. 
— Differences  in  Paralysis  from  Injury  to  the  Spinal  Neuron  and  the  Pyramidal 
Neuron,  198.— Voluntary  Motor  Paths  Other  than  the  Pyramidal  Tract,  198.— 
The  Crossed  Control  of  the  Muscles  and  Bilateral  Motor  Representation  in  the 
Cortex,  199. — Are  the  Motor  Areas  Exclusively  Motor?  200. 

CHAPTER  X. — THE  SENSE  AREAS  AND  THE  ASSOCIATION  AREAS  IN  THE 

CORTEX 202 

The  Body-sense  Area,  203. — The  Course  of  the  Lemniscus,  205. — The  Center  for 
Vision,  207.— Histological  Evidence  of  the  Course  of  the  Optic  Fibers,  208.— 
The  Decussation  in  the  Chiasm,  209. — The  Projection  of  the  Retina  on  the  Oc- 
cipital Cortex,  210. — The  Function  of  the  Lower  Visual  Centers,  212. — The 
Auditory  Center,  212.— Course  of  the  Cochlear  Nerve,  214.— The  Physiological 
Significance  of  the  Lower  Auditory  Centers,  215. — Motor  Responses  from  the 
Auditory  Cortex,  216. — The  Olfactory  Center,  216. — The  Olfactory  Bulb  and 
its  Connections,  217.— The  Cortical  Center  for  Smell,  218.— The  Cortical  Center 
for  Taste,  218. — Aphasia,  219. — Sensory  Aphasia,  221. — The  Association  Areas, 
223. — Subdivision  of  the  Ass9ciation  Areas,  225. — The  Development  of  the 
Cortical  Areas,  226. — Histological  Differentiation  in  Cortical  Structure,  229. — 
Physiology  of  the  Corpus  Callosum.  230. — Physiology  of  the  Corpora  Striata 
and  Thalami,  231. 


TABLE  OF  CONTENTS.  9 

PAGE 

CHAPTER  XI. — THE  FUNCTIONS  OF  THE  CEREBELLUM,  THE  PONS,  AND 

THE  MEDULLA 233 

Anatomical  Structure  and  Relations  of  the  Cerebellum,  233. — General  State- 
ment of  Theories  Regarding  the  Cerebellum,  237. — Experiments  upon  Ablation 
of  the  Cerebellum,  239. — Interpretation  of  the  Experimental  and  Clinical  Re- 
sults, 240.-^-Conclusions  as  to  the  General  Functions  of  the  Cerebellum,  241. — 
The  Psychical  Functions  of  the  Cerebellum,  243. — Localization  of  Function  in 
the  Cerebellum,  243.— The  Functions  of  the  Medulla  Oblongata,  245.— The 
Nuclei  of  Origin  and  the  Functions  of  the  Cranial  Nerves,  246. 

CHAPTER  XII. — THE  SYMPATHETIC  OR  AUTONOMIC  NERVOUS  SYSTEM..  251 

^^  General  Statements,  251. — Autonomic  Nervous  System,  252. — The  Use  of  the 
Nicotin  Method,  253. — General  Course  of  the  Autonomic  Fibers  Arising  from 
the  Cord,  254.— General  Course  of  the  Fibers  Arising  from  the  Brain,  255. — 
General  Course  of  the  Fibers  Arising  from  the  Sacral  Cord,  256. — Normal  Mode 
of  Stimulation  of  Autonomic  Nerve  Fibers,  257. 

CHAPTER  XIII. — THE  PHYSIOLOGY  OF  SLEEP 258 

General    Statements,    258. — Physiological    Relations    during    Sleep,    258. — The 
Intensity  of  Sleep,  259. — Changes  in  the  Circulation  during  Sleep,  261. — Effect      • 
of  Sensory  Stimulation,  264. — Theories  of  Sleep,  265. — Hypnotic  Sleep,  269 

SECTION  in. 

THE  SPECIAL  SENSES. 
'     CHAPTER  XIV. — CLASSIFICATION  OF  THE  SENSES  AND  GENERAL  STATE- 

M  KXTS 271 

Classification  of  the  Senses,  271. — The  Doctrine  of  Specific  Nerve  Energies, 
273. — The  Weber-Fechner  Psychophysical  Law,  275. 

(/  CHAPTER  XV. — CUTANEOUS  AND  INTERNAL  SENSATIONS 278 

General  Classification,  278. — Protopathic,  Epicritic,  and  Deep  Sensibility,  278. — 
The  Punctiform  Distribution  of  the  Cutaneous  Senses,  280. — Specific  Nerve  Ener- 
gies of  the  Cutaneous  Nerves,  281. — The  Temperature  Senses,  282. — The  Sense  of 
Pressure,  283. — The  Threshold  Stimulus  and  the  Localizing  Power,  284. — The 
Pain  Sense,  286. — Localization  or  Projection  of  Pain  Sensations,  287. — Reflected 
or  Misreferred  Pains,  287. — Muscular  or  Deep  Sensibility,  288. — The  Quality  of  the 
Muscular  Sensibility,  289. — Sensations  of  Hunger  and  Thirst,  290.— The  Sense 
of  Thirst,  290. 

CHAPTER  XVI. — SENSATIONS  OF  TASTE  AND  SMELL 294 

The  Nerves  of  Taste,  294.— The  End-organ  of  the  Taste  Fibers,  296.— Classi- 
fication of  Taste  Sensations,  296. — Distribution  and  Specific  Energy  of  the  Fun- 
damental Taste  Sensations,  297. — Method  of  Sapid  Stimulation,  298. — The 
Threshold  Stimulus  for  Taste,  299. — The  Olfactory  Organ,  299. — The  Mech- 
anism of  Smelling,  300. — Nature  of  the  Olfactory  Stimulus,  301. — The  Qualities 
of  the  Olfactory  Sensations,  301. — Fatigue  of  the  Olfactory  Apparatus,  303. — 
Delicacy  of  the  Olfactory  Sense,  303. — Conflict  of  Olfactory  Sensations,  305. — 
Olfactory  Associations,  305. 

CHAPTER  XVII. — THE  EYE  AS  AN  OPTICAL  INSTRUMENT.     DIOPTRICS 

OF  THE  EYE 306 

Formation  of  an  Image  by  a  Biconvex  Lens,  306. — Formation  of  an  Image  in 
the  Eye,  309. — The  Inversion  of  the  Image  on  the  Retina,  311. — The  Size  of  the 
Retinal  Image,  312. — Accommodation  of  the  Eye,  313. — Limit  of  the  Power 
of  Accommodation  and  Near  Point  of  Distinct  Vision,  316. — Far  Point  of  Dis- 
tinct Vision,  316.— The  Refractive  Power  of  the  Surfaces  in  the  Eye,  317. — 
Optical  Defects  of  the  Normal  Eye,  319. — Spherical  Aberration,  319. — Abnor- 
malities in  the  Refraction  of  the  Eye,  Ametropia,  319. — Myopia,  320. — Hyper- 
metropia,  321. — Presbyopia,  321. — Astigmatism,  322. — Innervation  and  Control 
of  the  Ciliary  Muscle  and  the  Muscles  of  the  Iris,  324. — The  Accommodation 
Reflex  and  the  Light  Reflex,  326. — Action  of  Drugs  upon  the  Iris,  328. — The  Antag- 
onism of  the  Sphincter  and  Dilator  Muscles  of  the  Iris,  329. — Intra-ocular  Pressure, 
330. — The  Ophthalmoscope,  331. — Retinoscope,  333. — Ophthalmometer,  334. 

CHAPTER  XVIII. — THE  PROPERTIES  OF  THE  RETINA.     VISUAL  STIMULI 

AND  VISUAL  SENSATIONS 336 

The  Portion  of  the  Retina  Stimulated  by  Light,  336. — The  Action  Current  Caused 
by  Stimulation  of  the  Retina,  337. — The  Visual  Purple,  Rhodopsin,  338. — Extent 
of  the  Visual  Field,  Perimetrv,  340.— Central  and  Peripheral  Fields  of  Vision, 
342. — Visual  Acuity,  343. — Relation  Between  Stimulus  and  Sensation.  Thresh- 


10  TABLE    OF    CONTENTS. 

PAGE 

old  Stimulus,  345. — The  Light  Adapted  and  the  Dark  Adapted  Eye,  346. — 
Luminosity  or  Brightness,  347. — Qualities  of  Visual  Sensations,  349. — The  Achro- 
matic Series,  349. — The  Chromatic  Series,  350. — Color  Saturation  and  Color 
Fusion,  350. — The  Fundamental  Colors,  351. — The  Complementary  Colors, 
351.— After  Images,  Positive  and  Negative,  352.— Color  Contrasts,  353.— Color 
Blindness,  354. — Dichromatic  Vision,  355. — Tests  for  Color  Blindness,  356. 
— Achromatic  Vision,  357. — Distribution  of  Color  Sense  in  the  Retina,  357. — 
Functions  of  the  Rods  and  Cones,  358. — Theories  of-  Color  Vision,  360. — Entoptic 
Phenomena,  366. — Shadows  of  Corpuscles  and  Blood-vessels,  366. — Shadows 
from  Lens  and  Vitreous  Humor,  367. 

CHAPTER  XIX. — BINOCULAR  VISION 368 

Movements  of  the  Eyeballs,  368. — Co-ordination  of  the  Eye  Muscles,  Muscular 
Insufficiency  and  Strabismus,  370. — The  Binocular  Field  of  Vision,  372. — Corres- 
ponding or  Identical  Points,  372. — Physiological  Diplopia,  373. — The  Horopter, 
375. — Suppression  of  Visual  Images,  375. — Struggle  of  the  Visual  Fields,  375. — 
Judgments  of  Solidity,  376. — Monocular  Perspective,  376. — Binocular  Perspect- 
ive, 378. — Stereoscopic  Vision,  378. — Explana^n  of  Binocular  Perspective, 
380. — Judgments  of  Distance  and  Size,  381. — Optical  Deceptions,  382. 

CHAPTER  XX. — THE  EAR  AS  AN  ORGAN  FOR  SOUND  SENSATIONS 385 

The  Pinna  or  Auricle,  386. — The  Tympanic  Membrane,  386. — The  Ear  Bones, 
387. — Mode  of  Action  of  the  Ear  Bones,  388. — Muscles  of  the  Middle  Ear,  390. — 
The  Eustachian  Tube,  391. — Projection  of  the  Auditory  Sensations,  391. — 
Sensory  Epithelium  of  the  Cochlea,  392. — Nature  and  Action  of  the  Sound  Waves, 
393. — Classification  and  Properties  of  Musical  Sounds,  394. — Upper  Harmonics 
or  Overtones,  396. — Sympathetic  Vibrations  and  Resonance,  398. — Functions 
of  the  Cochlea,  398. — Sensations  of  Harmony  and  Discord,  402. — Limits  of 
Hearing,  402. 

CHAPTER  XXI. — FUNCTIONS  OF  THE  SEMICIRCULAR  CANALS  AND  THE 

VESTIBULE 404 

Position  and  Structure  of  the  Semicircular  Canals,  404. — Flouren's  Experi- 
ments upon  the  Semicircular  Canals,  405. — Temporary  and  Permanent  Effects 
of  the  Operations,  406.— Direct  Stimulation  of  the  Canals,  407.— Effect  of  Sec- 
tion of  the  Ampullary  or  the  Acoustic  Nerve,  408. — Is  the  Effect  of  Section  of 
the  Canals  due  to  Stimulation?  406. — Theories  of  the  Functions  of  the  Semicir- 
cular Canals,  409. — Summary  of  the  Views  upon  the  Function  of  the  Semicircular 
Canals,  411. — Functions  of  the  Utriculus  nd  Sacculus,  412. 

SECTION  IV. 
BLOOD  AND  LYMPH. 

CHAPTER  XXII. — GENERAL  PROPERTIES  OF  BLOOD.      PHYSIOLOGY  OF 

THE  CORPUSCLES 415 

Histological  Structure  of  Blood,  415. — Reaction  of  the  Blood,  416. — Specific 
Gravity  of  the  Blood,  420.— The  Red  Corpuscles,  421.— Condition  of  the  Hemo- 
globin in  the  Corpuscles,  421. — Hemolysis,  422. — Hemolysis  Due  to  Variations 
in  Osmotic  Pressure,  423. — Hemolysis  Due  to  Action  of  Hemolysins,  424. — 
Nature  and  Amount  of  Hemoglobin,  427. — Compounds  of  Hemoglobin  with 
Oxygen  and  Other  Gases,  429. — The  Iron  in  the  Hemoglobin,  430. — Crystals  of 
Hemoglobin,  431. — Absorption  Spectra  Hemoglobin  and  Oxyhemoglobin,  432. — 
Derivative  Compounds  of  Hemoglobin,  436. — Origin  and  Fate  of  the  Red  Cor- 
puscles, 438. — Variations  in  the  Number  of  Red  Corpuscles,  440. — Physiology  of 
the  Blood  Leucocytes,  443. — Variations  in  Number  of  the  Leucocytes,  444. — 
Functions  of  the  Leucocytes,  444. — Physiology  of  the  Blood  Plates,  445. 

CHAPTER  XXIII. — CHEMICAL  COMPOSITION  OF  THE  BLOOD  PLASMA; 
COAGULATION;  QUANTITY  OF  BLOOD;  REGENERATION  AFTER 
HEMORRHAGE 448 

Composition  of  the  Plasma  and  Corpuscles,  448. — Proteins  of  the  Blood  Plasma, 
450. — Serum  Albumin,  450. — Paraglobulin  (Serum  Globulin),  451. — Fibrino- 

fen,  451. — Less  Well-known  Proteins  of  the  Blood,  453. — Coagulation  of  Blood, 
53. — Time  of  Clotting,  455. — Preparation  of  Solutions  of  Fibrinogen,  456. — 
Preparation  of  Thrombin,  457. — The  Action  of  Thrombin  on  Fibrinogen,  459. — 
The  Influence  of  Calcium,  459. — The  Influence  of  Tissue-extracts,  460. — Theory  . 
of  Coagulation,  461. — Why  Blood  Does  not  Clot  Within  the  Vessels,  463. — 
Metathrombin,  464. — Intravascular  Clotting,  465. — Means  of  Hastening  or  of 
Retarding  Coagulation,  466. — Total  Quantity  of  Blood  in  the  Body,  469. — 
Regeneration  of  the  Blood  after  Hemorrhage,  470. — Blood  Transfusion,  472. 

CHAPTER  XXIV. — COMPOSITION  AND  FORMATION  OF  LYMPH 474 

General  Statements,  474. — Formation  of  Lymph,  476. — Lymphagogues  of  the 
First  Class,  477. — Lymphagogues  of  the  Second  Class,  478. — Summary  of  the 
Factors  Controlling  the  Flow  of  Lymph,  481.f 


TABLE  OF  CONTENTS.  11 


SECTION  V. 

PHYSIOLOGY  OF  THE  ORGANS  OF  CIRCULATION  OF  THE 
BLOOD  AND  LYMPH. 

PAGE 

CHAPTER  XXV. — THE  VELOCITY  AND  PRESSURE  OF  THE  BLOOD  FLOW.  .  .   483 

The  Circulation  as  Seen  Under  the  Microscope,  483. — The  Velocity  of  the  Blood 
Flow,  484. — Mean  Velocity  in  the  Arteries,  Veins,  and  Capillaries,  487.— Cause 
of  the  Variations  in  Velocity,  489. — Variations  of  Velocity  with  the  Heart  Beat 
or  Changes  in  the  Blood-vessels,  489.- — Time  Necessary  for  a  Complete  Cir- 
culation of  the  Blood,  490. — The  Pressure  Relations  in  the  Vascular  System,  491. — 
Methods  of  Recording  Blood-pressure,  491. — Systolic,  Diastolic,  and  Mean 
Arterial  Pressure,  495. — Method  of  Measuring  Systolic  and  Diastolic  Pressure 
in  Animals,  497. — Data  as  to  the  Mean  Pressure  in  Arteries,  Veins,  and  Capillaries, 
500. — Methods  of  Determining  Blood-pressure  in  the  Large  Arteries  of  Man, 
503. — Normal  Arterial  Pressure  in  Man  and  its  Variations,  508. — The  Method 
of  Determining  Venous  Pressures  *nd  Capillary  Pressures  in  Man,  509. 

CHAPTER  XXVI. — THE  PHYSICAL  FACTORS  CONCERNED  IN  THE  PRODUC- 
TION OF  BLOOD-PRESSURE  AND  BLOOD-VELOCITY 513 

Side  Pressure  and  Velocity  Pressure,  513. — The  Factors  Concerned  in  Producing 
Normal  Pressure  and  Velocity,  516. — General  Conditions  Influencing  Blood- 
pressure  and  Blood-velocity,  517. — The  Hydrostatic  Effect,  518. — Accessory 
Factors  Aiding  the  Circulation,  520.— The  Conditions  of  Pressure  and  Velocity 
in  the  Pulmonary  Circulation,  521. — Variations  of  Pressure  in  the  Pulmonary 
Circuit,  522. 

CHAPTER  XXVII.— THE  PULSE ' 523 

General  Statement,  523. — Velocity  of  the  Pulse  Wave,  524. — Form  of  the  Pulse 
Wave,  Sphygmography,  526. — Explanation  of  the  Catacrotic  Waves,  528. — 
Anacrotic  Waves,  529.— The  Kinds  of  Pulse  in  Health  and  Disease,  530.— Venous 
Pulse,  531. 

CHAPTER  XXVIII.— THE  HEART  BEAT 537 

General  Statement,  537. — Musculature  of  the  Auricles  and  Ventricles,  537. — 
The  Auriculoventricular  Bundle,  540. — The  Sequence  of  the  Heart-beat,  544. — 
The  Electrical  Variation,  545.— Change  of  Form  during  Systole,  547.— The 
Apex  Beat,  549. — Cardiogram,  550. — Intraventricular  Pressure  during  Sys- 
tole, 551. — The  Volume  Curve  and  the  Ventricular  Output,  553. — The  Heart 
Sounds,  556. — The  Third  Heart  Sound,  558. — Events  Occurring  during  a  Cardiac 
Cycle,  559. — Time  Relations  of  Systole  and  Diastole,  560. — Normal  Capacity 
of  Ventricle  and  Work  Done  by  the  Heart,  561. — Coronary  Circulation  during 
the  Heart  Beat,  563. — Suction-pump  Action  of  the  Heart,  564. — Occlusion  of  the 
Coronary  Vessels,  565. — Fibrillar  Contractions  of  Heart  Muscle,  566. 

CHAPTER  XXIX. — THE  CAUSE  AND  THE  SEQUENCE  OF  THE  HEART  BEAT. 

PROPERTIES  OF  THE  HEART  MUSCLE 568 

General  Statement,  568. — The  Neurogenic  Theory  of  the  Heart  Beat,  570. — 
Myogenic  Theory,  571. — Automaticity  of  the  Heart,  573. — Action  of  Calcium, 
Potassium,  and  Sodium  Ions  on  the  Heart,  574. — Connection  of  Inorganic  Salts 
with  the  Causation  of  the  Beat,  576. — Maximal  Contractions  of  the  Heart,  577. — 
Refractory  Period  of  the  Heart  Beat,  579.— The  Compensatory  Pause,  580.— 
Normal  Sequence  of  the  Heart  Beat,  580. — Tonicity  of  the  Heart  Muscle,  583. 

CHAPTER  XXX. — THE  CARDIAC    NERVES  AND  THEIR   PHYSIOLOGICAL 

ACTION 585 

Course  of  the  Cardiac  Nerves,  585. — Action  of  the  Inhibitory  Fibers,  585. — 
Analysis  of  the  Inhibitory  Action,  587. — Effect  of  Vagus  on  the  Auricle  and 
the  Ventricle,  589. — Escape  from  Inhibition,  589. — Reflex  Inhibition  of  the 
Heart  Beat,  the  Cardio-inhibitory  Center,  590.— The  Tonic  Activity  of  the 
Cardio-inhibitory  Center,  591. — The  Action  of  Drugs  on  the  Inhibitory  Appara- 
tus, 593. — The  "Nature  of  Inhibition,  593. — Course  of  the  Accelerator  Fibers, 
595. — Action  of  the  Accelerator  Fibers,  597. — Tonicity  of  the  Accelerators  and 
Reflex  Acceleration,  597. — The  Accelerator  Center,  599. 

CHAPTER  XXXI. — THE  RATE  OF  THE  HEART  BEAT  AND  ITS  VARIATIONS 

UNDER  NORMAL  CONDITIONS 600 

Variations  in  Rate  with  Sex,  Size,  and  Age,  600.— Variations  through  the  Extrinsic 
Cardiac  Nerves,  601. — Variations  with  Blood-pressure,  601. — WTith  Muscular 
Exercise,  602. — With  the  Gases  of  the  Blood,  603. — With  Temperature  of  the 
Blood,  603. 


12  TABLE    OF    CONTENTS. 

PAGE 

CHAPTER  XXXII.— THE  VASOMOTOR  NERVES  AND  THEIR  PHYSIOLOGICAL 

ACTIVITY 606 

Historical,  606. — Methods  Used  to  Determine  Vasomotor  Action,  607. — The 
Plethysmograph,  608. — General  Distribution  and  Course  of  the  Vasoconstrictof 
Nerve  Fibers,  610. — Tonic  Activity  of  the  Vasoconstrictors,  613. — The  Vaso- 
constrictor Center,  613. — Vasoconstrictor  Reflexes,  Pressor  and  Depressor  Fibers, 
615. — Depressor  Nerve  of  the  Heart,  618. — Vasoconstrictor  Centers  in  the  Spinal 
Cord,  619. — Rhythmical  Activity  of  the  Vasoconstrictor  Center,  619. — Course 
and  Distribution  of  the  Dilator  Fibers,  620. — General  Properties  of  Vasodilator 
Fibers,  621.— Vasodilator  Center  and  Reflexes,  622. — Vasodilatation  Due  to 
Afferent  Fibers,  623. — Regulation  of  the  Blood-supply  by  Chemical  and  Mechan- 
ical Stimuli,  624. 

CHAPTER    XXXIII. — THE    VASOMOTOR    SUPPLY    OF    THE    DIFFERENT 

ORGANS 626 

Vasomotors  of  the  Heart,  626.-t— Vasonwtors  of  the  Pulmonary  Arteries,  627. — 
Circulation  in  the  Brain  and  Its  Regulation,  628. — Arterial  Supply,  t'.^s.  Venous 
Supply,  629. — The  Meningeal  Spaces,  630. — Intracranial  Pressure,  632. — Effect 
of  Changes  in  Arterial  Pressure  upon  the  Blood  Flow  through  the  Brain,  634. — 
The  Regulation  of  the  Brain  Circulation,  636. — Vasomotor  .serves  of  the  Head 
Region,  638. — Of  the  Trunk  and  the  Limbs,  639. — Of  the  Abdominal  Organs,  ' 
640. — Of  the  Genital  Organs,  640. — Of  the  Skeletal  Muscles,  641. — The  Vaso- 
motor  Nerves  to  the  Veins,  642. — The  Circulation  of  the  Lymph,  642. 

SECTION  VI. 
PHYSIOLOGY  OF  RESPIRATION. 

CHAPTER  XXXIV. — HISTORICAL  STATEMENT.     THE  ORGANS  OF  EXTER- 
NAL RESPIRATION  AND  THE  RESPIRATORY  MOVEMENTS 6-14 

Historical,  644. — Anatomy  of  Organs  of  Respiration,  648. — Thorax  as  a  Closed 
Cavity,  648. — Normal  Position  of  the  Thorax,  649. — Inspiration  by  Contraction 
of  the  Diaphragm,  650. — Inspiration  by  Elevation  of  the  Ribs,  651. — The  Muscles 
of  Inspiration,  652. — Muscles  of  Expiration,  652. — Quiet  and  Forced  Respiratory 
Movements,  Eupnea  and  Dyspnea,  653. — Costal  and  Abdominal  Types  of  Res- 
piration, 654.— Accessory  Respiratory  Movements,  655. — Registration  of  the 
Respiratory  Movements,  655.— Volumes  of  Air  Respired,  Vital  Capacity,  Tidal 
Air,  Complemental  Air,  Supplemental  Air,  Residual  Air,  Minimal  Air,  657. — 
Size  of  the  Bronchial  Tree,  658.— Artificial  Respiration,  659. 

CHAPTER  XXXV. — THE    PRESSURE    CONDITIONS  IN  THE   LUNGS  AND 

THORAX  AND  THEIR  INFLUENCE  UPON  THE  CIRCULATION..,.  .  .  .  661 

The  Intrapulmonic  Pressure  and  Its  Variations,  661. — Intrathoracic  Pressure, 
662. — Variations  of,  with  Forced  and  Unusual  Respirations,  663.— Origin  of 
the  Negative  Pressure  in  the  Thorax,  664. — Pneumothorax,  665. — Aspiratory 
Action  of  the  Thorax,  665. — Respiratory  Waves  of  Blood-pressure,  666. 

CHAPTER  XXXVI. — THE  CHEMICAL  AND  PHYSICAL  CHANGES  IN  THE  AIR 

AND  THE  BLOOD  CAUSED  BY  RESPIRATION 669 

The  Inspired  and  Expired  Air,  669. — Physical  Changes  in  the  Expired  Air,  670. 
— Injurious  Action  of  Expired  Air,  670. — Ventilation,  672. — The  Gases  of  the 
Blood,  674. — The  Pressure  of  Gases,  677. — Absorption  of  Gases  in  Liquids, 
678. — The  Tension  of  Gases  in  Solution,  679. — The  Condition  of  Nitrogen  in 
the  Blood,  681.— Condition  of  Oxygen  in  the  Blood,  681.— Condition  of  Carbon  Di- 
oxid  in  the  Blood,  684. — The  Physical  Theory  of  Respiration,  685. — Gaseous 
Exchanges  in  the  Lungs,  686. — Exchange  of  Gases  in  the  Tissues,  688. — Secre- 
tory Activity  of  Lungs,  689. 

CHAPTER  XXXVII. — INNERVATION  OF  THE  RESPIRATORY  MOVEMENTS..  .  691 

The  Respiratory  Center,  691. — Spinal  Respiratory  Centers,  692. — Automatic 
Activity  of  the  Respiratory  Center,  693. — Reflex  Stimulation  of  the  Center, 
694. — Afferent  Relations  of  the  Vagus  to  the  Center,  695. — The  Inspiratory 
and  Inhibitory  Fibers  of  the  Vagus,  697. — Respiratory  Reflexes  from  the  Larynx, 
Pharnyx,  and  Nose,  699. — Voluntary  Control  of  the  Respiratory  Movements, 
699. — Nature  of  the  Respiratory  Center,  700. — Respiratory  Centers  in  the  Mid- 
brain,  701. — Automatic  Stimulus  to  the  Respiratory  Center,  701. — Cause  of  the 
First  Respiratory  Movements,  705. — Dyspnea,  Hyperpnea,  and  Apnea,  706. — 
Innervation  of  the  Bronchial  Musculature,  709. 

CHAPTER  XXXVIII. — THE  INFLUENCE  OF  VARIOUS  CONDITIONS  UPON 

THE  RESPIRATION 710 

Effect  of  Muscular  Work  on  the  Respiratory  Movements,  710. — Effect  of  Varia- 
tions in  the  Composition  of  the  Air,  711. — High  and  Low  Barometric  Pressures, 
Mountain  Sickness,  Caisson  Disease,  713. — The  Respiratory  Quotient  and  Its 
Variations,  714. — Modified  Respiratory  Movements,  716. 


c 


TABLE   OF    CONTENTS.  13 

SECTION  VII. 

PHYSIOLOGY  OF  DIGESTION  AND  SECRETION.         PAGE 
CHAPTER  XXXIX. — MOVEMENTS  OF  THE  ALIMENTARY  CANAL 719 

Mastication,  719.— Deglutition,  719.— Nervous  Control  of  Deglutition,  722.— 
Cardiac  Sphincter,  724. — Anatomy  of  the  Stomach,  725. — Musculature  of  the 
Stomach,  726. — Movements  of  the  Stomach,  726. — Effect  of  the  Nerves  on  the 
Movements  of  the  Stomach,  730. — Hunger  Contractions,  731. — Movements  of 
the  Intestines,  731. — Peristaltic  and  Pendular  Movements  of  the  Intestines,  734. — 
Movements  of  the  Intestinal  Villi,  735. — Nervous  Control  of  the  Intestinal  Move- 
ments, 736. — Effect  of  Various  Conditions  on  the  Intestinal  Movements,  736. — 
Movements  of  the  Large  Intestines,  737. — Defecation,  739. — Vomiting,  741. — 
Nervous  Mechanism  of  Vomiting,  742. 

CHAPTER  XL. — GENERAL  CONSIDERATION  OF  THE  COMPOSITION  OF  THE 

FOOD    AND    THE    ACTION    OF    ENZYMES 744 

Foods  and  Food-stuffs,   744. — Accessory  Articles  of  Diet,   747. — Enzymes,  His-  '\ 

torical,  747. — Reversible  Reactions,  750. — Specificity  of  Enzymes,  751. — Defini- 
tion and  Classification  of  Enzymes,  752. — General  Properties  of  Enzymes,  754. — 
Partial  List  of  Enzymes,  756. — Chemical  Composition  of  the  Enzymes,  757. 

CHAPTER  XLI. — THE  SALIVARY  GLANDS  AND  THEIR  DIGESTIVE  ACTION  758 

Anatomy  of  the  Salivary  Glands,  758. — Histological  Structure,  760. — Com- 
position of  the  Secretion,  761. — The  Secretory  Nerves,  761. — Trophic  and  Secre- 
tory Nerve  Fibers,  764. — Histological  Changes  during  Activity,  765. — Action  of 
Drugs  upon  the  Secretory  Nerves,  768. — Paralytic  Secretion,  769. — Normal 
Mechanism  of  Salivary  Secretion,  769. — Electrical  Changes  in  Glands,  771. — 
Digestive  Action  of  Saliva,  Ptyalin,  771. — Conditions  Influencing  the  Action 
of  Ptyalin,  773. — Functions  of  the  Saliva,  773. 

CHAPTER  XLII. — DIGESTION  AND  ABSORPTION  IN  THE  STOMACH .   774 

Structure  of  the  Gastric  Glands,  774. — Histological  Changes  during  Secretion, 
775. — Method  of  Obtaining  the  Gastric  Secretion  and  Its  Normal  Composition, 
776.— The  Acid  of  Gastric  Juice,  778.— Origin  of  HC1,  779.— Secretory  Nerves 
of  the  Gastric  Glands,  780. — Normal  Mechanism  of  the  Secretion  of  the  Gastric 
Juice,  781.— Nature  and  Properties  of  Pepsin,  784.— Artificial  Gastric  Juice,  785. 
— Pepsin-hydrochloric  Digestion,  786. — The  Rennin  Enzyme,  788. — Digestive 
Changes  in  the  Stomach,  790.— Absorption  in  the  Stomach,  791. 

CHAPTER  XLIII. — DIGESTION  AND  ABSORPTION  IN  THE  INTESTINES.  .  . .  793 

Structure  of  the  Pancreas,  793. — Composition  of  the  Secretion,  794. — Secre- 
tory Nerve  Fibers  to  the  Pancreas,  794. — The  Curve  of  Secretion,  795. — Nor- 
mal Mechanism  of  Pancreatic  Secretion,  796. — Secretin,  796. — Enterokinase, 
797. — Digestive  Action  of  Pancreatic  Juice,  798. — The  Amino-acids,  799. — Signifi- 
cance of  Tryptic  Digestion,  801. — Action  of  the  Diastatic  Enzyme  (Amylase),  802. 
— Action  of  the  Lipolytic  Enyzme  (Lipase,  Steapsin),  803. — The  Intestinal  Secre- 
tion (Succus  Entericus),  804. — Absorption  in  the  Small  Intestine,  806. — Absorp- 
tion of  Carbohydrates,  808. — Absorption  of  Fats,  809. — Absorption  of  Proteins, 
811. — Digestion  and  Absorption  in  the  Large  Intestine,  812. — Bacterial  Action  in 
the  Small  Intestine,  813. — Bacterial  Actipn  in  the  Large  Intestine,  814. — Physio- 
logical Importance  of  Intestinal  Putrefaction,  815. — Composition  of  the  Feces,  816 

CHAPTER  XLIV. — PHYSIOLOGY  OF  THE  LIVER  AND  SPLEEN 818 

Structure  of  the  Liver,  818.— Composition  of  Bile,  818.— The  Bile  Pigments, 
820. — The  Bile  Acids,  821. — Cholesterin,  823. — Lecithin,  Fats,  and  Nucleo- 
albumins,  824. — Secretion  of  the  Bile,  824. — Ejection  of  the  Bile — Function  of 
the  Gall-bladder,  826.— Occulsion  of  the  Bile-ducts,  827.— Physiological  '  Im- 
portance of  Bile,  828. — Occurrence  of  Glycogen,  829. — Origin  of  Glycogen,  830. 
— Function  of  Glycogen,  Glycogenic  Theory,  832. — Glycogen  in  the  Muscles 
and  Other  Tissue,  834. — Conditions  Affecting  the  Supply  of  Glycogen,  835. — 
Formation  of  Urea  in  the  Liver,  835. — Physiology  of  the  Spleen,  836. 

CHAPTER  XLV. — THE  KIDNEY  AND  SKIN  AS  EXCRETORY  ORGANS 839 

Structure  of  the  Kidney,  839. — The  Secretion  of  Urine,  840. — Function  of  the 
Glomerulus,  842. — Function  of  the  Convoluted  Tubule,  844. — Action  of  Diu- 
retics, 846. — The  Blood  Flow  Through  the  Kidneys,  847. — Hormone  Stimulation, 
849. — The  Composition  of  Urine,  850. — The  Nitrogenous  Excreta  in  the  Urine, 
,  851. — Origin  and  Significance  of  Urea,  853.-y-Origin  and  Significance  of  the 
Purin  Bodies  (Uric  Acid,  Xanthin,  Hypoxanthin),  856. — Origin  and  Significance 
of  the  Creatinin  and  Creatin,  859. — Hippuric  Acid,  860. — The  Conjugated  Sul- 
phates and  the  Sulphur  Excretion,  861.— Secretion  of  the  Water  and  Inorganic 
Salts,  862.— Micturition,  863.— Contractions  of  the  Bladder.  864.— Nervous 
Mechanism  of  Micturition,  866. — Excretory  Functions  of  the  Skin,  867. — Com- 
position of  Sweat,  867. — Secretory  Fibers  of  Sweat  Glands,  869. — Sweat  Centers, 
870. — Sebaceous  Secretion,  871. — Excretion  of  Carbon  Dioxid  through  the  Skin, 
872. 


14  TABLE  OF  CONTENTS. 

PAGE 

CHAPTER   XLVI. — SECRETION   OF  THE   DUCTLESS    GLANDS — INTERNAL 

SECRETION 873 

Internal  Secretion  of  Liver,  874. — Internal  Secretion  of  the  Thyroid  Tissues, 
874. — Extirpation  of  Thyroids  and  Parathyroids,  875. — Function  of  the  Para- 
thyroids, 876. — Function  of  the  Thyroid,  879. — Function  of  Thymus,  880. — 
Structure  and  Properties  of  Adrenal  Bodies,  881. — Physiology  of  the  Medulla, 
882. — Epinephrin,  883. — The  Chromaffin  Tissues,  883. — Secretory  Nerves  of  the 
Adrenal  Gland,  886.— Functional  Significance  of  the  Medullary  Tissue,  886. — 
Functional  Significance  of  Cortical  Tissue,  887. — Pituitary  Body,  888.— The 
Pineal  Body,  892. — Internal  Secretion  of  Testis  and  Ovary,  893. — Internal  Secre- 
tion of  Pancreas,  896. 

SECTION  VIII. 
NUTRITION  OF  HEAT  PRODUCTION  AND  REGULATION. 

CHAPTER  XLVII. — GENERAL    METHODS.      HISTORY   OF  THE   PROTEIN 

FOOD 899 

General  Statement,  899.— Nitrogen  Equilibrium,  899.— Carbon  Equilibrium 
and  Body  Equilibrium,  901. — Balance  Experiments,  901. — Respiration  Cham- 
ber, 901. — Effect  of  Non-protein  Food  on  Nitrogen  Equilibrium,  902. — Nutritive 
History  of  the  Protein  Food,  903.— Tissue  Protein  and  Circulating  Protein,  904.— 
Amount  of  Protein  Necessary  in  Normal  Nutrition,  906. — Nutritive  Value  of 
Different  Proteins,  909. — The  Unknown  Accessories  (Vitamines),  912. — Specific 
Dynamic  Action  of  Proteins,  914. 


CHAPTER  XLVIII. — NUTRITIVE  HISTORY  OF  CARBOHYDRATES  AND  FATS.  915 

te  Supply  of  the  Body,  915. — Intermediary  Metabolism  of  the 
the  Body,  916. — Regulation  of  the  Sugar  Supply  of  the  Body, 
919. — Functions  of  the  Carbohydrate  Food,  922. — Nutritive 


The  Carbohydrate  Supply  of  the  Body,  915.— Intermediary  Metabolism  of  the 
Carbohydrate  in  the  Body,  916. — Regulation  of  the  Sugar  Supply  of  the  Body, 
918.— Diabetes,  919.— Functions  of  the  Carbohydrate  Food,  922.— Nutritive 
Value  of  Fats,  924. — Intermediary  Metabolism  of  Fats,  924. — Origin  of  Body 
Fat,  926. — Origin  of  Body  Fat  from  Food  Fat,  927. — Origin  of  Body  Fat  from 
Carbohydrates,  927. — Source  of  Fat  in  Ordinary  Diets,  928. — Cause  of  the  Forma- 
tion of  Fat,  Obesity,  928. 


CHAPTER  XLIX. — NUTRITIVE  VALUE  OF  THE  INORGANIC  SALTS  AND  THE 

ACCESSORY  ARTICLES  OF  DIET 931 

The  Inorganic  Salts  of  the  Body,  931. — Effect  of  Ash-free  and  Ash-poor  Diets, 
932. — Special  Importance  of  Sodium  Chlorid,  Calcium,  and  Iron  Salts,  932. — 
The  Condiments,  Flavors,  and  Stimulants,  935. — Physiological  Effects  of  Alcohol, 
936. 

CHAPTER  L. — EFFECT  OF  MUSCULAR  WORK  AND  TEMPERATURE  ON  BODY 

METABOLISM;  HEAT  ENERGY  OF  FOODS;  DIETETICS 942 

The  Effect  of  Muscular  Work,  942.— Effect  of  Sleep,  944.— Effect  of  Variations 
in  Temperature,  944. — Effect  of  Starvation,  945. — The  Potential  Energy  of 
Food,  946.— Dietetics,  950. 

CHAPTER  LI. — THE  PRODUCTION  OF  HEAT  IN  THE  BODY;  ITS  MEASURE- 
MENT AND  REGULATION;  BODY  TEMPERATURE;  CALORIMETRY; 
PHYSIOLOGICAL  OXIDATIONS 957 

Historical  Account  of  Theories  of  Animal  Heat,  957. — Body  Temperature  in 
Man,  958. — Calorimetry,  960. — Respiration  Calorimeter,  963. — Heat  Regulation, 
967. — Regulation  of  Heat  Loss,  967. — Regulation  of  Heat  Production,  969. — 
Existence  of  Heat  Centers  and  Heat  Nerves,  971.— Theories  of  Physiological 
Oxidations,  973. 

SECTION  IX. 

PHYSIOLOGY  OF  REPRODUCTION. 
CHAPTER  LII. — PHYSIOLOGY  OF  THE  FEMALE  REPRODUCTIVE  ORGANS.  . .  981 

General  Statement,  981. — The  Graafian  Follicle  and  the  Corpus  Luteum,  981. — 
Menstruation  and  Puberty,  983. — Structural  Changes  in  the  Uterus  during 
Menstruation,  984. — The  Phenomenon  of  Heat  in  Lower  Animals,  984. — The 
Relation  of  the  Ovaries  to  Menstruation,  985. — Physiological  Significanec  of 
Menstruation,  987. — Effect  of  the  Menstrual  Cycle  on  Other  Functions,  988. — 
Passage  of  the  Ovum  into  the  Uterus,  989. — Maturation  of  the  Ovum,  990. — 
Fertilization  of  the  Ovum,  992. — Implantation  of  the  Ovum,  994. — Nutrition  of  the 
Ovum — Physiology  of  the  Placenta,  995. — Changes  in  the  Maternal  Organism 
during  Pregnancy,  997. — Parturition,  998. — The  Mammary  Glands,  999. — Con- 
nection between  the  Uterus  and  the  Mammary  Glands,  999. — Composition  of 
Milk,  1001. 


TABLE    OF    CONTENTS.  15 

PAGE 

CHAPTER  LIII. — PHYSIOLOGY  OF  THE  MALE  REPRODUCTIVE  ORGANS  .  .  1003 

Sexual  Life  of  Male,  1003. — Properties  of  the  Spermatozoa,  1004. — Chemistry 
of  the  Spermatozoa,  1006. — The  Act  of  Erection,  1007. — Reflex  Apparatus  of 
Erection  and  Ejaculation,  1008. 

CHAPTER   LIV. — HEREDITY;    DETERMINATION    OF   SEX;    GROWTH    AND 

SENESCENCE 1010 

Definition  of  Heredity,  1010. — Evolution  and  Epigenesis,  1010. — Theory  of  Mu- 
tations, 1012. — The  Mendelian  Law,  1013. — Determination  of  Sex,  1015. — 
Growth  and  Senescence,  1017. 


APPENDIX. 

I. — PROTEINS  AND  THEIR  CLASSIFICATION 1025 

Definition  and  General  Structure  of  Proteins,  1025.— Reactions  of  Proteins,  1027. 
— Classification  of  Proteins,  1029. — The  Albumins,  1029. — The  Globulins,  1030. 
•—The  Glutelins,  1030. — Alcohol-soluble  Proteins  (Prolamines),  1030. — Albumin- 
oids, 1030.— Protamins  and  Histons,  1030.— The  Conjugated  Proteins,  1031.— 
The  Derived  Proteins,  1032. 

II. — DIFFUSION  AND  OSMOSIS 1032 

Diffusion,  Dialysis,  and  Osmosis,  1032. — Osmotic  Pressure,  1033. — Electrolytes, 
1034.— Gram-molecular  Solutions,  1034.— Calculation  of  Osmotic  Pressure  in 
Solutions,  1035. — Determination  of  Osmotic  Pressure  by  the  Freezing  Point, 
1035. — Application  to  Physiological  Processes,  1036. — Osmotic  Pressure  of  Pro- 
teins, 1036. — Isotonic,  Hypertonic,  and  Hypnotonic  Solutions,  1036. — Diffusion  or 
Dialysis  of  Soluble  Constituents,  1037. — Diffusion  of  Proteins,  1037. 

INDEX  . .  . .  1039 


A  TEXT-BOOK 


OF 


PHYSIOLOGY 


SECTION  I. 
THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE. 


CHAPTER  I. 
THE  PHENOMENON  OF  CONTRACTION. 

The  tissues  in  the  mammalian  body  in  which  the  property  of 
contractility  has  been  developed  to  a  notable  extent  are  the  mus- 
cular and  the  ciliated  epithelial  cells.  The  functional  value  of  the 
muscles  and  the  cilia  to  the  body  as  an  organism  depends,  in  fact, 
upon  the  special  development  of  this  property.  The  muscular 
tissues  of  the  body  fall  into  three  large  groups,  considered  from 
either  a  histologicalor  a  functional  standpoint, — namely,  the  striated 
skeletal  muscle,  the  striated  cardiac  muscle,  and  the  plain  muscle. 
These  tissues  exhibit  certain  marked  differences  in  properties  which 
are  described  farther  on.  In  each  group,  moreover,  there  are 
certain  minor  differences  in  structure  which  are  associated  with 
differences  in  properties;  thus,  skeletal  muscle  from  different  re- 
gions of  the  same  animal  may  show  variations  in  rapidity  of 
contraction,  and  this  variation  goes  hand  in  hand  with  an  obvious 
difference  in  histological  structure.  Similar,  perhaps  more 
marked,  differences  are  observed  in  the  plain  muscular  tissue  of 
various  organs.  The  muscular  tissues  from  animals  belonging  to 
different  classes  exhibit  naturally  even  wider  variations  in  proper- 
ties, and  these  differences  in  some  cases  are  not  associated  with 
visible  variations  in  structure. 

The  Structure  of  Skeletal  Muscle. — This  tissue  makes  up  the 
essential  part  of  the  skeletal  muscles  by  means  of  which  our 
2  17 


18 


THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE. 


voluntary  movements  are  effected.  What  we  call  a  muscle  is  an 
organ  composed  of  many  thousands  of  muscle  fibers,  bound  to- 
gether by  connective  tissue,  and  surrounded  by  a  sheath  of  the 
same  tissue.  Each  fiber  is  a  minute  cylindrical  or  prismatic 
thread,  whose  diameter  varies  perhaps  between  0.1  and  0.01  mm., 
and  whose  length  does  not  exceed  36  mm.  It  constitutes  the  unit 
of  structure  of  the  muscle,  and  the  shortening  of  the  muscle,  as  a 
whole,  is  the  expression  of  the  combined  effect  of  the  contractions 
of  the  constituent  fibers.  In  considering  the  physiology  of  the 
muscle  as  a  contracting  mechanism  it  is  convenient  to  discuss  the 
phenomenon  as  it  occurs  in  a  single  fiber.  As  a  matter  of  fact, 
each  fiber  is  a  complex  structure,  consisting  of  several  distinct 
parts.  It  is  developed  from  a  single  cell,  and  since  it  contains  a 
number  of  nuclei,  we  may  regard  it  histologically  as  a  sort  of  a 
multinuclear  giant  cell  of  elongated  form.  Each  fiber  is  enclosed 
within  a  thin,  structureless,  elastic  membrane,  the  sarcolemma. 
The  material  of  the  fiber  inside  the  sarcolemmal  bag  shows  the 
characteristic  cross-striation,  and  is  supposed  to  be  of  a  semi- 
liquid  or  viscous  consistency  when  living.  This  material,  as  a 
whole,  is  designated  as  the  muscle  plasma. 

There  is  on  record  an  interesting  observation  by  Kiihne*  which  seems 
to  demonstrate  the  fluid  nature  of  the  living  muscle  substance.  He  hap- 
pened, on  one  occasion,  to  find  a  frog's  muscle  fiber  containing  a  nematode 
worm  within  the  sarcolemma.  The  animal  swam  readily  from  one  end  of 
the  fiber  to  the  other,  pushing  aside  the  cross  bands,  which  fell  into  place 


Fig.  1. — A  cross-section  of  muscle 
fiber  of  rabbit.  The  bundles  of  fibrils  are 
dark;  the  intervening  small  amount  of 
sarcoplasm  is  represented  by  the  clear 
spaces. — (Kolliker.) 


Fig.  2. — Cross-section  of  two  muscle 
fibers  of  the  fly:  Ms,  The  columns  of 
fibrils;  Sp,  the  sarcoplasm. — (Schieffer- 
decker.) 


again  after  the  animal  had  passed.  At  one  end,  where  the  fiber  had  been 
injured,  the  worm  was  unable  to  force  its  way.  The  muscle  substance  at 
this  point  was  dead  and  apparently  had  passed  into  a  solid  condition.  The 
fact  that  the  cross  bands  were  displaced  only  temporarily  by  the  movement 
and  fell  back  into  their  normal  position  would  indicate  that  they  may  have 
a  more  solid  structure. 

*  Kiihne,  "Archiv  fur  pathologische  Anatomic,"  26,  222,  1863. 


THE    PHENOMENON    OF    CONTRACTION. 


19 


Disregarding  the  nuclei,  the  muscle  plasma  consists  of  two 
different  structures :  the  fibrils,  which  are  long  and  thread-like  and 
run  the  length  of  the  fiber,  and  the  inter- 
vening sarcoplasm.  The  fibrils  consist  of 
alternating  dim  and  light  discs  or  segments, 
which,  falling  together  in  the  different  fibrils, 
give  the  cross-striation  that  is  character- 
istic. In  mammalian  muscles  the  fibrils  are 
grouped  more  or  less  distinctly  into  bundles 
or  columns  (sarcostyles) ,  between  which  lies 
the  scanty  sarcoplasm.  The  relative  amount 
of  sarcoplasm  to  fibrillar  substance  varies 
greatly  in  the  striped  muscles  of  different 
animals,  as  is  indicated  in  the  accompanying 
illustrations.  The  evidence  from  compara- 
tive physiology  indicates  that  the  fibrils  are 
the  contractile  element  of  the  fiber,  while 
the  sarcoplasm,  it  may  be  assumed,  pos- 
sesses a  general  nutritive  function.  Among 
mammals  there  are  certain  muscles  in  which 
the  amount  of  sarcoplasm  within  each  fiber 
is  relatively  large,  and  this  sarcoplasm, 
having  the  granular  structure  common  to 
undifferentiated  protoplasm,  interferes  with 
the  clearness  of  striation  of  the  fibers. 
Fibers  of  this  latter  sort  are  usually  of  a 
deeper  color  than  those  in  which  the  sarco- 
plasm is  less  abundant,  and  the  two  varie- 
ties have  been  designated  as  the  red  (more 
abundant  sarcoplasm)  and  the  pale  fibers. 
Muscles  containing  chiefly  the  less  clearly 
striated  red  fibers,  for  example,  the  dia- 
phragm and  the  heart,  are  characterized 
physiologically  by  a  slower  rate  of  contrac- 
tion and  by  a  relatively  small  susceptibility 
to  fatigue.  The  so-called  red  and  pale  fibers 
may  occur  in  the  same  muscle.  The  sepa- 
rate fibrils,  like  the  entire  fiber,  show  two 
kinds  of  substance,  the  alternating  dim  and 
light  bands,  and  these  two  materials  are 
obviously  different  in  physical  structure  as 
seen  by  ordinary  light.  When  examined  by 
polarized  light,  this  difference  becomes  more  evident,  for  the  dim 
substance  possesses  the  property  of  double  refraction.  When  the 
muscle  fiber  is  placed  between  crossed  Nicol  prisms  the  dim  bands 


Fig.  3.— To  show  the 
appearance  of  the  dim 
(anisotrppic)  and  light 
(isotropic)  bands  at  rest 
and  in  contraction,  as  seen 
by  ordinary  and  by  polar- 
ized light.  The  figure  rep- 
resents a  muscle  fibril 
(beetle)  in  which  the  lower 
portion  has  been  fixed  in  a 
condition  of  contraction. 
On  the  left  the  relations  of 
the  dim  and  light  bands  are 
shown  as  they  appear  in 
ordinary  light,  in  the  re- 
laxed (upper  part) ,  and  the 
contracted  (lower  part) 
state.  On  the  right  the  re- 
lations of  the  bands  are 
shown  as  they  appear  when 
placed  between  crossed 
Nicol  prisms.  The  white 
spaces  represent  the  dim 
bands.  (Engelmann.) 


20         THE  PHYSIOLOGY  OF  .  MUSCLE  AND  NERVE. 

appear  bright,  while  the  light  bands  remain  dark,  as  is  shown 
in  Fig.  3.  From  this  standpoint  the  material  of  the  light 
bands  in  the  normal  fibrils  is  spoken  of  as  isotropous,  and  that  in 
the  dim  bands  as  anisotropous.  The  anisotropic  material  of  the 
dim  bands  consists  of  doubly  refracting  positive  uniaxial  particles, 
and  Engelmann  has  claimed  that  such  particles  may  be  discovered 
in  all  contractile  tissues.*  The  inference  made  by  him  is  that 
this  anisotropic  substance  is  the  contractile  material  in  the  pro- 
toplasm, the  machinery,  so  to  speak,  through  which  its  shortening 
is  accomplished.  Engelmann  supports  this  conclusion  by  the 
statement  that  during  contraction  the  size  of  the  dim  bands  in- 
creases at  the  expense  of  the  material  in  the  light  bands,  f  This 
theory  is  indicated  in  the  schema  given  in  Fig.  3.  The  relative 
changes  in  appearance  of  the  anisotropic  and  isotropic  bands 
during  the  phase  of  contraction,  which  are  shown  in  the  figure, 
may  be  explained  on  the  assumption  that  the  anisotropic  sub- 
stance absorbs  or  imbibes  water  from  the  isotropic  layer.  Engel- 
mann has  used  such  an  assumption  as  the  basis  for  a  theory  of  the 
shortening  of  the  muscle  (p.  71).  Unfortunately,  the  histological 
changes  indicated  in  Fig.  3  have  not  been  wholly  corroborated  by 
later  observers.  Hurthle  J  states  that  during  contraction  the 
anisotropic  band  may  shrink  to  less  than  one-half  its  width,  while 
the  isotropic  layer  shows  no  change.  He  finds  in  this  appearance 
a  confirmation  of  the  view  that  the  anisotropic  substance  consti- 
tutes the  active  contractile  material  of  the  muscle,  but  there  is 
no  evidence,  he  thinks,  to  support  the  assumption  that  the  change 
in  the  anisotropic  layer  is  due  to  imbibition  of  water  from  the 
isotropic  layer. 

The  Extensibility  and  Elasticity  of  Muscular  Tissue. — Muscular 
tissue,  when  acted  upon  by  a  weight,  extends  quite  readily,  and 
when  the  weight  is  removed,  it  regains  its  original  form  by  virtue 
of  its  elasticity.  In  our  bodies  the  muscles  stretched  from  bone 
to  bone  are,  in  fact,  in  a  state  of  elastic  tension.  If  a  muscle  is 
severed  by  an  incision  across  its  belly  the  ends  retract.  The 
extensibility  and  elasticity  of  the  muscles  add  to  the  effective- 
ness of  the  muscular-skeletal  machinery.  A  muscle  that  is  in  a 
state  of  elastic  tension  contracts  more  promptly  and  more  effec- 
tively for  a  given  stimulus  than  one  which  is  entirely  relaxed. 
Moreover,  in  our  joints  the  arrangement  of  antagonists — flexors 
and  extensors — is  such  that  the  contraction  of  one  moves  the 
bone  against  the  pull  of  the  extensible  and  elastic  antagonist. 

*  This  claim  has  been  denied,  see  Ellis,  "  American  Journal  of  Physiology," 
31,  370,  1913. 

t  Biedermann,  "Electro-physiology,"  vol.  i,  translated  by  Welby,  and 
Engelmann,  "Archiv  fur  die  gesammte  Physiologic,"  18,  1. 

J  Hurthle,  "Archiv  f.  d.  ges.  Physiologic,"  126,  1,  1909. 


THE    PHENOMENON    OF    CONTRACTION.  21 

It  would  seem  that  the  movements  of  the  skeleton  must  gain 
much  in  smoothness  and  delicacy  by  this  arrangement.  The 
physical  advantages  of  the  extensibility  and  elasticity  of  mus- 
cular tissue  are  evident  not  only  in  the  contractions  of  our  volun- 
tary muscles,  but,  as  we  shall  see,  in  a  striking  way  also  in  the 
circulation,  in  which  the  force  of  the  heart  beat  is  stored  and 
economically  distributed  by  the  elastic  tension  of  the  distended 
arteries.  The  extensibility  of  muscular  tissue  has  been  studied 
in  comparison  with  the  extensibility  of  dead  elastic  bodies.  With 


Fig.  4. — a,  Curve  of  extension  of  a  rubber  band,  to  show  the  equal  extensions  for  equal 
Increments  of  weight.  The  band  had  an  initial  load  of  17  gms.,  and  this  was  increased 
by  increments  of  3  gms.  in  each  of  the  nine  extensions,  the  final  load  being  44  gms.  The 
line  joining  the  ends  of  the  ordinates  is  a  straight  line.  6,  Curve  of  extension  of  a  frog's 
muscle  (gastrocnemius).  The  initial  load  and  the  increment  of  weight  were  the  same  as  with 
the  rubber.  The  curve  shows  a  decreasing  extension  for  equal  increments.  The  line  join- 
ing the  ends  of  the  ordinates  is  curved. 

regard  to  the  latter  it  is  known  that  the  strain  that  the  body 
undergoes  is  proportional,  within  the  limits  of  elasticity,  to  the 
stress  put  upon  it.  If,  for  instance,  weights  are  attached  to  a 
rubber  band  suspended  at  one  end,  the  amount  of  extension  of 
the  band  will  be  directly  proportional  to  the  weights  used.  If 
the  extensions  are  measured  the  relationship  may  be  represented 
as  shown  in  Fig.  4,  the  equal  increments  in  weight  being  indicated 
by  laying  off  equal  distances  on  the  abscissa,  and  the  resulting 
extensions  by  the  height  of  the  ordinates  dropped  from  each 
point.  If  the  ends  of  the  ordinates  are  joined,  the  result  is  a 
straight  line.  When  a  similar  experiment  is  made  with  a  living 
muscle  it  is  found  that  the  extension  is  not  proportional  to  the 
weight  used.  The  amount  of  extension  is  greatest  in  the  begin- 
ning and  decreases  proportionately  with  new  increments  of 
weight.  If  the  results  of  such  an  experiment  are  plotted,  as 
above,  representing  the  equal  increments  of  weight  by  equal 
distances  along  the  abscissa  and  the  resulting  extensions  by  ordi- 
nates dropped  from  these  points,  then  upon  joining  the  ends  of 


22 


THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE. 


the  ordinates  we  obtain  a  curve  concave  to  the  abscissa.  At 
first  the  muscle  shows  a  relatively  large  extension,  but  the  effect 
becomes  less  and  less  with  each  new  increment  of  weight,  the 
curve  at  the  end  approaching  slowly  to  a  horizontal.  If  the 
weight  is  increased  until  it  is  sufficient  to  overcome  the  elasticity 

of  the  muscle  the  curve  is  altered — it 
becomes  convex  to  the  abscissa,  or,  in 
other  words,  the  amount  of  extension 
increases  with  increasing  increments  of 
weight  up  to  the  point  of  rupture,  as 
shown  in  the  accompanying  curve* 
(Fig.  5).  Haycraftf  calls  attention  to 
the  fact  that  under  normal  conditions 
the  physiological  extension  of  the  frog's 
muscles  in  the  body  is  equal  to  that 
produced  by  a  weight  of  10  to  15  gms., 
and  that  when  the  excised  muscle  is 
extended  by  weights  below  this  limit  it 
follows  the  law  of  dead  elastic  bodies, 
giving  equal  extensions  for  equal  incre- 
ments of  weight.  It  is  only  after  pass- 
ing this  limit  that  the  law  stated  above 
holds  good.  It  should  be  added  also 
that  the  amount  of  deformation  ex- 
hibited by  a  muscle  or  other  living 
tissue  placed  under  a  stress  varies  with 
the  time  that  the  stress  is  allowed  to 
act.  The  muscle  is  composed  of  vis- 
cous material,  and  yields  slowly  to  the 
force  acting  upon  it.  In  experiments 
of  this  kind,  therefore,  the  weights 
should  be  allowed  to  act  for  equal 
intervals  of  time.  It  has  been  shown 
that  the  extensibility  of  a  muscle  is  greater  in  the  contracted 
than  in  the  resting  state. 

The  curve  of  extension  described  above  for  skeletal  muscle 
holds  also  for  so-called  plain  muscle.  This  latter  tissue  forms  a 
portion  of  the  walls  of  the  various  viscera,  the  stomach,  bladder, 
uterus,  blood-vessels,  etc.,  and  the  facts  shown  by  the  above  curve 
enter  frequently  into  the  explanation  of  the  physical  phenomena 
exhibited  by  the  viscera.  For  instance,  it  follows  from  this  curve 
that  the  force  of  the  heart  beat  will  cause  less  expansion  in  an 
artery  already  distended  by  a  high  blood-pressure  than  in  one  in 
which  the  blood-pressure  is  lower. 

*  See  Marey,  "  Du  mouvement  dans  les  fonctions  de  la  vie,"  1868,  p  284 
•j-Haycraft,  "Journal  of  Physiology,"  31,  392,  1904. 


Fig.  5. — Curve  given  by 
Marey  to  show  the  effect  upon 
the  extension  of  muscle  caused 
by  increasing  the  load  regularly 
to  the  point  of  rupture:  From 
o  to  a  the  extension  of  the 
muscle  decreases  as  the  weight 
increases,  giving  a  curve  concave 
to  the  abscissa;  at  a  the  limit 
of  elasticity  is  passed  and  the 
muscle  lengthens  by  increasing 
extensions  for  equal  increments; 
at  x  rupture  (750  gms.  for  frog's 
gastrocnemius). 


THE    PHENOMENON    OF    CONTRACTION.  23 

The  Irritability  and  Contractility  of  Muscle. — Under  normal 
conditions  in  the  body  a  muscle  is  made  to  contract  by  a  stimulus 
received  from  the  central  nervous  system  through  its  motor  nerve. 
If  the  latter  is  severed  the  muscle  is  paralyzed.  We  owe  to  Haller, 
the  great  physiologist  of  the  eighteenth  century,  the  proof  that 
a  muscle  thus  isolated  can  still  be  made  to  contract  by  an  artificial 
stimulus — e.  g.,  an  electrical  shock — applied  directly  to  it.  This 
significant  discovery  removed  from  physiology  the  old  and  harmful 
idea  of  animal  spirits,  which  were  supposed  to  be  generated  in  the 
central  nervous  system  and  to  cause  the  swelling  of  a  muscle  during 
contraction  by  flowing  to  it  along  the  connecting  nerve.  But  to 
remove  a  muscle  from  the  body  and  make  it  contract  by  an  artificial 
stimulus  does  not  prove  that  the  muscle  substance  itself  is  capable 
of  being  acted  upon  by  the  stimulus,  since  in  such  an  experiment 
the  endings  of  the  nerve  in  the  muscle  are  still  intact,  and  it  may 
be  that  the  stimulus  acts  only  on  them  and  thus  affects  the  mus- 
cle indirectly.  In  a  number  of  ways,  however,  physiologists  have 
found  that  the  muscle  substance  can  be  made  to  contract  by  a 
stimulus  applied  directly  to  it,  and  therefore  exhibits  what  is 
known  as  independent  irritability.  The  term  irritability,  according 
to  modern  usage,  means  that  a  tissue  can  be  made  to  exhibit  its 
peculiar  form  of  functional  activity  when  stimulated, — e.  g.,  a 
muscle  cell  will  contract,  a  gland  cell  will  secrete,  etc., — and  inde- 
pendent irritability  in  the  case  under  consideration  means  simply 
that  the  muscle  gives  its  reaction  of  contraction  when  artificial 
stimuli  are  applied  directly  to  its  substance.  This  conception 
of  irritability  was  first  introduced  by  Francis  Glisson  (1597-1677), 
a  celebrated  English  physician.*  Subsequent  writers  frequently 
used  the  term  as  synonymous  with  contractility  and  as  applicable 
only  to  the  muscle.  But  it  is  now  used  for  all  living  tissues  in 
the  sense  here  indicated.  A  simple  proof  of  the  independent 
irritability  of  a  striated  muscle  is  obtained  by  cutting  the  motor 
nerve  going  to  it  and  stimulating  the  muscle  after  several  days. 
We  know  now  that  in  the  course  of  several  days  the  severed  nerve 
fibers  degenerate  completely  down  to  their  terminations  in  the 
muscle  fibers,  and  the  muscle,  thus  freed  from  its  nerve  fibers  by 
the  process  of  degeneration,  can  still  be  made  to  contract  by  an 
artificial  stimulus.  The  classical  proof  of  the  independent  irri- 
tability of  muscle  fibers  was  given  by  Claude  Bernard,  the  great 
French  physiologist  of  the  nineteenth  century.  He  made  use 
of  the  so-called  arrow  poison  of  the  South  American  Indians. 
This  substance  or  mixture  of  substances  is  known  generally  under 
the  name  curare;  it  is  prepared  from  the  juices  of  several  plants 
(strychnos)  (Thorpe) .  The  poisonous  part  of  the  material  is  soluble 
*  See  Foster's  "History  of  Physiology,"  p.  287. 


24         THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE. 

in  water,  and  Bernard  showed  that  when  such  an  extract  is  injected 
into  the  blood  or  hypodermically  it  paralyzes  the  motor  nerves 
at  their  peripheral  end,  so  that  direct  stimulation  of  these  nerves 
is  ineffective.  Direct  stimulation  of  the  muscle  substance,  on  the 
contrary,  causes  a  contraction.*  We  are  justified,  therefore,  in 
saying  that  skeletal  muscle  possesses  the  properties  of  independ- 
ent contractility  (Haller)  and  independent  irritability  (Ber- 
nard). By  the  former  term  we  mean  that  the  shortening  of  the 
muscle  is  due  to  active  processes  developed  in  its  own  tissue, 
by  the  latter  we  mean  that  the  muscular  tissue  may  be  made 
to  enter  into  contraction  by  artificial  stimuli  applied  directly 
to  its  own  substance.  This  latter  property  cannot  be  said  to 
hold  for  all  the  tissues.  Whether  a  nerve  cell  or  a  gland  cell  may  be 
made  to  enter  into  its  specific  form  of  activity  by  the  direct  appli- 
cation of  an  artificial  stimulus  is  still  a  debatable  question. 

Artificial  Stimuli. — If  we  designate  the  stimulus  that  the 
muscle  receives  normally  from  its  nerve  as  its  normal  stimulus, 
all  other  forms  of  energy  which  may  be  used  to  start  its  contraction 
may  be  grouped  under  the  designation  artificial  stimuli.  Experi- 
ments have  shown  that  a  contraction  may  be  aroused  by  mechani- 


Fig.  6. — The  induction  coil  as  used  for  physiological  purposes  (du  Bois-Reymond 
pattern):  A,  The  primary  coil;  B,  the  secondary  coil;  P',  binding  posts  to  which  are  at- 
tached the  wires  from  the  battery,  they  connect  with  the  ends  of  coil  A;  P",  binding  posts 
connecting  with  ends  of  coil  B,  through  which  the  induction  current  is  led  off;  S,  the  slide, 
with  scale,  in  which  coil  B  is  moved  to  alter  its  distance  from  A. 

caf  stimuli, — for  instance,  by  a  sharp  blow  applied  to  the  muscle;  by 
thermal  stimuli, — that  is,  by  a  sudden  change  in  temperature;  by 
chemical  stimuli, — for  example,  by  the  action  of  concentrated  solu- 
tions of  salts,  and  finally  by  electrical  stimulL>  In  practice,  how- 
ever, only  the  last  form  of  stimulus  is  found  to  fee  convenient.  The 
mechanical  and  thermal  stimuli  cannot  be  well  applied  without  at 
the  same  time  injuring  the  muscle  substance,  and  the  same  is  prob- 
ably true  of  chemical  stimuli,  which  possess  the  disadvantage,  more- 
over, of  not  exciting  simultaneously  the  different  fibers  of  which 
the  muscle  is  composed.  Electrical  stimuli,  on  the  contrary,  are 

*  "Lemons  sur  les  effets  des  substances  toxiques  et  m^dicamenteuses," 
1857,  pp.  238  et  seq. 


THE    PHENOMENON    OF    CONTRACTION.  25 

applied  easily,  are  readily  controlled  as  regards  their  intensity,  and 
affect  all  the  fibers  simultaneously,  thus  giving  a  co-ordinated 
contraction  of  the  entire  bundle,  as  is  the  case  with  the  normal 
stimulus.  For  electrical  stimulation  we  may  use  the  galvanic 
current  taken  directly  from  the  battery,  or  the  induced  or  so-called 
faradic  current  obtained  from  an  induction  coil.  Under  most 
conditions  the  latter  is  more  convenient,  since  it  gives  brief  shocks, 
the  strength  and  number  of  which  can  be  controlled  readily.  The 
form  in  which  this  instrument  is  used  in  experimental  work  in 
physiology  we  owe  to  du  Bois-Reymond;  hence  it  is  frequently 
known  as  the  du  Bois-Reymond  induction  coil.  Experimental 
physiology  owes  a  great  deal  to  this  simple  and  serviceable  in- 


Fig.  7. — Schema  of  induction  apparatus. — (Lombard.)  b  represents  the  galvanic 
battery  connected  by  wires  to  the  primary  coil,  A.  On  the  course  of  one  of  these  wires 
is  a  key  (k)  to  make  and  break  the  current.  B  shows  the  principle  of  the  secondary 
coil,  and  the  connection  of  its  two  ends  with  the  nerve  of  a  nerve-muscle  preparation. 
When  the  battery  current  is  closed  or  made  in  A,  a  brief  current  of  high  intensity  is 
induced  in  B.  This  is  known  as  the  making  or  closing  shock.  When  the  battery  current 
is  broken  in  A,  a  second  brief  induction  current  is  aroused  in  B.  This  is  known  as  the 
breaking  or  opening  shock. 

strument.     A  figure  and  brief  description  of  the  apparatus  are 
appended  (Figs.  6  and  7). 

Simple  Contraction  of  Muscle. — Experiments  may  be  made 
upon  the  muscles  of  various  animals,  but  ordinarily  in  physiolog- 
ical laboratories  one  of  the  muscles  (gastrocnemius)  of  the  hind 
leg  of  the  frog  is  employed.  If  such  a  muscle  is  isolated  and 
connected  with  the  terminals  from  an  induction  coil  it  may  be 
stimulated  by  a  single  shock  or  by  a  series  of  rapidly  repeated 
shocks.  The  contraction  that  results  from  a  single  stimulus 
is  designated  as  a  simple  contraction.  In  the  frog's  muscle  it  is 
very  brief,  lasting  for  0.1  second  or  less;  but  in  this,  as  in  other 
respects,  cross-striated  muscular  tissue  varies  in  different 
animals,*  as  is  shown  by  the  accompanying  table,  which  gives  a 
general  idea  of  the  range  of  rapidity  of  contraction : 

*  Cash,  "Archiv  f.  Anat.  u.  Physiol.,"  1880,  suppl.  volume,  p.  147. 


26          THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE. 

DURATION  OF  A  SIMPLE  MUSCULAR  CONTRACTION. 

Insect 0.003  sec. 

Rabbit  (Marey) 0.070     " 

Frog 0.100     " 

Terrapin 1.000 

The  series  may  be  continued  by  the  figures  obtained  from  the 
plain  muscle,  thus: 

The  involuntary  muscle  (mammal) 10.00 

Foot  muscle  of  slug*  (Ariolimax) 20.00 

The  duration  of  the  simple  contraction  varies  considerably 
in  the  muscles  of  different  parts  of  the  same  animal.  Thus, 
according  to  Cash,  the  hyoglossal  muscle  in  the  frog  requires 
0.205  to  0.3  second,  while  the  gastrocnemius  takes  0.12  second; 
in  the  tortoise  the  pectoralis  major  requires  1.8  seconds,  the 
omohyoid  only  0.55  second;  in  the  rabbit  the  soleus  (a  red 
muscle)  requires  1  second,  the  gastrocnemius  (a  pale  muscle) 
0.25  second.  On  examining  into  these  differences  it  may  be 
shown  that  the  variations  bear  a  relation  to  the  special  functions 
of  the  muscles.  Where  rapid  movements  are  requisite  or  advan- 
tageous the  muscle  shows  the  property  of  quick  contraction  and 
relaxation,  while  in  other  places,  in  which  maintenance  of  con- 
traction is  the  more  important  feature,  the  properties  of  the 
muscle  have  been  developed  so  as  to  adapt  them  to  this  kind  of 
contraction.  The  skeletal  and  the  plain  muscles  exhibit  the 
extreme  examples  in  this  form  of  adaptation. 

The  Curve  of  Contraction. — When  a  contracting  muscle  is 
attached  to  a  lever  this  lever  may  be  made  to  write  upon  a  smoked 
surface  and  thus  record  the  movement,  more  or  less  magnified 
according  to  the  leverage  chosen.  If  the  recording  surface  is  sta- 
tionary the  record  obtained  is  a  straight  line  and  indicates  only  the 
extent  of  the  shortening.  If,  however,  the  recording  surface  is  in 
movement  during  the  contraction  the  record  will  be  in  the  form  of  a 
curve,  which,  making  use  of  the  system  of  right-angled  co-ordinates, 
will  indicate  not  only  the  full  extent  of  the  shortening,  but  also 
the  amount  of  shortening  or  subsequent  relaxation  at  any  moment 
during  the  entire  period.  To  obtain  such  records  from  the  rapidly 
contracting  frog's  muscle  it  is  evident  that  the  recording  surface 
must  move  with  considerable  rapidity  and  with  a  uniform  velocity. 
A  curve  of  this  kind  is  represented  in  Fig.  81  C  represents 
the  axis  of  abscissas  and  gives  the  factor  of  time.  A  vertical 
ordinate  erected  at  any  point  on  C  gives  the  extent  of  shortening 
at  that  moment.  Below  the  curve  of  the  muscle  is  the  record 
of  the  vibrations  of  a  tuning  fork  giving  100  double  vibrations 
per  second;  that  is,  the  distance  from  crest  to  crest  represents  an 
*  Carlson,  "American  Journal  of  Physiology,"  10,  418,  1904. 


THE    PHENOMENON    OF    CONTRACTION.  27 

interval  of  rhr  of  a  second.  Three  principal  facts  are  brought  out 
by  an  analysis  of  the  curve:  I.  The  latent  period.  By  this  is 
meant  that  the  muscle  does  not  begin  to  shorten  until  a  certain 
time  after  the  stimulus  is  applied.  On  the  curve  the  stimulus 


Fig.  8. — Curve  of  simple  muscular  contraction. 

enters  the  muscle  at  S,  and  the  distance  between  this  point  and  the 
beginning  of  the  rise  of  the  curve,  interpreted  in  time,  is  the  latent 
period.  II.  The  phase  of  shortening,  which  has  a  definite  course 
and  at  its  end  immediately  passes  into  III.,  the  phase  of  relaxation. 

The  Latent  Period. — In  the  contraction  of  the  isolated  frog's 
muscles  as  usually  recorded  the  latent  period  amounts  to  0.01  sec., 
but  it  is  generally  assumed  that  this  period  is  exaggerated  by  the 
method  of  recording  used,  since  the  elasticity  of  the  muscle  itself 
prevents  the  immediate  registration  of  the  movement.  By  improve- 
ments in  methods  of  technique  the  latent  period  for  a  fresh  muscle 
may  be  reduced  to  as  little  as  0.005  or  even  0.004  sec.  Under  the 
conditions  in  the  body,  however,  the  muscle  contracts  against  a 
load,  as  when  lifting  a  lever;  hence,  we  may  assume  that  normally 
there  is  a  lost  time  of  at  least  0.01  sec.  after  the  stimulus  enters  the 
muscle.  In  addition  to  the  latent  period  due  to  the  elasticity 
of  the  muscle  it  is  certain  that  a  brief  amount  of  time  actually 
elapses  after  the  stimulus  enters  the  muscle  before  the  act  of 
shortening  begins;  some  time  is  taken  up  in  the  antecedent  physical 
and  chemical  changes  caused  by  the  stimulus,  and  the  effect  of 
these  changes  in  putting  the  mechanism  of  contraction  into  play 
(see  below  on  the  Theory  of  Muscle  Contractions).  The  latent 
period  varies  greatly  in  muscles  of  different  kinds,  and  in  the  same 
muscle  varies  with  its  conditions  as  regards  temperature,  fatigue, 
load  to  be  raised,  etc. 

The  Phases  of  Shortening  and  of  Relaxation. — In  the  normal 
frog's  muscle  the  phase  of  shortening  for  a  simple  contraction  occu- 
pies about  0.04  second,  while  the  relaxation  may  be  a  trifle  longer, 
0.05  sec.  In  muscles  whose  duration  of  contraction  differs  from 


28          THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE. 

that  of  the  frog  the  time  values  for  the  shortening  and  the  relaxation 
exhibit  corresponding  differences.  As  we  have  seen,  the  appearance 
of  the  muscle  fiber  when  viewed  by  polarized  light  indicates  that 
during  the  phase  of  shortening  the  most  marked  physical  change 
occurs  in  the  anisotropic  band.  Whatever  may  be  the  nature 
of  this  change,  it  is  evidently  a  reversible  one.  After  reaching 
its  maximum  it  proceeds  in  the  opposite  direction,  the  particles 
return  to  their  original  position,  and  a  relaxation  occurs.  Many 
conditions,  some  of  which  will  be  described  below,  alter  the  time 
necessary  for  these  processes,  that  is,  the  duration  of  the  simple 
contraction.  It  is  noteworthy  that  it  is  the  phase  of  relaxation 
which  may  be  most  easily  prolonged  or  shortened  by  varying 
conditions. 

Isotonic  and  Isometric  Contractions. — In  the  method  of  recording  the 
shortening  of  the  muscle  that  is  described  above  the  muscle  is  supposed  to  con- 
tract against  a  constant  load  which  it  can  lift.  Such  a  contraction  is  spoken 
of  as  an  isotonic  contraction.  If  the  muscle  is  allowed  to  contract  against 
a  tension  too  great  for  it  to  overcome — a  stiff  spring,  for  instance — it  is  prac- 
tically prevented  from  shortening,  and  a  contraction  of  this  kind,  in  which 
the  length  of  the  muscle  remains  unchanged,  is  spoken  of  as  an  isometric 


Fig.  9. — Effect  of  varying  the  strength  of  stimulus.  The  figure  shows  the  effect  upon 
the  gastrocnemius  muscle  of  a  frog  of  gradually  increasing  the  stimulus  (breaking  induction 
shock)  until  maximum  contractions  were  obtained.  The  stimuli  were  then  decreased  in 
strength  and  the  contractions  fell  off  through  a  series  of  gradually  decreasing  submaximal 
contractions.  The  series  up  and  down  is  not  absolutely  regular  owing  to  the  difficulty  of 
obtaining  a  regular  increase  or  decrease  in  the  stimulus.  (The  prolongations  of  the 
curves  below  the  base  line  are  due  to  the  elastic  extension  of  the  muscle  by  the  weight  dur- 
ing relaxation.) 

contraction.  A  curve  of  such  a  contraction  may  be  obtained  by  magnifying 
greatly,  by  means  of  levers,  the  slight  change  in  the  stiff  spring  against  which 
the  muscle  is  contracting.  Such  a  curve  gives  a  picture  of  the  liberation  of 
energy  within  the  muscle  during  contraction. 

The  usual  oval  form  of  dynamometer  employed  to  record  the  grip  of  the 
flexors  of  the  fingers  gives  an  isometric  record  of  the  energy  of  contraction 
of  these  muscles. 


THE    PHENOMENON    OF    CONTRACTION.  29 

Effect  of  Strength  of  Stimulus  upon  the  Simple  Contraction. 

— The  strength  of  electrical  stimuli  can  be  varied  conveniently  and 
with  great  accuracy.  When  the  stimulus  is  of  such  a  strength  as 
to  produce  a  just  visible  contraction  it  is  spoken  of  as  a  minimal 
stimulus  and  the  resulting  contraction  as  a  minimal  contraction. 
Stimuli  of  less  strength  than  the  minimal  are  designated  as  sub- 
minimal.  If  one  increases  gradually  the  intensity  of  the  electrical 
current  used  as  a  stimulus  without  altering  its  duration,  beginning 
with  a  stimulus  sufficient  to  cause  a  minimal  contraction,  the  result- 
ing contractions  increase  proportionally  up  to  a  certain  maximum 
beyond  which  further  increase  of  stimulus,  other  conditions  remain- 
ing the  same,  causes  no  greater  extent  of  shortening.  Contrac- 
tions between  the  minimal  and  the  maximal  are  designated  as 
submaximal.  (See  Fig.  9.) 

This  phenomenon  of  submaximal  contractions  was  formerly 
interpreted  as  a  graded  response  to  graded  stimuli,  and  it  was  as- 
sumed that  a  similar  result  would  be  obtained  from  a  single  fiber  if 
it  were  possible  to  experiment  with  it.  A  weak  stimulus  would 
give  a  weak  contraction  and  a  stronger  stimulus  a  stronger  con- 
traction, up  to  the  maximum.  '  Some  years  ago  Lucas*  found  that 
when  a  small  slip  of  muscle  containing  a  few  fibers  is  stimulated  it 
does  not  give  a  smoothly  graded  increase  in  contraction  as  the 
stimulus  is  increased,  but,  on  the  contrary,  exhibits  abrupt  jumps 
from  one  level  to  another.  He  suggested,  therefore,  that  the  indi- 
vidual fibers  follow  the  "all  or  none  law"  with  which  we  are 
familiar  in  the  case  of  heart  muscle;  that  is  to  say,  a  fiber  when 
stimulated  gives  a  maximal  contraction  or  none  at  all.  The  sub- 
maximal  contractions  observed  in  the  whole  muscle  are  simply  the 
expression  of  the  activity  of  a  part  of  the  fibers.  The  theoretical 
minimal  contraction  would  be  the  contraction  of  a  single  fiber  in 
the  group  composing  a  muscle,  while  the  theoretical  maximal  con- 
traction would  be  the  combined  effect  of  the  contraction  of  all  the 
fibers.  This  point  of  view  seems  to  have  found  favor  with  most  of 
the  workers  who  have  investigated  the  matter,  f 

Effect  of  Temperature  upon  the  Simple  Contraction. — Varia- 
tions in  temperature  affect  both  the  extent  and  the  duration  of  the 
contraction.  The  relationship  is,  however,  not  a  simple  one  in  the 
case  of  the  frog's  muscle  upon  which  it  has  been  studied  most  fre- 
quently. If  we  pay  attention  to  the  extent  of  the  contraction  alone 
it  will  be  found  that  at  a  certain  temperature,  0°  C.  or  slightly  be- 
low, the  muscle  loses  its  irritability  entirely.  As  its  temperature  is 
raised  a  given  stimulus,  chosen  of  such  a  strength  as  to  be  maximal 

*  Lucas,  "Journal  of  Physiology,"  1905,  33,  125,  and  1909,  38,  113. 
f  Consult  Pratt,  "American  Journal  of  Physiology,"  1917,  43, 159,  and  44, 
517,  and  Eisenberger,  ibid.,  1917,  45,  44. 


30 


THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE. 


for  the  muscle  at  room  temperatures,  causes  greater  and  greater 
contractions  up  to  a  certain  maximum,  which  is  reached  at  about 
5°  to  9°  C.  As  the  temperature  rises  beyond  this  point  the  con- 


Fig.  10. — Curve  showing  the  effeet  of  temperature.  The  temperatures  at  which  the 
contractions  were  obtained  are  indicated  on  the  figure.  In  this  experiment  a  large  resis- 
tance was  introduced  into  the  secondary  circuit  so  that  changes  va  the  resistance  of  the 
muscle  itself  due  to  heatiog  could  not  affect  the  strength  of  the  stimulus. 


Fig.  11. — Curve  to  show  the  effect  of  a 
rioe  of  temperature  from  0°  C.  to  38°  C.  upon 
the  height  of  contraction  of  frog's  muscle. 
The  first  maximum  at  9°  C.  the  second  at 
28°  C.  Beyond  38°  C.  the  muscle  lost  its 
irritability  and  went  into  rigor  mortis. 


Fig.  12. — Curve  to  show  the  effect 
of  a  rise  of  temperature  from  5°  C.  to 
39  C.  upon  the  duration  of  contraction 
of  frog's  muscle.  The  relative  dura- 
tions at  the  different  temperatures  are 
represented  by  the  height  of  the  cor- 
responding ordinates. 


THE    PHENOMENON    OF    CONTRACTION.  31 

tractions  decrease  somewhat  to  a  minimum  that  is  reached  at  about 
15°  to  18°  C.  Beyond  this  the  contractions  again  increase  in 
extent  to  a  second  maximum  at  about  26°  to  30°  C.,  this  maxi- 
mum being  in  some  cases  greater,  and  in  others  less  than  the  first 
maximum.  Beyond  the  second  maximum  the  contractions  again 
decrease  rather  rapidly  as  the  temperature  rises  until  at  a  certain 
temperature,  37°  C.,  irritability  is  entirely  lost  (Fig.  10).  If  the  tem- 
perature is  raised  somewhat  beyond  this  latter  point  heat  rigor  makes 
its  appearance,  and  the  muscle  may  be  considered  as  dead.  The  re- 
lationship between  temperature  and  extent  of  contraction,  therefore, 
may  be  expressed  by  a  curve  such  as  is  represented  in  Fig.  11,  in 
which  there  are  two  maxinwand  two  points  at  which  irritability  is 
lost.  The  second  maximum  indicates  a  fact  of  general  physiological  in- 
terest,— namely,  that  in  all  of  the  tissues  of  the  body  there  is  a  certain 
high  temperature  at  which  optimum  activity  is  exhibited,  and  if  the 
temperature  is  raised  beyond  this  point  functional  activity  becomes 
more  and  more  depressed.  The  point  of  optimum  effect  is  not  iden- 
tical for  the  different  tissues  of  the  same  animal,  much  less  so  for 
those  of  different  animals,  but  the  fact  may  be  emphasized  that  in 
no  case  do  protoplasmic  tissues  withstand  a  very  high  temperature. 
Functional  activity  is  lost  usually  at  45°  C.  or  below.  The  duration 
of  the  contraction  shows  usually  in  frogs'  muscles  a  simple  relation- 
ship to  the  changes  of  temperature.  At  low  temperatures,  4  or  5°  C., 
the  contractions  are  enormously  prolonged,  particularly  in  the  phase 
of  relaxation  ;  but  as  the  temperature  is  raised  the  duration  of  the 
contractions  diminishes,  at  first  rapidly,  then  more  slowly,  to  a 
certain  point — about  18°  to  20°  C.,  beyond  which  it  remains  more  or 
less  constant  hi  spite  of  the  changes  in  extent  of  shortening.  The 
relationship  between  duration  of  contraction  and  temperature  may 
therefore  be  expressed  by  such  a  curve  as  is  shown  in  Fig.  12,  in 
which  the  heights  of  the  ordinates  represent  the  relative  durations 
of  the  contractions.  Muscles  from  different  frogs  show  considerable 
minor  variations  in  their  reactions  to  changes  in  temperature,  and 
we  may  suppose  that  these  variations  depend  upon  differences  in 
nutritive  condition.  In  this,  as  in  many  other  respects,  the  reac- 
tions obtained  from  so-called  winter  frogs  after  they  have  prepared 
for  hibernation  are  more  regular  and  typical  than  those  obtained 
ID  the  spring  or  summer. 

Effect  of  Veratrin. — The  alkaloid  veratrin  exhibits  a  peculiar 
and  interesting  effect  upon  the  contraction  of  muscle.  A  muscle 
taken  from  a  veratrinized  animal  and  stimulated  in  the  usual 
way  by  a  single  stimulus  gives  a  contraction  such  as  is  exhibited 
in  the  accompanying  curve  (Fig.  13).  Two  peculiarities  are  shown 
by  the  curve:  (1)  The  phase  of  shortening  is  not  altered,  but  the 
phase  of  relaxation  is  greatly  prolonged.  (2)  The  curve  shows 


32  THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 

two  summits, — that  is,  after  the  first  shortening  there  is  a  brief 
relaxation  followed  by  a  second,  slower  contraction.  The  cause 
of  this  second  shortening  is  not  known.  Biedemann  has  sug- 
gested that  it  is  due  to  the  presence  in  the  muscle  of  the  two  kinds 
of  fibers — red  and  pale — which  were  spoken  of  on  p.  19,  and  that 


Fig.  13. — Curve  showing  the  effect  of  veratrin. 

the  veratrin  dissociates  their  action,  but  this  explanation,  ac- 
cording to  Carvallo  and  Weiss,*  is  disproved  by  the  fact  that 
muscles  composed  entirely  of  white  or  red  fibers  show  a  similar 
result  from  the  action  of  veratrin.  It  would  seem  more  probable1, 
therefore,  that  two  different  contraction  processes  are  initiated  by 
the  stimulus,  one  much  more  rapid  than  the  other.  Many  other' 
facts  in  physiology  speak  for  this  general  view  that  a  muscle  may, 
according  to  conditions,  give  either  a  quick  contraction  (twitch) 
or  a  more  slowly  developing  contraction,  with  a  prolonged  phase  of 
relaxation  (tone  contraction).  This  latter  feature  constitutes  the 
characteristic  peculiarity  of  the  curve  of  a  veratrin  contraction. 
A  somewhat  similar  effect  is  produced  by  the  action  of  glycerin, 
nicotine,  etc.  We  have  in  such  substances  reagents  that  affect 
one  phase  of  the  contraction  process  without  materially  influenc- 
ing the  other.  As  regards  the  veratrin  effect,  it  becomes  less  and 
less  marked  if  the  muscle  is  made  to  give  repeated  contractions, 
but  reappears  after  a  suitable  period  of  rest.  The  peculiar  action 
of  the  veratrin  is,  therefore,  antagonized  seemingly  by  the  chemkial 
products  formed  during  contraction. 

Contracture. — The  jgrolqnged  relaxation  that  is  so  character- 
istic of  the  veratrimzed  muscles  may  be  observed  in  frog's  muscle 
under  other  circumstances,  and  is  described  usually  as  a  con- 
dition of  contracture.  By  Contracture  we  mean  a  state  of  main- 
tained contraction  or,  looking  at  it  from  the  other  point  of  view, 
ii  state  of  retarded  relaxation. 

This  condition  is  often  exhibited  in  a  most  interesting  way  when  a  muscle 
is  repeatedly  stimulated.  In  some  cases  it  develops  at  the  beginning  of  a 
series  of  contractions,  as  is  represented  in  Fig.  14,  which  pictures  the  phenome- 
non as  it  was  first  described.!  In  other  cases  it  appears  later  on  in  the  curve, 

*  "Journal  de  la  physiol.  et  de  la  path,  generale,"  1899. 
fTiegel,  "Pfliiger's  Archiv  fur  die  gesammte  Physiologic,"  etc.,  13,  71, 
1876. 


THE    PHENOMENON    OF    CONTRACTION. 


33 


preceding  or  following  the  development  of  the  state  of  fatigue.  Whenever 
it  occurs  the  effect  is  to  hold  the  muscle  in  a  state  of  maintained  contraction  or 
tone,  on  which  is  superposed  the  series  of  quick  contractions  and  relaxations 
due  to  the  separate  stimuli.  When  the  condition  develops  early  in  the  func- 


tional activity  of  the  muscle  (Fig.  14)  further  activity  usually  causes  it  to  dis- 
appear, and  the  condition  of  the  muscle  as  a  mechanism  for  prompt  shortening 
and  relaxation  is  improved.  We  have  in  this  fact  apparently  an  indication 
of  one  way  in  which  the  " warming  up"  exercise  before  athletic  contests  may  be 
3 


34         THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE. 

of  value.  When  the  contraction  appears  late  in  the  series  of  contractions 
it  is  usually  permanent,  that  is  to  say,  it  wears  off  only  as  the  muscle  relaxes 
slowly  from  fatigue.  Toward  the  end  of  such  a  series  the  muscle  is  often 
practically  in  a  state  of  continuous  contraction,  a  condition  which  would 
nullify  its  ordinary  use  in  locomotion.  It  seems  possible  that  certain  con- 
ditions of  tonic  spasm  or  cramps  which  occur  during  life  may  involve  this 
process,  for  example,  the  temporary  cramp  that  sometimes  attacks  a  player 


Fig.  15. — Effect  of  repeated  stimulation;  complete  curve,  showing  late  contracture. 
The  muscle  was  stimulated  by  induction  shocks  at  the  rate  of  50  per  minute.  The  separate 
contractions  are  so  close  together  that  they  can  not  be  distinguished. 


Fig.  16. — Effect  of  repeated  stimulation,  curve  showing  no  contracture  or  very  little. 
The  muscle  was  stimulated  by  induction  shocks  at  the  rate  of  50  per  minute.  A  very 
slight  contracture  is  shown  in  the  beginning,  but  subsequently  the  contractions  show 
«.nly  a  diminished  extent,  the  rate  of  relaxation  remaining  apparently  unchanged. 

in  athletic  games,  or  the  curious  spasmodic  condition  known  as  intermittent 
claudication,  in  which  the  muscles  on  exercise  are  thrown  into  a  state  of 
tonic  contraction.  From  the  physiological  standpoint  the  phenomenon  of 
contracture  when  compared  with  that  of  the  simple  contraction  indicates  the 
possibility  that  two  different  contraction  processes  may  take  place  in  muscle, 
one  involving  the  state  of  tone  and,  therefore,  the  length  and  hardness  of 
the  muscle,  the  other  controlling  the  movements  proper.  This  suggestion 


THE    PHENOMENON    OF    CONTRACTION.  35 

has  been  made  by  a  number  of  authors*  on  various  grounds.  It  has  been 
suggested  by  some  that  there  are  two  different  contractile  substances  in  mus- 
cle, one  giving  the  usual  quick  contraction,  known  as  a  "twitch,"  the  other 
the  slower  contraction,  which  exhibits  itself  as  tone  or  contracture.f 

The  Effect  of  Rapidly  Repeated  Contractions. — When  a  mus- 
cle is  stimulated  repeatedly  by  stimuli  of  equal  strength  that 
fall  into  the  muscle  at  equal  intervals  the  contractions  show  cer- 
tain features  that,  in  a  general  way,  are  constant,  although  the  pre- 
cise degree  in  which  they  are  exhibited  varies  curiously  in  different 
animals.  Such  curves  are  exhibited  in  Figs.  14,  15,  and  16,  and 
the  features  worthy  of  note  may  be  specified  briefly  as  follows: 

1.  The  Introductory  Contractions. — The  first  three  or  four  con- 
tractions decrease  slightly  in  extent,  showing  that  the  muscle  at 
first  loses  a  little  in  irritability  on  account  of  previous  contractions. 
This  phenomenon  is  frequently  absent. 

2.  The  Staircase  or  "  Treppe."— After  the  first  slight    fall  in 
height  has  passed  off  the  contractions  increase  in  extent  with  great 
regularity  and  often  for  a  surprisingly  large  number  of  contractions. 
This  gradual  increase  in  extent  of  shortening,  with  a  constant 
stimulus,  was  first  noticed  by  Bowditch  upon  the  heart  muscle, 
and    was    by    him    named    the    phenomenon    of    "treppe,"   the 
German  word  for  staircase.     It  indicates  that  the  effect  of  activity 
is  in  the  beginning  beneficial  to  the  muscle  in  that  its  irritability 
steadily  increases,  and  the  fact  that  the  same  result  has  been  ob- 
tained from  heart  muscle,  plain  muscle,  and  nerve  fibers  indicates 
that  it  may  be  a  general  physiological  law  that  functional  activity 
leads  at  first  to  a  heightened  irritability^.     According  to  Lee,J 
the  "treppe"  in  muscle  is  due  to  an  initial  increase  of  irritability 
set  up  by  the  chemical  products  formed  during  contraction. 

3.  Contracture. — This  phenomenon  of  maintained  contraction 
has  b^en  described  above.     In  frogs'  muscles  stimulated  repeat- 
edly it  makes  its  appearance,  as  a  rule,  sooner  or  later  in  the 
series  of  contractions;  but  there  is  a  curious  amount  of  variation 
in  the  muscles  of  different  individuals  in  this  respect. 

4.  Fatigw. — After  the  period  of  the  "  treppe  "  has  passed,  the 
contractions  diminish  steadily  in  height,  until  at  last  the  muscle 
fails  entirely  to  respond  to  the  stimulus.     This  progressive  loss  of 
irritability  in  the  muscle  caused  by  repeated  activity  is  designated 
as  fatigue.     It  will  be  considered  more  in  detail  under  the  head  of 
Compound    Muscular    Contractions    and   in    Chapter    II.     The 
curve  obtained  in  an  experiment  of  this  kind  illustrates  in  a 

*  See  especially  Uexkull,  "Zentralblatt  f.  Physiologic,"  1908,  22,  33;  also 
Guenther,  ''American  Journal  of  Physiology,"  1905,  14,  73. 

t  loteyko,  "Travaux  du  labaratoire  de  Physiologie,"  Institut  Solvay,  1902, 
5,  229. 

J  See  "American  Journal  of  Physiology,"  1907,  18,  267. 


36  THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 

striking  way  one  of  the  general  characteristics  of  living  matter, 
namely,  that  every  effective  stimulus  applied  to  it  leaves  a  record, 
so  to  speak.  The  muscle  in  this  case  is  in  a  changed  condition 
.after  each  stimulus,  as  is  indicated  by  the  difference  in  its  re- 
sponse to  the  succeeding  stimulus.  While  it  cannot  be  said  that 
a  similar  effect  has  been  shown  in  all  tissues,  still  the  evidence  in 
general  points  that  way,  and  some  of  the  complicated  phenomena 
exhibited  by  living  matter,  such  as  memory,  habits,  immunity, 
etc.,  are  referable  in  the  long  run  to  this  underlying  peculiarity. 

Lee  has  discovered  the  interesting  fact  that  while  in  frog's  muscle,  as  a 
rule,  fatigue  is  accompanied  by  a  prolongation  of  the  curve,  especially  of  the 
phase  of  relaxation,  this  does  not  hold  for  mammalian  muscle.  In  the  latter 
muscle  the  successive  contractions  become  smaller  as  fatigue  sets  in,  but  their 
duration  is  not  increased. 

The  Contraction  Wave. — Under  ordinary  conditions  the  fibers 
of  a  muscle  when  stimulated  contract  simultaneously  or  nearly  so, 
and  the  whole  extent  of  the  muscle  is  practically  in  the  same  phase 
of  contraction  at  a  given  instant.  It  is  comparatively  easy  to 
show,  however,  that  the  process  of  contraction  spreads  over  the 
fibers,  from  the  point  stimulated,  in  the  form  of  a  wave  which  moves 
with  a  definite  velocity.  In  a  long  muscle  with  parallel  bundles  of 
fibers  one  may  prove,  by  proper  recording  apparatus,  that  if  the 
muscle  is  stimulated  at  one  end  a  point  near  this  end  enters  into 
contraction  before  a  point  farther  off.  Knowing  the  difference  in 
time  between  the  appearance  of  the  contraction  at  the  two  points 
and  the  distance  apart  of  the  latter,  we  have  the  data  for  determin- 
ing the  velocity  of  its  propagation.  In  frog's  muscles  this  velocity 
is  found  to  be  equal  to  3  or  4  meters  per  second,  while  in  human 
muscle,  at  the  body  temperature,  it  is  estimated  at  10  to  13  meters 
per  second.  Knowing  the  time  it  takes  this  wave  to  pass  a  given 
point  (d)  and  its  velocity  (v),  its  entire  length  is  given  by  the 
formula  I  =  vd.  In  the  frog's  muscle,  therefore,  with  a  velocity  of 
3000  mm.  per  second,  and  a  duration  of,  say,  0.1  second,  the 
product  (3000X0.1=300  mms.)  gives  the  length  of  the  wave  or 
the  length  of  muscle  which  is  in  some  phase  of  contraction  at  any 
given  instant.  Under  normal  conditions  the  muscle  fibers  are 
stimulated  through  their  motor  plates,  which  are  situated  toward 
the  middle  of  the  fiber,  or  perhaps  one  muscle  fiber  may  have 
two  or  more  motor  plates,  giving  two  or  more  points  of  stimula- 
tion. It  follows,  therefore,  from  this  anatomical  arrangement 
and  the  great  velocity  of  the  wave  that  all  parts  of  the  fibers 
are  in  contraction  at  the  same  instant  and,  indeed,  in  nearly  the 
same  phase  of  contraction.  Under  abnormal  conditions  muscles 
may  exhibit  fibrillar  contractions;  that  is,  separate  fibers  or  bundles 
of  fibers  contract  and  relax  at  different  times,  giving  a  flickering, 
trembling  movement  to  the  muscle. 


THE    PHENOMENON    OF    CONTRACTION.  37 

Idiomuscular  Contractions. — In  a  fatigued  or  moribund  muscle  mechan- 
ical stimulation  may  give  a  localized  contraction  which  does  not  spread  or 
spreads  very  slowly,  showing  that  the  abnormal  changes  in  the  muscle  prevent 
the  excitation  from  traveling  at  its  normal  velocity.  A  localized  contraction 
of  this  kind  was  designated  by  Schiff  as  an  idiomuscular  contraction.  It  may 
be  produced  in  the  muscle  of  a  dying  or  recently  dead  animal  by  localized 
mechanical  stimulation,  as  by  drawing  a  blunt  instrument — e.  g.,  the  handle 
of  a  scalpel — across  the  belly  of  the  muscle.  The  point  thus  stimulated  stands 
out  as  a  wheal,  owing  to  the  idiomuscular  contraction. 

The  Energy  Liberated  in  the  Contraction. — When  a  muscle 
contracts,  energy  is,  as  we  say,  liberated  in  several  forms,  and 
can  be  measured  quantitatively.  First,  there  is  a  production  of 
heat,  which  is  indicated  by  a  rise  in  temperature  of  the  muscle.* 
According  to  Heidenhain,  the  temperature  of  the  frog's  muscle 
is  increased  in  a  single  contraction  by  0.001°  C.  to  0.005°  C.  Larger 
muscles,  such  as  those  of  the  thigh  of  the  dog,  when  repeatedly 
stimulated  may  cause  a  rise  of  temperature  of  from  1°  to  2°  C. 
The  thermometer  does  not,  of  course,  measure  the  amount  of  heat 
produced,  but  only  the  temperature  of  the  muscle.  Heat  is  esti- 
mated quantitatively  in  terms  of  calories.  By  a  calorie  is  meant 
the  quantity  of  heat  necessary  to  raise  1  gm.  of  water  1°  C. 
Knowing  the  specific  heat  and  weight  of  muscle,  we  can  readily 
calculate  the  number  of  calories  produced.  Thus,  if  a  frog's 
muscle  weighing  2  gms.  shows  a  rise  of  temperature  of  0.005°  C. 
from  a  single  contraction  the  production  of  heat  in  calories  is  given 
by  multiplying  the  weight  of  the  muscle  by  its  specific  heat, 
0.83,  to  reduce  it  to  an  equivalent  weight  of  water,  and  this 
product  by  the  rise  in  temperature:  2  X  0.83  X  0.005  =  0.0083 
calorie.  The  fact  that  muscular  exercise  increases  the  produc- 
tion of  heat  in  the  body  is  a  matter  of  general  observation.  Making 
use  of  a  very  sensitive  thermo-couple,  Hillt  has  been  able  to 
register  the  production  of  heat  in  an  excised  frog's  muscle.  In  the 
case  of  a  simple  contraction  or  twitch,  the  production  of  the  heat 
is  practically  instantaneous,  indicating  an  underlying  chemical 
change  of  explosive  suddenness.  Analyses  of  the  galvanometric 
records  obtained  in  these  experiments  show  that  there  is  also  a 
delayed  heat  production  which  occurs  after  the  contraction  is 
over.  We  may  say,  in  fact,  that  the  result  of  a  stimulus  causing  a 
contraction  is  to  set  up  two  processes,  each  of  which  leads  to  the 
development  of  heat.  The  heat  produced  in  the  first  process  is 
detectible  during  the  contraction,  while  that  caused  by  the  second 
process  is  subsequent  to  the  act  of  shortening  and,  therefore,  is. 
not  directly  connected  with  the  changes  leading  to  contraction. 
The  significance  of  this  delayed  heat  production  will  be  referred  to> 
in  connection  with  the  chemical  changes  of  contraction  and  the 

*  For  general  discussion,  see  Tigerstedt  in  Winterstein's  "Handbuch  cL 
vergleich.  Physiologic." 

t  Hill,  "Journal  of  Physiology,"  40,  389,  1910;  46,  28,  1913. 


38         THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE. 

theories  of  muscle  contraction.  Second.  Some  electrical  energy 
is  developed  during  the  contraction.  The  means  of  detecting 
and  measuring  this  energy  will  be  described  in  a  subsequent  chapter. 
Considered  quantitatively,  the  amount  is  small.  Third.  Work 
is  done  if  the  muscle  is  allowed  to  shorten  during  the  contraction. 
By  work  is  meant  external  or  useful  work  —  that  is,  the  muscle  lifts 
a  weight  or  overcomes  an  opposing  resistance.  If  a  muscle  con- 
tracts against  a  weight  too  heavy  to  be  lifted,  or  a  resistance  too 
strong  to  be  overcome,  it  does  no  external  work,  although,  of 
course,  much  energy  is  liberated  as  heat  or,  as  it  is  sometimes  called, 
internal  work.  The  work  done  by  a  muscle  during  contraction  is 
measured  in  the  usual  mechanical  units,  by  the  product  of  the 
load  into  the  lift.  That  is,  if  a  muscle  lifts  a  weight  of  40  grams 
to  a  height  of  10  millimeters,  the  work  done  is  40  X  10  =  400 
gram-millimeters,  or  0.4  grammeter.  We  can  in  calculations 
convert  external  work  into  heat  or  internal  work  by  making  use 
of  the  ascertained  mechanical  equivalent  of  heat,  according  to 
which  1  calorie  =  426.5  grammeters  of  work.  The  work,  0.4 
grammeter,  supposed  to  be  done  in  the  above  experiment,  would  be 
equivalent,  therefore,  to  0.4  -=-  426,  or  about  0.001  of  a  calorie. 

The  Efficiency  of  the  Muscle  as  a  Work  Machine.  —  In  any 
engine  constructed  to  perform  external  work  it  is  desirable  to  know 
what  efficiency  the  engine  exhibits,  that  is  to  say,  what  per  cent,  of 
the  total  energy  given  to  the  engine  or  developed  in  the  engine  may 
be  obtained  as  external  or  mechanical  work.  If  we  represent  by  Q 
the  total  energy  developed  and  by  W  the  energy,  expressed  in  the 
same  unit,  obtained  as  work,  then  the  efficiency  E  is  given  by  the 
formula 


Numerous  experiments  to  determine  this  value  have  been  made 
upon  the  isolated  muscles  of  frogs.  These  muscles  can  be  taken 
from  the  body,  be  made  to  contract  under  different  loads  by  arti- 
ficial stimuli,  and  the  work  done  and  the  heat  developed  can  both 
be  measured  with  considerable  accuracy.  The  earlier  experiments 
of  this  kind  indicated  that  the  frog's  muscle  under  optimum  condi- 
tions may  exhibit  an  efficiency  as  high  as  25  to  30  per  cent.,  as  is 
shown  by  the  following  example  taken  from  Fick's  investigations:* 

Load.  Heat  Developed.      Mechanical  Work.      Thermal  llquivalent  Efficiency. 

200  gm.        25.6  microcalories.       2905  gm.-mm.         6.83  microcalories.  '     •  =  26+  %. 

Experiments  have  shown  that  the  efficiency  of  different  muscles 
in  the  same  animal  varies  or  may  vary,  and  likewise  the  efficiency 
*  Fick,  "Pfliiger's  Archiv,"  16,  58,  1878. 


THE    PHENOMENON    OF    CONTRACTION. 


39 


of  the  same  muscle  under  different  nutritive  conditions.  Many 
observations  of  a  similar  character  have  been  carried  out  upon  man 
when  doing  muscular  work  of  various  sorts,  such  as  mountain 
climbing,  bicycle  riding,  etc.  In  such  experiments  the  total 
energy  given  off  during  the  work  may  be  estimated  by  the  methods 
of  direct  or  of  indirect  calorimetry  (p.  960).  In  the  former  case 
the  heat  produced  in  the  body  is  determined  directly,  in  the  latter 
case  it  is  estimated  on  the  basis  of  the  amount  of  material  con- 
sumed. The  body  at  rest  produces  constantly  a  certain  amount  of 
heat  which  can  be  measured.  In  determining  the  efficiency  of 
the  human  muscles  in  work  the  heat  production  during  rest  is 
subtracted  from  the  heat  production  during  work,  the  difference 
giving  the  new  energy  developed  in  the  muscles  during  work. 
Thus,  for  example,  in  experiments  made  at  the  Nutrition  Labora- 
tory of  the  Carnegie  Institution  results  of  this  kind  were  obtained:* 


HEAT  PRODUCED 

M€Bcu£\RAWoR<°*         HEAT  PRODUCED.             .OVER  RESTING 

NET  EFFICIENCY. 

METABOLISM. 

Calories. 

Calories. 

Calories. 

Per  cemt. 

569 

3959 

2619 

21.7 

601 

4139 

2799 

21.5 

538 

3834 

2494 

21.6 

657 

4309 

2969 

22.1 

663 

4056 

2716 

20.7 

587 

4131 

2791 

21.0 

The  average  results  of  such  experiments  show  an  efficiency  of 
about  21  per  cent.,  which  compares  favorably  with  the  figures  ob- 
tained for  mechanical  engines,  such  as  the  steam  engine  (15  to  25 
per  cent.) .  It  must  not  be  assumed,  however,  from  this  comparison 
of  the  muscle  with  a  steam  engine  that  in  the  former,  as  in  the 
latter,  there  is  a  conversion  of  part  of  the  heat  to  mechanical  work. 
This  view  was  held  formerly  in  physiology,  but  considerations, 
which  are  referred  to  below  (p.  73),  have  convinced  most  physiol- 
ogists that  the  muscle  is  not  a  heat  engine.  The  energy  that  is 
expressed  as  work  is  derived  in  some  other  as  yet  undetermined 
way.  Nevertheless,  heat  is  evolved  by  chemical  changes  and 
material  is  consumed  in  muscular  contraction  as  an  apparently 
necessary  part  of  the  process,  and  the  work  performed  bears  to 
this  energy  liberated  as  heat  the  proportion  indicated. 

The  Curve  of  Work  and  the  Absolute  Power  of  a  Muscle. — 
The  statements  in  the  preceding  paragraph  prove  that  the  muscle, 
judged  from  the  standpoint  of  a  machine  to  do  work,  compares  most 

*  Benedict  and  Cathcart,  "Muscular  Work — The  Efficiency  of  the  Human 
Body  as  a  Machine,"  Carnegie  Institution,  1913. 


40  THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 

favorably  in  its  efficiency  with  machinery  of  human  construction. 
But  it  should  be  borne  in  mind  that  in  this  as  in  other  respects  the 
properties  of  cross-striated  muscular  tissues  vary  greatly.  In  some 
animals  or  individuals  it  is  a  much  more  efficient  machine  than  in 
others.  This  fact  is  indicated  by  our  general  experience  regarding 
variations  in  muscular  strength  in  different  individuals,  and  is 
proved  more  precisely  by  direct  experiments  on  single  muscles.  A 
frog's  muscle  may  be  isolated  and  the  extent  of  its  contractions  and 
the  work  done  may  be  estimated  directly.  Under  such  conditions  it 
will  be  found  that,  while  the  height  of  the  successive  contractions 
diminishes  as  the  load  increases  (see  Fig.  17),  the  work  done — that 


Fig.  17. — To  show  the  decrease  in  extent  of  contraction  of  the  gastrocnemius  muscle 
of  a  frog  with  increase  in  load.  In  the  first  contraction,  to  the  right,  the  load  was  14.2 

EAt  each  successive  contraction  the  load  was  increased  by  5.3  gms.     With  a  load  of 
?ms.  the  lever  gave  only  the  slightest  indication  of  a  shortening,  and  this  may  have 
due  to  some  lateral  movement. 

is,  the  product  of  the  load  into  the  lift — first  increases  and  then 
decreases.    For  example : 

Work  Done  in  Gram-millimeters, 
Load  in  Grams.  Lift  in  Millimeters.  Load  X  Lift. 

5  27.6  138.0 

15  25.1  376.5 

25  11.45  286.25 

35  6.3  220.5        ^ 

A  series  of  experiments  of  this  kind  furnishes  data  for  'con- 
structing a  curve  of  work  by  plotting  off  along  the  abscissa  at  equal 
intervals  the  equal  increments  in  load  and  erecting  over  each  load 
an  ordinate  showing  the  proportional  amount  of  work  done.  The 
curve  has  the  general  form  indicated  in  Fig.  18.  Three  facts  are 
expressed  by  this  curve:  First,  that  if  the  muscle  lifts  no  weight 
no  work  will  be  done;  this  follows  theoretically  from  the  formula 


THE    PHENOMENON    OF    CONTRACTION.  41 

W  =  L  H f  in  which  W  represents  the  work  done,  L  the  load,  and 
H  the  lift.  If  either  L  or  H  is  equal  to  zero  the  product,  of  course, 
is  zero;  that  is,  no  external  work  is  done;  the  chemical  energy 
liberated  in  the  contraction  takes  the  form  of  heat.  Second. 
There  is  an  optimum  load  for  each  muscle  with  which  the  greatest 
proportion  of  work  can  be  obtained.  Third.  When  the  load  is  just 
sufficient  to  counteract  the  contraction  of  the  muscle  no  work  is 
done,  H  in  the  above  formula  being  zero.  This  amount  of  load 
measures  wrhat  Weber  called  the  absolute  power  of  the  muscle. 
As  will  be  seen  from  the  above  curve,  it  is  measured  by  the 


Fig.  18. — The  curve  of  work  obtained  by  plotting  the  results  shown  in  Fig.  17.  The 
initial  contraction  was  made  with  a  load  of  14.2  gms.,  and  the  work  done  in  gram-milli- 
meters is  represented  by  the  ordinate  erected  at  this  point.  The  maximum  work  was  done 
with  a  load  of  88.6  gms.,  and  the  absolute  power  of  this  particular  muscle  was  found  to  be 
equal  to  182  gms. 

weight  which  the  muscle  cannot  lift  and  which,  on  the  other 
hand,  cannot  cause  any  extension  of  the  muscle  while  contracting. 
Or,  in  more  general  terms  (Hermann),  the  absolute  power  of  a 
muscle  is  the  maximum  of  tension  which  it  can  reach  without 
alteration  of  its  natural  length.  This  absolute  power  can  be 
measured  for  the  muscles  of  different  animals  and  for  convenience 
of  comparison  can  then  be  expressed  in  terms  of  the  cross-area 
of  the  muscle  given  in  square  centimeters.  Weber  has  shown 
that  the  absolute  power  of  a  muscle  varies  with  the  cross-area,  since 
this  depends  upon  the  number  of  constituent  fibers  whose  united 
contraction  makes  the  contraction  of  the  muscle.  Expressed  in 


42  THE    PHYSIOLOGY    OF    MUSCLE   AND    NERVE. 

this  way,  it  is  found  that  the  absolute  power  of  human  muscle  is, 
size  for  size,  much  greater  than  that  of  frog's  muscle.  For  in- 
stance, the  absolute  power  of  a  frog's  muscle  of  1  square  centimeter 
cross-area  is  estimated  at  from  0.7  kilogram  to  3  kilograms,  while 
that  of  a  human  muscle  of  the  same  size  is  estimated  by  Hermann 
at  6.24  kilograms.  Taken  as  a  whole,  the  human  muscle  is  a  better 
machine  for  work,  but  it  seems  possible,  although  exact  figures  are 
lacking,  that  the  absolute  power  of  the  muscles  of  some  insects 
reckoned  for  the  same  unit  of  cross-area  would  be  much  greater 
than  in  human  muscle. 

COMPOUND  OR  TETANIC  CONTRACTIONS. 

Definition  of  Tetanus  — When  a  muscle  receives  a  series  of 
rapidly  repeated  stimuli  it  remains  in  a  condition  of  contraction  as 
long  as  the  stimuli  are  sent  in  or  until  it  loses  its  irritability  from 
the  effect  of  fatigue.  A  contraction  of  this  character  is  described 
as  a  compound  contraction  or  tetanus.  If  the  stimuli  follow  each 
other  with  sufficient  rapidity  the  muscle  shows  no  external  sign  of 
relaxation  in  the  intervals  between  stimuli,  and  if  its  contractions 
are  recorded  upon  a  kymographion  by  means  of  an  attached  lever 
a  curve  is  obtained  such  as  is  shown  at  5  in  Fig.  19.  A  con- 
traction of  this  character  is  described  as  a  complete  tetanus.  If, 
however,  the  rate  of  stimulation  is  not  sufficiently  rapid  the  mus- 
cle will  relax  more  or  less  after  each  stimulus  and  its  recorded 
curve,  therefore,  will  present  the  appearance  shown  in  1,  2  3,  and  4 
of  Fig.  19.  A  tetanus  of  this  character  is  described  as  an  incom- 
plete tetanus.  It  is  obvious  that  according  to  the  rate  of  stimu- 
lation there  may  be  numerous  degrees  of  incomplete  tetanus,  as 
shown  in  Fig.  19,  extending  from  a  series  of  separate  single  con- 
tractions, on  the  one  hand,  to  a  perfect  fusion  of  the  contractions, 
a  complete  tetanus,  on  the  other.  Tetanic  contractions  present 
two  peculiarities  in  addition  to  the  mere  matter  of  duration, 
which  is  governed,  of  course,  by  the  duration  of  the  stimu- 
lation: First,  the  more  or  less  complete  fusion  of  the  contrac- 
tions due  to  the  separate  stimuli.  This,  as  stated  above,  is  the 
distinctive  sign  of  a  tetanus.  Second,  the  phenomenon  of  sum- 
mation in  consequence  of  which  the  total  shortening  of  the  muscle 
in  tetanus  may  be  considerably  greater  than  that  caused  by  a 
maximal  simple  contraction. 

Summation. — The  facts  of  summation  may  be  shown  most  read- 
ily by  employing  a  device  to  send  into  the  muscle  two  successive 
stimuli  at  varying  intervals.  If  the  second  stimulus  falls  into  the 
muscle  at  the  apex  of  the  contraction  caused  by  the  first  stimulus, 
then,  even  if  the  first  contraction  is  maximal,  the  muscle  will  shorien 
still  farther;  the  first  and  second  contractions  are  summated,  giv- 


THE    PHENOMENON    OF    CONTRACTION 


43 


ing  a  total  shortening  greater  than  can  be  obtained  by  a  single  stim- 
ulus (see  Fig.  20).  The  extent  of  the  summation  in  such  cases 
varies  with  a  number  of  conditions,  such  as  the  intervals  between  the 


Fig.  19. — Analysis  of  tetanus.  Experiment  made  upon  the  gastrocnemius  muscle  of  a 
frog  to  show  that  by  increasing  the  rate  of  stimulation  the  contractions,  at  first  separate 
(1),  fuse  more  and  more  through  a  series  of  incomplete  tetani  (2,  3,  4)  into  a  complete  tetanus 
(5)  in  which  there  is  no  indication,  so  far  as  the  record  goes,  of  a  separate  effect  for  each 
Stimulus. 

stimuli,  the  relative  strengths  of  the  stimuli,  the  load  carried  by  the 
muscle,  etc.  Taking  the  simplest  conditions  of  a  moderately  loaded 
muscle  and  two  maximal  stimuli,  it  is  found  that  the  greatest  sum- 


44  THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE. 

mation  occurs  when  the  stimuli  are  so  spaced  that  the  second  con- 
traction begins  at  the  apex  of  the  first.  If  the  stimuli  are  closer  to- 
gether, so  that,  for  instance,  the  second  contraction  follows  shortly 
after  the  first  has  begun,  the  total  shortening  is  less,  and  the  same  is 
true  to  an  increasing  extent  as  the  second  contraction  falls  later 
and  later  in  the  period  of  relaxation  after  the  first  contraction.*  If 
instead  of  two  we  use  three  successive  stimuli,  falling  into  the  muscle 
at  proper  intervals,  a  still  further  summation  occurs.  In  this  way 
the  total  extent  of  shortening  in  a  muscle  completely  tetanized  may 
be  several  times  as  great  as  that  of  a  single  maximal  contraction. 

The  Discontinuous  Character  of  the  Tetanic  Contraction 
— The  Muscle-tone. — In  complete  tetanus  the  muscle  seems  to 
be  in  a  condition  of  continuous  uniform  contraction;  the  re- 


Fig.  20. — Summation  of  two  successive  contractions.  Curve  1  shows  a  simple  con- 
traction due  to  a  single  stimulus,  the  latent  period  being  indicated  at  the  beginning  of  the 
contraction.  Curve  2  shows  the  summation  due  t©  two  succeeding  stimuli. 

corded  curve  shows  no  sign  of  relaxation  between  stimuli  and  no 
external  indication,  in  fact,  that  the  separate  stimuli  do  more  than 
maintain  a  state  of  uniform  contraction.  It  can  be  shown,  how- 
ever, that  in  reality  each  stimulus  has  its  own  effect,  and  that  the 
chemical  changes  underlying  the  phenomenon  of  contraction 
form  an  interrupted  series  corresponding,  within  limits,  to  the 
series  of  stimuli  sent  in.  The  clearest  proof  for  this  belief 
is  found  in  the  electrical  changes  that  result  from  each  stimulus, 
and  the  facts  relating  to  this  side  of  the  question  will  be  stated 
subsequently  in  the  chapter  on  The  Electrical  Phenomena 
of  Muscle  and  Nerve.  Another  proof  is  found  in  the  phenome- 
non of  the  muscle-tone.  When  a  muscle  is  stimulated  directly 
or  through  its  motor  nerve  a  musical  note  may  be  heard  by 
*  Von  Kries,  "Archiv  fur  Physiologic,"  1888,  p.  537. 


THE    PHENOMENON    OF    CONTRACTION.  45 

applying  the  ear  or  a  stethoscope  to  the  muscle.  The  note  that 
is  heard  corresponds  in  pitch,  up  to  a  certain  point,  with  the  num- 
ber of  stimuli  sent  in, — that  is,  the  muscle  vibrates,  as  it  were,  in 
unison  with  the  number  of  stimuli,  and,  although  the  vibrations 
are  not  sufficient  to  affect  the  recording  lever,  they  can  be  heard 
as  a  musical  note.  This  fact,  therefore,  may  be  taken  as  a  proof 
that  during  complete  tetanus  there  is  a  discontinuous  series  of 
changes  in  the  muscle  the  rate  of  which  corresponds  with  that  of  the 
stimulation.  The  series  of  electrical  changes  corresponding  with  the 
series  of  stimuli  sent  in  may  be  made  audible  by  applying  i  telephone 
to  the  muscle.  Making  use  of  this  method,  Wedenski*  has  shown 
that  the  ability  of  the  muscle  to  respond  isorhythmically  to  the 
rate  of  stimulation  is  limited.  In  frog's  muscle  the  pitch  of  the 
musical  tone  may  correspond  with  the  rate  of  stimulation  up  to 
about  200  stimuli  per  second.  In  the  muscle  of  the  warm-blooded 
animal  the  correspondence  may  extend  to  about  1000  stimuli  per 
second.  If  the  rate  of  stimulation  is  increased  beyond  these 
limits  the  musical  note  heard  does  not  correspond,  but  falls 
to  a  lower  pitch,  indicating  that  some  of  the  stimuli  under  these 
conditions  become  ineffective.  It  should  be  added  that  the  high 
figures  given  above  for  the  correspondence  between  the  stimuli  and 
the  muscle-tone  hold  good  only  for  entirely  fresh  preparations. 
The  lability  of  the  muscle  quickly  becomes  less  as  it  is  fatigued ;  so 
that  in  the  frog,  for  instance,  the  correspondence  in  long-continued 
contractions  is  accurate  only  when  the  rate  of  stimulation  does 
not  exceed  30  per  second. 

The  Number  of  Stimuli  Necessary  for  Complete  Tetanus. — 
The  number  of  stimuli  necessary  to  produce  complete  tetanus 
varies,  as  we  should  expect,  with  the  kind  of  muscle  used  and  in 
accordance  with  the  rapidity  of  the  process  of  relaxation  shown 
by  these  muscles  in  simple  contractions.  The  series  that  may  be 
arranged  to  demonstrate  this  variation  is  quite  large,  extending 
from  a  supposed  rate  of  300  per  second  for  insect  muscle  to  a  low 
limit  of  one  stimulus  in  5  to  7  seconds  for  plain  muscle.  The  frog's 
muscle  goes  into  complete  tetanus  with  a  rate  of  stimulation  of 
from  20  to  30  per  second.  Inasmuch  as  the  rapidity  of  relaxation 
of  the  muscle  is  much  retarded  by  certain  influences,  such  as  a 
low  temperature  or  fatigue,  it  follows  that  these  same  influences 
affect  in  a  corresponding  way  the  rate  of  stimulation  necessary  to 
give  complete  tetanus.  A  frog's  muscle  stimulated  at  the  rate  of 
10  stimuli  per  second  may  record  an  incomplete  tetanus,  but  if  the 
stimulus  is  maintained  for  some  time  the  tetanus  finally  becomes 
complete  in  consequence  of  the  slowing  of  the  phase  of  relaxation, 

*  Wedenski,  "  Du  rhythme  musculaire  dans  la  contraction  nonnale," 
"  Archives  de  physiologic,"  1891,  p.  58. 


46         THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE. 

or,  another  way  of  looking  at  the  matter,  in  consequence  of  the 
development  of  that  condition  of  maintained  contraction  which 
has  been  spoken  of  above  as  contracture. 

Voluntary  Contractions. — After  ascertaining  that  muscles  may 
give  either  simple  or  tetanic  contractions  one  asks  naturally 
whether  in  our  voluntary  movements  we  can  also  obtain  both 
sorts  of  contractions.  In  the  first  place,  it  is  obvious  that  most 
of  our  voluntary  movements  are  too  long  continued  to  be  simple 
contractions.  The  time  element  alone  would  place  them  in  the 
group  of  tetanic  contractions,  and  this  is  the  usual  conclusion 
regarding  them.  In  voluntary  movements  a  neuromuscular 
mechanism  comes  into  play.  This  mechanism  consists,  on  the 
motor  side,  of  at  least  two  nerve  units  or  neurons  and  the  muscle, 
as  indicated  in  the  accompanying  diagram  (Fig.  21).  If  in  ordi- 
nary voluntary  movements  the  muscular  contractions  are  tetanic, 
we  must  suppose  that  the  motor  nerve  cells  discharge  a  series  of 
nerve  impulses  through  the  motor  nerve  into  the  muscle.  The 
contraction  of  voluntary  muscle  has  been  investigated,  therefore, 
in  various  ways  to  ascertain  whether  there  is  any  objective  indica- 
tion of  the  number  of  separate  contractions  that  are  fused  together 
to  make  this  normal  tetanus.  Various  methods  have  been  em- 
ployed. The  contractions  of  the  muscle  have  been  recorded  by 
means  of  levers  or  tambours,  so  as  to  give  a  curve  which  can  be 
analyzed;  the  vibrations  of  the  muscle  have  been  estimated  on  the 
principle  of  sympathetic  resonance,  and  the  musical  tone  emitted 

by  the  muscle  during  contrac- 
tion has  been  determined. 
The  estimates  arrived  at  by 
these  several  methods  all  indi- 
cated a  relatively  slow  rhythm 
of  stimulation  approximating 
a  rate  of  20  stimuli  per  second. 
The  whole  subject  has  been 
reinvestigated  more  recently 
by  employing  the  "string 
galvanometer"  (see  p.  99)  to 
record  the  number  of  electrical 
variations  occurring  during  a 
voluntary  contraction.  Since 

Fig.  21. — Schema  to  show  the  mnerva-  J 

tion  of  the  skeletal  (voluntary)  muscles:    1,  each    Separate     stimulus    to    a 
the  intercentral  (pyramidal)  neuron :    2,  the  i  -,.    , . 

spinal  neuron;  3,  the  muscle.  HlUSCle   CaUSCS  a  distinct 


trical  variation,  it  is  evident 

that  if  we  can  record  the  number  of  such  variations  per  second  we 
shall  have  almost  conclusive  evidence  as  regards  the  number  of 
simple  contractions  which  enter  into  the  production  of  voluntary 


THE  PHENOMENON  OF  CONTRACTION. 


47 


tetanus.  The  string  galvanometer  lends  itself  to  this  purpose  better 
than  any  form  of  electrometer  yet  devised,  and  Piper,*  by  the  use 
of  this  instrument,  finds  that  in  voluntary  contractions  of  the  flexor 
muscles  of  the  arms  or  fingers  the  series  of  electrical  variations  fol- 
lows at  the  rate  of  47  to  50  per  second.  Increase  in  strength  of  con- 
traction in  these  muscles  causes  no  change  in  rate,  although  a  cor- 
responding variation  in  the  intensity  of  the  electrical  changes  is 
observed.  When  different  muscles  are  studied  by  this  method, 
quite  a  marked  difference  in  rate  is  obtained.  Piper  reports  such 
observations  as  the  following:  M.  deltoideus,  58  to  62;  M.  gas- 
trocnemius  and  M.  tibialis  anterior,  42  to  44;  M.  quadriceps 
femoris,  38  to  41;  M.  massefer,  88  to  100,  and  M.  temporalis,  80 
to  86.  Assuming  that  these  figures  represent  the, rate  of  dis- 
charge of  nerve  impulses  per  second  by  the  nerve  cells  from 


Fig.  22. — The  upper  curve  shows  the  vibrations  of  the  "string"  of  the  string  gal- 
vanometer during  voluntary  contraction  of  the  flexor  of  the  fingers.  Each  vibration  is 
due  to  an  electrical  oscillation  in  the  muscle  (action  current).  These  oscillations  occur  at 
the  rate  of  50  per  second,  as  may  be  seen  by  reference  to  the  lower  curve,  the  breaks  in  which 
indicate  fifths  of  a  second.  This  fact  would  indicate,  therefore,  that  in  the  voluntary  con- 
traction we  have  a  tetanus  composed  of  single  contractions  following  at  the  rate  of  50  par 
second. — (From  Piper.) 

which  arise  the  motor  fibers  to  the  muscles  named,  it  is  evident 
that  the  various  spinal  and  cranial  motor  centers  may  possess 
quite  widely  different  rhythms,  although  for  each  particular 
center  the  rate  is  more  or  less  fixed.  Among  the  motor  centers 
thus  far  studied  it  will  be  noted  that  the  cells  of  the  N.  trigeminus 
possess  the  highest  rate  of  discharge.  There  has  been  much 
discussion  as  to  whether  or  not  we  can  obtain  simple  as  well  as 
compound  contractions  by  voluntary  stimulation  of  our  muscles. 
It  has  been  pointed  out  that  in  very  rapid  contractions,  such  as 
occur  in  the  trilling  movements  of  the  fingers  in  playing  the 
piano,  the  duration  of  the  separate  contractions  is  so  brief  as  to 
suggest  that  they  may  be  of  the  order  of  simple  contractions. 
Direct  investigation  of  such  movements  by  the  older  method 

*Piper,  Pfltiger's  "Archiv  f.  d.  ges.  Physiologie,"  1907,  119,  301;  "Zeit- 
schrift  f.  Biologic,"  1908,  50,  393  and  504;  "Archiv  fur  Physiologie,"  1914, 
345. 


48         THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE. 

of  recording  with  levers  (von  Kries)  or  by  the  newer  method  of 
photographing  the  electrical  oscillations  shows,  on  the  contrary, 
that  even  the  shortest  possible  voluntary  contractions  are  brief 
tetani  made  up  of  a  short  lasting  series  of  contractions  fused 
together.  In  all  probability,  therefore,  our  motor  centers,  when- 
ever they  are  stimulated  by  a  so-called  act  of  the  will,  discharge 
rhythmically  a  series  of  nerve  impulses.  As  we  shall  see  later, 
it  is  possible  that  certain  of  these  centers,  when  stimulated 
reflexly,  may  discharge  a  single  nerve  impulse  and  thus  arouse 
a  simple  muscular  contraction  (see  Knee- kick). 

The  Ergograph. — Voluntary  contractions  in  man  may  be  re- 
corded in  a  great  many  ways,  but  Mosso  has  devised  a  special  in- 
strument for  this  purpose,  known  as  the  ergograph.  It  has  been 
much  used  in  quantitative  investigations  upon  muscular  work 
and  the  conditions  influencing  it.  The  apparatus  is  shown  and 
described  in  Fig.  23.  The  person  experimented  upon  makes  a 
series  of  short  contractions  of  the  flexor  muscle  of  the  middle 
finger,  thereby  lifting  a  known  weight  to  a  definite  height 
which  is  recorded  upon  a  drum.  In  a  set  of  experiments  the 
rate  of  the  series  of  contractions — that  is,  the  interval  of  rest 
between  the  contractions — is  kept  constant,  as  also  is  the  load  lifted. 
Under  these  conditions  the  contractions  become  less  and  less  exten- 
sive as  fatigue  comes  on,  and  finally,  with  the  strongest  voluntary 
effort,  the  contraction  of  the  muscles  is  insufficient  to  lift  the  weight. 
In  this  way  a  record  is  obtained  such  as  is  shown  in  Fig.  24.  In 
such  a  record  we  can  easily  calculate  the  total  work  done  by 
obtaining  the  product  of  the  load  into  the  lift  for  each  contrac- 
tion and  adding  these  products  together.  By  this  means  the 
capacity  for  work  of  the  muscle  used  can  be  studied  objectively 
under  varying  conditions,  and  many  suggestive  results  have  been 
obtained,  some  of  which  will  be  referred  to  specifically.*  It  should 
be  borne  in  mind,  however,  that  the  ergograph  in  this  form  does 
not  enable  us  to  compute  the  total  work  that^the  muscle  is  capable 
of  performing.  It  is  obvious  that  when  the  point  of  complete 
fatigue  is  reached,  as  illustrated  in  the  record,  Fig.  24,  the  muscle  is 
still  capable  of  doing  work,  that  is  external  work,  if  we  replace  the 
heavy 'load  by  a  lighter  one.  For  this  reason  some  investigators 
have  substituted  a  spring  in  place  of  the  load,f  giving  thus  a 
spring  ergograph  instead  of  a  weight  ergograph.  Although  with  the 
spring  ergograph  every  muscular  contraction  is  recorded  and  the 
entire  work  done  may  be  calculated,  it  also  possesses  certain  theo- 

*  Mosso,  "Archives  italiennes  de  biologie,"  13,  187,  189;  also  Maggiora, 
1890,  p.  191,  342.  Lombard,  "Journal  of  Physiology,"  13,  1,  1892. 

t  Franz,  "American  Journal  of  Physiology,"  4,  348,  1900;  also  Hough, 
ibid.,  5,  240,  1901. 


THE    PHENOMENON    OF    CONTRACTION. 


49 


retical  and  practical  disadvantages,  for  a  discussion  of   which 
reference  must  be  made  to  the  authors  quoted. 


Fig.  23. — Mosso's  ergograph:  c  is  the  carriage  moving  to  and  fro  on  runners  by  means 
of  the  cord  d,  which  passes  from  the  carriage  to  a  holder  attached  to  the  last  two  phalanges 
of  the  middle  finger  (the  adjoining  fingers  are  held  in  place  by  clamps) ;  p,  the  writing  point 
of  the  carriage,  c,  which  makes  tne  record  of  its  movements  on  the  kymographion ;  w,  th» 
weight  to  be  lifted. 


Fig.  24.  — Normal  fatigue  curve  of  the  flexors  of  the  middle  finger  of  right  hand.     Weignt, 
3  kilograms,  contractions  at  intervals  of  two  seconds. — (Maggivra.) 

The  weight  ergograph  has,  so  far  at  least,  given  us  the  most  sug-« 
gestive  results.     Among  these  the  following  may  be  mentioned: 
4 


50          THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE. 

(1)  If  a  sufficient  interval  is  allowed  between  contractions  no  fatigue 
is  apparent.  With  a  load  of  6  kilograms,  for  instance,  the  flexor 
muscle  (M.  flexor  digitorum  suUimis)  showed  no  fatigue  when  a 
rest  of  10  seconds  was  given  between  contractions.  (2)  After 
complete  fatigue  with  a  given  load  a  very  long  interval  (two 
hours)  is  necessary  for  the  muscle  to  make  a  complete  recovery 
and  give  a  second  record  as  extensive  as  the  first.  (3)  After 
complete  fatigue  efforts  to  still  further  contract  the  muscle 
greatly  prolong  this  period  of  complete  recovery, — a  fact  that 
demonstrates  the  injurious  effect  of  straining  a  fatigued  muscle. 
(4)  The  power  of  a  muscle  to  do  work  is  diminished  by  conditions 
that  depress  the  general  nutritive  state  of  the  body  or  the  local 
nutrition  of  the  muscle  used;  for  instance,  by  loss  of  sleep, 
hunger,  mental  activity,  anemia  of  the  muscle,  etc.  (5)  On  the 
contrary,  improved  circulation  in  the  muscle — produced  by 
massage,  for  example — increases  the  power  to  do  work.  Food 
also  has  the  same  effect,  and  some  particularly  interesting 
experiments  show  that  sugar,  as  a  soluble  and  easily  absorbed 
foodstuff,  quickly  increases  the  amount  of  muscular  work  that 
can  be  performed.  (6)  The  total  amount  of  work  that  can  be 
obtained  from  a  muscle  is  greater  with  small  than  with  large  loads, 
since  fatigue  sets  in  more  rapidly  with  the  larger  loads.  (7) 
Marked  activity  in  one  set  of  muscles — the  use  of  the  leg  muscles 
in  long  walks,  for  example — will  diminish  the  amount  of  work 
obtainable  from  other  muscles,  such  as  those  of  the  arm.  It  is 
very  evident  that  the  instrument  may  be  used  to  advantage  in  the 
investigation  of  many  problems  connected  with  gymnastics,  diet- 
etics, stimulants,*  medicines,  etc. 

A  point  of  general  physiological  interest  that  has  been  brought  out  in  con- 
nection with  the  use  of  the  ergograph  calls  for  a  few  words  of  special  mention. 
Mosso  found  that  if  a  muscle — e.  g.,  the  flexor  digitorum  sublimis — is  stimu- 
lated directly  by  the  electrical  current  and  its  contractions  are  recorded  by. 
the  ergograph,  it  will  give  a  curve  similar  to  that  figured  above  for  the  volun- 
tary contractions,  except  that  the  contractions  are  not  so  extensive.  Under 
these  conditions  the  muscle,  when  completely  fatigued  to  electrical  stimula- 
tion, will  respond  to  voluntary  stimulation  from  the  nerve  centers.  On  the 
other  hand,  after  fatigue  from  a  series  of  voluntary  contractions  it  has  been 
observed  that  the  muscle  will  still  give  contractions  if  stimulated  directly  by 
electricity.  It  is  stated,  in  fact,  that  one  can  alternate  a  number  of  times  from 
voluntary  to  electrical  stimulation,  the  fatigue  induced  by  one  method  giving 
place  to  a  series  of  contractions  when  the  other  method  of  stimulating  the 
muscle  is  employed.  It  follows  from  these  facts  that  the  fatigue,  as  observed 
in  voluntary  contractions,  is  not  a  fatigue  of  the  muscles  themselves,  but 
rather  of  some  other  part  of  the  neuromuscular  apparatus.  In  this  apparatus 
we  have  to  consider  a  number  of  elements:  the  cortical  nerve  cells  of  the  cere- 
brum, the  spinal  nerve  cells,  the  synapse  or  synapses  connecting  these  neurons, 

*Schumberg,  "Archiv  f.  physiol.,"   1899,  suppl.  volume,  p.   289,  and 
Palmen,  "  Skandinavisches  Archly  fur  Physiologic,"  1910,  24,  168,  197. 


THE    PHENOMENON    OF    CONTRACTION.  51 

the  motor  end-plates  in  the  muscle,  etc.  The  weak  link  in  this  chain,  the  ele- 
ment that  first  exhibits  fatigue  in  voluntary  movements,  has  not  been  precisely 
determined. 

Sense  of  Fatigue. — It  should  be  noted  in  passing  that  in  con- 
tinued voluntary  contractions  we  are  conscious  of  a  sense  of  fatigue 
which  eventually  leads  us,  if  possible,  to  discontinue  our  eflorts. 
This  sensation  must  arise  from  a  stimulation  of  sensory  nerve  fibers 
within  the  muscle  or  its  tendons,  and  it  may  be  regarded  as  an 
important  regulation  whereby  we  are  prevented  from  pushing  our 
muscular  exertions  to  the  point  of  "  straining." 

Muscle  Tonus, — In  addition  to  the  conditions  of  contraction 
and  of  relaxation  the  living.,  muscle  exhibits  the  phenomenon  of 
"tone."  By  muscle  tone  we  mean  a  state  of  continuous  shortening 
or  contraction  which  under  normal  conditions  is  slight  in  extent 
and  varies  from  time  to  time.  This  condition  is  dependent  upon 
the  connection  of  the  muscle  with  the  nerve  centers,  and  we 
may  assume  that  under  normal  circumstances  the  motor  centers 
are  continually  discharging  subminimal  nerve  impulses  into  the 
muscles  which  cause  chemical  changes  similar  in  kind  to  those 
set  up  by  an  ordinary  voluntary  effort  but  less  in  amount,  the 
result  being  that  the  muscles  enter  into  a  state  of  contraction 
which,  while  slight  in  extent,  is  more  or  less  continuous.  Ac- 
cording to  this  view,  the  whole  neuromuscular  apparatus  is 
in  a  condition  of  tonic  activity,  and  this  state  may  be  referred 
in  the  long  run  to  the  continual  inflow  of  sensory  impulses  into 
the  central  nervous  system.  That  is,  the  tonus  of  the  skeletal 
muscles  is  not  only  dependent  on  the  nerve  centers  (neurogenic), 
but  is  in  reality  an  example  of  reflex  stimulation  of  these  centers. 
The  tone  of  any  particular  muscle  or  group  of  muscles  may  be 
destroyed,  therefore,  by  cutting  its  motor  nerve,  or  less  completely 
by  severing  the  sensory  paths  from  the  same  region.  Several 
authors  (Boeke,  de  Boer*)  have  claimed  that  in  the  reflex  tonus  of 
muscle  the  efferent  path  is  through  the  thoracic  autonomic  system 
rather  than  through  the  cerebrospinal  nerves.  Some  anatomical 
evidence  has  been  collected  to  show  that  skeletal  muscle  does,  in 
fact,  receive  a  double  motor  innervation,  a  direct  innervation 
through  the  motor  fibers  of  the  cranial  or  spinal  nerves,  and  an 
indirect  one  through  autonomic  nerves.  Section  of  these  latter 
in  the  rami  communicantes  is  said  to  destroy  tonus  in  the  muscles 
involved,  and  it  is  suggested  that  reflex  tonus  is  mediated  through 
these  fibers  just  as  reflex  contractions  are  mediated  through  the 
medullated  motor  fibers  of  the  cranial  or  spinal  nerves.  The 
underlying  cause  of  tone  is  poorly  understood.  It  may  be  simply 
a  condition  of  subdued  tetanus  due  to  a  constantly  acting  series  of 
*  de  Boer,  "Zeitschrift  fur  Biologic,"  1915,  65,  239. 


52          THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE. 

sub-minimal  stimuli,  or  it  may  be  an  order  of  contraction  quite 
different  from  the  usual  visible  movements;  that  is  to  say,  the 
shortening  in  the  case  of  tonus  may  be  due  to  a  substance  or  mech- 
anism in  the  muscle -fibers  different  from  that  which  subserves  the 
ordinary  quick  movements  which  we  designate  as  contractions. 
One  observer,  Bottazzi,  for  example,  has  attempted  to  show  that 
tonus  contractions  are  referable  to  changes  in  the  sarcoplasm  of 
the  fiber,  whereas  the  ordinary  contraction  or  twitch  is  effected 
through  the  striated  fibrillse.  However  this  may  be,  the  fact  of 
muscle  tone  is  important  in  a  number  of  ways.  It  is  of  value, 
without  doubt,  for  the  normal  nutrition  of  the  muscle,  and,  as  is 
explained  in  the  chapter  on  Animal  Heat,  it  plays  a  very  important 
part  in  controlling  the  production  of  heat  in  the  body.  The  extent 
of  muscle  tone  varies  with  many  conditions,  the  most  important  of 
which,  perhaps,  are  external  temperature  and  mental  activity. 
With  regard  to  the  first,  it  is  known  that,  as  the  external  tempera- 
ture falls  and  the  skin  becomes  chilled,  the  sensory  stimulation  thus 
produced  acts  upon  the  nerve  centers  and  leads  to  an  increased 
discharge  along  the  motor  paths  to  the  muscle.  The  tone  of  the 
muscles  increases  and  may  pass  into  the  visible  movements  of 
shivering.  By  this  means  the  production  of  heat  within  the  body 
is  increased  automatically.  Similarly,  an  increase  in  mental 
activity,  so-called  mental  concentration,  whether  of  an  emotional 
or  an  intellectual  kind,  leads,  by  its  effect  on  the  spinal  motor 
centers,  to  a  state  of  greater  muscle  tonus,  the  increased  muscular 
tension  being,  indeed,  visible  to  our  eyes. 

The  Condition  of  Rigor. — When  the  muscle  substance  dies 
it  becomes  rigid,  or  goes  into  a  condition  of  rigor:  it  passes  from 
a  viscous  to  a  solid  state.  The  rigor  that  appears  in  the  muscles 
after  somatic  death  is  designated  usually  as  rigor  mortis,  and  its  oc- 
currence explains  the  death  stiffening  in  the  cadaver.  It  is  charac- 
terized by  several  features:  the  muscles  become  rigid,  they  shorten, 
they  develop  an  acid  reaction,  and  they  lose  their  irritability  to 
stimuli.  Whether  all  of  these  features  are  necessary  parts  of  the 
condition  of  rigor  mortis  it  is  difficult  to  say;  the  matter  will  be 
discussed  briefly  below.  Some  of  the  facts  which  have  been  ob- 
served regarding  rigor  mortis  are  as  follows :  After  the  death  of  an 
individual  the  muscles  enter  into  rigor  mortis  at  different  times. 
Usually  there  is  a  certain  sequence,  the  order  given  being  the  jaws 
neck,  trunk,  upper  limbs,  lower  limbs,  the  rigor  taking,  therefore,  a 
descending  course.  The  actual  time  of  the  appearance  of  the  rigidity 
varies  greatly,  however;  it  may  come  on  within  a  few  minutes  or  a 
number  of  hours  may  elapse  before  it  can  be  detected,  the  chief  de- 
termining factor  in  this  respect  being  the  condition  of  the  muscle 
itself.  Death  after  great  muscular  exertion,  as  in  the  case  of  hunted 


THE    PHENOMENON    OF    CONTRACTION.  53 

animals  or  soldiers  killed  in  battle,  is  usually  followed  quickly  by 
muscle  rigor;  indeed,  in  extreme  cases  it  may  develop  almost  imme- 
diately. Death  after  wasting  diseases  is  also  followed  by  an  early 
rigor,  which  in  this  case  is  of  a  more  feeble  character  and  shorter 
duration.  The  development  of  rigor  is  very  much  hastened  by  many 
drugs  that  bring  about  the  rapid  death  of  the  muscle  substance,  such 
as  veratrin,  hydrocyanic  acid,  caffein,  and  chloroform.  A  frog's  mus- 
cle exposed  to  chloroform  vapor  goes  into  rigor  at  once  and  shortens 
to  a  remarkable  extent.  Rigor  is  said  also  to  occur  more  rapidly 
in  a  muscle  still  connected  with  the  central  nervous  system  than 
In  one  whose  motor  nerve 'has  been  severed.  After  a  certain 
interval,  which  also  varies  greatly, — from  one  to  six  days  in  human 
beings, — the  rigidity  passes  off,  the  muscles  again  become  soft  and 
flexible;  this  phenomenon  is  known  as  the  release  from  rigor.  In 
the  cold-blooded  animals  the  development  of  rigor  is  very  much 
slower  than  in  warm-blooded  animals.  Upon  an  isolated  frog's 
muscle  the  most  striking  fact  regarding  rigor  mortis  is  the  shortening 


Fig.  25. — Curve  of  normal  rigor  mortis,  gastrocnemius  muscle  of  frog.  The  curve 
was  obtained  upon  a  kymographion  making  one  revolution  in  eight  days.  The  marks  on 
the  line  below  the  curve  indicate  intervals  of  six  hours.  It  will  be  seen  that  the  shortening 
required  eighteen  hours,  the  relaxation  about  seventy-two  hours. 

that  the  muscle  undergoes.  This  shortening  or  contraction  comes 
on  slowly,  as  is  shown  in  the  accompanying  figure,  but  in  extent 
it  exceeds  the  simple  contraction  obtainable  from  the  living  muscle 
by  means  of  a  maximal  stimulus.  This  part  of  the  phenomenon 
is,  however,  much  less  marked  apparently  in  mammalian  muscle. 
With  regard  to  the  specific  cause  of  the  contraction  of  death  rigor 
the  most  significant  fact  is  the  discovery  made  by  Fletcher  and 
Hopkins,*  that  when  an  excised  muscle  is  kept  well  supplied  with 
oxygen  it  dies  without  giving  a  rigor  contraction.  The  presence  of 
oxygen  ensures  the  oxidation  of  the  lactic  acid  and  thus  prevents  its 
accumulation  in  the  dying  muscle.  We  may  infer  on  the  basis  of 
this  result  that  the  contraction  in  death  rigor  is  due  to  the  accumu- 
*  Fletcher  and  Hopkins,  "Journal  of  Physiology,"  1907,  35,  247. 


54          THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE. 

lation  of  lactic  acid,  that  it  is,  so  to  speak,  a  last  tonic  contraction, 
the  acid  bringing;  into  action  the  mechanism  of  shortening  as  it  does 
in  a  normal  contraction  (p.  73).  In  addition  to  the  rigor  mortis 
that  occurs  after  death  at  ordinary  temperatures,  a  condition  of 
rigor  may  be  induced  rapidly  by  raising  the  temperature  of  the 
muscle  to  a  certain  point.  Rigor  induced  in  this  way  is  designated 
as  heat  rigor  or  rigor  caloris.  Much  uncertainty  has  prevailed  as  to 
whether  heat  rigor  is  different  essentially  from  death  rigor.  Ac- 
cording to  some  physiologists,  the  processes  may  be  regarded  as  the ' 
same,  the  heat  rigor  being  simply  a  death  rigor  that  is  rapidly  devel- 
oped by  the  high  temperature,  this  latter  condition  accelerating 
the  chemical  changes  leading  to  rigor,  as  is  the  case,  for  instance, 
in  the  action  of  chloroform.  This  view  is  supported  by  a  study 
of  the  chemical  changes  that  take  place  under  the  two  condi- 
tions, as  will  be  described  later,  and  by  the  fact  that  some  of 
the  conditions  that  influence  one  phenomenon  have  a  parallel 
effect  upon  the  other.  For  instance,  death  rigor  is  acceler- 
ated by  previous  use  of  the  muscle,  and  the  same  is  true  for  heat 
rigor.  While  a  resting  frog's  muscle  begins  to  go  into  heat  rigor, 
as  judged  by  the  shortening,  at  37°  to  40°  C.;  a  muscle  that  has 
been  greatly  fatigued  shows  the  same  phenomenon  at  25°  to 
27°  C.*  According  to  other  observers,  heat  rigor  is  due  to  an 
ordinary  heat  coagulation  of  the  proteins  present  in  the  muscle 
fiber,  and  it  has  been  claimed  that  a  separate  contraction  may 
be  obtained  on  heating  for  each  of  the  proteins  said  to  exist  in 
the  muscle  fiber,  f  More  recent  observations  J  seem  to  show 
that  when  a  frog's  muscle  is  gradually  heated,  only  two  really 
distinct  contractions  are  obtained,  one  at  39°  C.  (38°  to  40°) 
or  slightly  lower,  and  one  at  50°  C.  (49°  to  51°).  Mammalian 
muscle  gives  also  two  contractions  when  heated,  one  at  47°  C. 
(46°  to  50°)  and  one  at  62°  C.  (61°  to  64°).  In  each  of  these 
cases  the  second  contraction  is  due  to  the  action  of  heat  on  the 
connective-tissue  elements  of  the  muscle.  The  first  contraction  is, 
therefore,  the  one  that  is  characteristic  of  the  muscular  substance 
proper  and  the  one  that  marks  the  occurrence  of  heat  rigor. 
At  the  tempertures  stated,  39°  C.  for  frog's  muscle  and  47°  C. 
for  mammalian  muscle,  the  viscous  material  within  the  sarco- 
lemma  coagulates.  It  does  not  follow  necessarily  that  this  coagula- 
tion is  the  direct  cause  of  the  shortening.  Meigs§  states  that 
plain  muscle  heated  to  50°  C.  lengthens  instead  of  shortening, 


1899  191,  p.  127;  also  Inagaki,  "Zeitschrift  f.  Biol.,"' "  "   ~~~  * 

Vrooman,  "  Bio-chemical  Journal,"  1907,  2,  363. 

Meigs,  "American  Journal  of  Physiology,"  24,  1  and  178,  1909. 


THE    PHENOMENON    OF    CONTRACTION.  55 

although  at  that  temperature  much  of  its  contained  protein  is 
coagulated.  In  striated  muscle,  on  the  other  hand,  coagulation 
may  be  produced  by  alcohol  without  any  noticeable  shortening. 
It  may  be,  therefore,  that  coagulation  and  shortening  are  separate 
results  following  upon  the  chemical  changes  preceding  the  death 
of  the  muscle  substance.  The  coagulation  produced  in  heat  rigor 
is  apparently  more  complete  and  resistant  than  that  of  death  rigor, 
for  ordinary  death  rigor  passes  off  after  a  certain  interval,  even  if 
putrefactive  processes  are  excluded;  the  rigor  from  heat  or  from 
chloroform,  on  the  contrary,  shows  no  release. 

PLAIN   OR  SMOOTH    MUSCULAR   TISSUE. 

Occurrence  and  Innervation. — Plain  or  long  striated  muscular 
tissue  occurs  in  the  walls  of  all  the  so-called  hollow  viscera  of  the 
body,  such  as  the  arteries  and  veins,  the  alimentary  canal,  the 
genital  and  urinary  organs,  the  bronchi,  etc.,  and  in  other  special 
localities,  such  as  the  intrinsic  muscles  of  the  eyeball,  the  muscles 
attached  to  the  hair  follicles,  etc.  In  structure  it  differs  funda- 
mentally from  cross-striated  muscle,  in  that  it  occurs  in  the  form 
of  relatively  minute  cells,  each  with  a  single  nucleus,  which  are 
united  to  form,  in  most  cases,  muscular  membranes  constituting 
a  part  of  the  walls  of  the  hollow  viscera.  Each  muscle-cell  is 
spindle  shaped,  contains  a  single  ekmgated  nucleus,  and  the  cyto- 
plasm is  traversed  by  fine  fibrils  (myofibrillse)  which  are  said  to 
continue  from  one  cell  to  another.  As  in  the  case  of  the  striated 
muscle,  these  fibrils  are  supposed  to  constitute  the  contractile 
element.  The  muscle-cells  are  supplied  with  nerve-fibers  belong- 
ing to  the  autonomic  system  (p.  251),  which  originate  directly  from 
so-called  sympathetic  nerve-cells,  and  only  indirectly,  therefore, 
from  the  central  nervous  system. 

Speaking  generally,  the  contractions  of  this  tissue  are  removed 
from  the  direct  control  of  the  will,  being  regulated  by  reflex  and 
usually  unconscious  stimulations  from  the  central  nervous  system. 
All  the  important  movements  of  the  internal  organs,  or,  as  they 
are  sometimes  called,  the  organs  of  vegetative  life,  are  effected 
through  the  activity  of  this  contractile  tissue.  From  this  stand- 
point their  function  may  be  regarded  as  more  important  than  that 
of  the  mass  of  the  voluntary  musculature,  since  so  far  as  the  mere 
maintenance  of  the  life  of  the  organism  is  concerned,  the  proper 
action  and  co-ordination  of  the  movements  of  the  visceral  organs 
is  at  all  times  essential. 

Distinctive  Properties. — The  phenomena  of  contraction  shown 
by  plain  muscles  are,  in  general,  closely  similar  to  those  already 
studied  for  striated  muscle,  the  one  great  difference  being  the 
much  greater  sluggishness  of  the  changes.  Plain  muscles  differ 


56         THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE. 

among  themselves,  of  course,  as  do  the  striated  muscles,  but,  speak- 
ing generally,  the  simple  contractions  of  plain  muscle  have  a  very 
long  latent  period  that  may  be  a  hundred  or  five  hundred  times 
as  long  as  that  of  cross-striated  muscle,  and  the  phases  of  shortening 
and  of  relaxation  are  also  similarly  prolonged;  so  that  the  whole 
movement  of  contraction  is  relatively  slow  and  gentle  (see  Fig. 
26).  Plain  muscle  responds  to  artificial  stimuli,  but  the  electrical 
current  is  obviously  a  less  adequate — that  is,  a  less  normal — stimulus 
for  this  tissue  than  for  the  striped  muscle.  The  amount  of  current 
necessary  to  make  it  contract  is  far  greater.  The  amount  of  con- 
traction varies  with  the  strength  of  stimulus, — that  is,  the  tissue 
gives  submaximal  and  maximal  contractions.  Two  successive 
stimuli  properly  spaced  will  cause  a  larger  or  summated  contraction, 
and  a  series  of  stimuli  will  give  a  fused  or  tetanic  contraction.  The 
rate  of  stimulation  necessary  to  produce  tetanus  is,  of  course,  much 
slower  than  for  cross-striped  muscle.  The  stomach  muscle  of  the 
frog,  for  instance,  requires  only  one  stimulus  at  each  five  sec- 


Fig.  26.-7-Curve  of  simple  contraction  of  plain  muscle.     The  middle  line  is  the  time 
record,  marking  intervals  of  a  second.     The  lowermost  line  indicates  at  the    break  the  mo- 
ment of  stimulation  (short-lasting,  tetanizing  current).    It  will  be  seen  that  the  latent  period 
between  beginning  of  stimulation  and  beginning  of  contraction  is  equal  to   about  three  • 
seconds. 

onds  to  cause  tetanus.*  A  distinguishing  and  important  charac- 
teristic of  the  plain  muscle  is  its  power  to  remain  in  tone, — that 
is,  to  remain  for  long  periods  in  a  condition  of  greater  or  less  con- 
traction. Doubtless  this  tonic  contraction  under  normal  relations 
is  usually  dependent  upon  stimulation  received  through  the  ner- 
vous system  (neurogenic  tonus),  but  the  muscle,  when  completely 
isolated  from  the  central  nervous  system,  whether  in  or  out  of 
the  body,  continues  to  exhibit  the  phenomenon  of  tone  to  a 
remarkable  degree.  In  most  of  the  organs  in  which  plain  muscle 


THE    PHENOMENON    OF    CONTRACTION.  57 

occurs  there  are  present  also  numerous  nerve  cells,  and  it  is 
therefore  still  a  question  as  to  whether  the  tonic  changes  shown 
by  this  tissue,  after  separation  of  its  extrinsic  nerves,  depend 
upon  a  property  of  the  muscle  itself  (myogenic  tonus)  or  upon 
their  intrinsic  nerve  cells.  Most  observers  adopt  the  former 
view.  The  importance  of  this  property  of  tone  in  the  plain 
muscle  tissues  will  be  made  fully  apparent  in  the  description 
of  the  physiology  of  the  organs  of  circulation  and  digestion. 
We  shall  find  that  constantly  throughout  life  the  walls  of  the  small 
arteries  resist  a  high  internal  pressure,  and  that  in  other  visceral 
organs  pressures  of  varying  amounts  are  supported  by  the  tonicity 
of  the  plain  muscle  in  their  walls.  Many  interesting  observations 
in  late  years  tend  to  show  that  the  tension  developed  in  plain  muscle 
in  a  state  of  tone  is  accompanied  by  little  or  no  production  of  heat 
and  by  little  evidence  of  chemical  changes  of  an  oxidative  nature.* 
In  some  very  economical  way,  so  far  as  the  consumption  of  mate- 
rial and  energy  is  concerned,  the  condition  of  the  muscle  may  be 
changed  from  a  state  of  little  tone  to  one  of  greater  tone.  Plain 
muscle  may  exhibit  also  the  phenomenon  of  rhythmical  activ- 
ity— that  is,  under  proper  conditions  it  may  contract  and  re- 
lax rhythmically  like  heart  tissue,  "f  Such  movements  have 
been  observed  and  studied  upon  the  plain  muscle  of  the  ureter, 
the  bladder,  the  esophagus,  stomach,  and  other  portions  of  the 
alimentary  canal,  the  spleen,  the  blood-vessels,  etc.  This  property 
seems  to  be  very  unequally  distributed  among  the  different  kinds 
of  plain  muscle  found  in  the  same  or  different  animals,  but  this 
fact  serves  only  to  illustrate  the  point  already  sufficiently  empha- 
sized, that  grouping  one  kind  of  tissue — e.  g.,  plain  muscle — into 
a  common  class  does  not  signify  that  the  properties  of  all  the  mem- 
bers of  the  group  are  identical.  The  question  as  to  how  far  the  phe- 
nomenon of  rhythmical  contraction  is  entirely  muscular  and  how  far 
it  depends  upon  intrinsic  nerve  cells  is  a  complex  one;  the  answer 
will  probably  vary  for  different  organs,  and  the  subject  will  therefore 
be  considered  in  the  organs  as  they  are  treated. 

Cardiac  Muscular  Tissue. — As  the  muscle  cells  of  cardiac 
tissue  are  somewhat  intermediate  in  structure  between  the  striated 
fibers  of  voluntary  muscle  and  the  cells  of  plain  muscles,  so  their 
physiological  properties  to  some  extent  stand  between  these  two 
extremes.  The  rate  of  contraction,  for  instance,  while  slower  than 
that  of  the  fibers  of  skeletal  muscles,  is  more  rapid  than  that  of 
plain  muscle.  The  most  striking  peculiarity  of  heart  muscle  is, 
however,  its  power  of  rhythmical  contractility,  and  this,  as  well  as 

*  Snyder,  "  American  Journal  of  Physiology,"  35,  340,  1914. 
t  Engelmann,  "Archiv  f .  d.  ges.  Physiologic/'  2,  243,  1869.    Stiles,  "  Amer. 
Jour,  of  Physiology,"  5,  338,  1901. 


58  THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 

its  other  properties,  is  so  directly  concerned  with  its  functions  as 
an  organ  of  circulation  that  it  may  be  discussed  more  profitably 
in  that  connection. 

Ciliated  Cells. — In  the  mammalian  body  the  phenomenon  of 
contractility  is  exhibited  not  only  by  the  well-defined  muscular 
tissue,  but  also  by  the  leucocytes  and  especially  by  the  cilia  of  the 
ciliated  epithelium.  Epithelial  cells  with  motile  cilia  are  found  lin- 
ing the  mucous  membrane  of  the  air-passages  in  the  trachea,  larynx, 
bronchi,  and  nose,  in  the  lacrimal  duct  and  sac,  in  the  genital  pas- 
sages, uterus  and  Fallopian  tubes  and  the  tubules  of  the  epididymis, 
and  in  the  Eustachian  tube  and  part  of  the  middle  ear.  Similar 
cells  are  found  lining  the  ventricles  of  the  brain  and  the  central 
canal  of  the  cord.  The  cilia  in  this  latter  position  have  been 
demonstrated  to  be  motile  in  the  frog,  and  according  to  an  old 
observation  by  Purkinje*  the  same  is  true  for  the  mammalian 
(sheep)  embryo.  So  also  in  the  neck  of  the  uriniferous  tubule 
ciliated  cells  are  said  to  occur,  but  whether  they  are  motile  or  not  has 
not  been  demonstrated.  In  the  internal  ear  and  the  olfactory  mucous 
membrane  the  so-called  sense  cells  are  also  ciliated,  but  here  at  least 
the  cilia  are  probably  not  motile.  Ordinarily  each  ciliated  epithelial 
cell  carries  a  bunch  of  cilia,  all  of  which  contract  together,  but 
motile  protoplasmic  prolongations  of  the  cell  may  occur  singly,  as 
is  illustrated  in  the  spermatozoa,  for  instance,  and  in  many  of  the 
protozoa  and  plant  cells.  In  the  lower  forms  of  life  cilia  play 
obviously  a  very  important  role  in  locomotion,  the  capture  of  food, 
and  respiration,  and  their  form  and  manner  of  movement  vary 
greatly.  The  form  of  movement  or  manner  of  contraction  was 
formerly  described  under  four  heads, — the  hook  form,  the  pendular, 
the  undulatory  or  wave-like,  and  the  funnel  form  or  infundibulary. 
With  the  exception  of  the  spermatozoa,  the  cilia  found  in  mam- 
mals show  the  first  form  of  contraction.  The  little  processes  are 
contracted  quickly  in  one  direction,  so  as  to  take  a  hook  shape, 
and  then  relax  more  slowly,  the  relaxation  taking  several  times 
as  long  as  the  contraction.  The  whole  movement  is  rhythmical  and 
very  rapid.  The  cilia  of  the  epithelium  of  the  frog's  pharynx  and 
esophagus,  which  have  been  the  most  frequently  studied  in  the 
higher  animals,  contract,  according  to  Engelmann,  at  the  rate 
of  12  times  per  second.  When  a  field  of  epithelium  is  observed 
under  the  microscope  the  contractions  pass  over  it  in  a  definite 
direction,  but  so  rapidly  that  the  eye  is  not  able  to  analyze  them; 
one  obtains  the  impression  simply  of  a  swiftly  flowing  current. 
As  the  cilia  begin  to  die,  their  movements  become  less  rapid,  and 
the  nature  of  the  contractions  and  their  progress  from  cell  to  cell 
can  be  satisfactorily  observed.  In  the  mammalia  the  function  of 
*  Purkinje,  "  Miiller's  Archiv,"  1836. 


THE    PHENOMENON    OF    CONTRACTION.  59 

the  ciliated  epithelium  is  supposed  to  be  entirely  mechanical, — 
that  is,  the  cilia  move  substances  lying  upon  them.  In  the  ovi- 
ducts they  move  or  help  to  move  the  ovum  toward  the  uterus, 
and'  in  this  latter  organ  their  motion  is  supposed  to  guide  the 
spermatozoa  from  the  uterus  toward  the  oviducts, — that  is, 
the  resistance  offered  to  the  motile  spermatozoa  guides  their  move- 
ments. So  in  the  respiratory  passages  foreign  particles  of  various 
sorts,  together  with  the  secretion  of  the  mucous  glands,  are  moved 
toward  the  mouth,  the  effect  being  to  protect  the  air-passages 
from  obstruction.  The  contraction  and  relaxation  of  the  cilia  are 
assumed  to  be  phenomena  of  essentially  the  same  order  as  those 
exhibited  by  the  muscle  tissue.  A  theory  that  will  adequately 
explain  one  will  doubtless  be  applicable  to  the  other.  Many 
interesting  facts  have  been  established  regarding  ciliary  move- 
ments. The  contractions  of  the  cilia  in  any  given  field — the 
trachea,  for  instance — follow  in  a  definite  sequence  and  are  co- 
ordinated. The  waves  of  contraction  progress  in  a  definite  direction. 
This  fact  increases  greatly  the  effectiveness  of  the  cilia  in  per- 
forming work.  Thus,  in  spite  of  their  extremely  minute  size,  it 
is  estimated  that  an  area  of  a  square  centimeter  is  capable  of 
moving  a  load  of  336  gms.  The  contractions  are  automatic, — 
that  is,  the  stimulus  causing  them  is  not  dependent  upon  a  con- 
nection with  the  nervous  system,  but  upon  processes  arising  within 
the  cell  itself;  the  cilia  of  a  single  completely  isolated  cell  may 
continue  to  contract  vigorously.  The  movement  may  continue 
for  several  days  after  the  death  of  the  individual,  thus  again  showing 
the  physiological  independence  of  the  structure.  The  ciliated  cells 
may  conduct  a  stimulus  or  impulse  to  other  cells  even  after  its 
own  cilia  have  lost  their  contractility.  This  fact  is  particularly 
significant  in  general  physiology,  as  it  aids  in  showing  that  the 
property  of  conductivity  which  is  exhibited  in  such  high  degree 
by  nerve  fibers  is  possessed  to  a  lower  degree  by  other  tissues. 
The  ciliary  movement  is  affected  by  variations  in  temperature,  and 
if  the  temperature  passes  beyond  an  optimum  point  the  cilia  fall 
into  a  condition  resembling  heat  rigor  in  the  muscle.  Their  move- 
ments are  affected  also  by  the  reaction  of  the  medium,  being  at 
first  accelerated  and  then  slowed  or  destroyed  by  a  slight  degree 
of  acidity  and  favored  by  a  very  slight  degree  of  alkalinity.* 


"Dictionnaire  de  Physiologic,"  vol.  Ui,  1898. 


CHAPTER  II. 

THE  CHEMICAL  COMPOSITION  OF  MUSCLE  AND  THE 

CHEMICAL  CHANGES  OF  CONTRACTION  AND 

OF  RIGOR  MORTIS. 

Muscle  Plasma. — The  beginning  of  our  present  knowledge  of 
the  chemical  composition  of  muscle  is  found  in  some  interesting  ex- 
periments made  by  Kiihne  upon  frog's  muscle.  Kiihne  froze  the 
living  muscle  to  a  hard  mass,  cut  it  into  fine  shavings  with  cold 
knives,  and  ground  the  pieces  thoroughly  in  a  cold  mortar.  The 
fine  muscle  snow  thus  obtained  was  pu*  under  high  pressure  and 
a  liquid  expressed  which  was  assumed  to  represent  the  fluid  living 
substance  in  the  normal  fiber.  This  muscle  plasma  clotted  on  stand- 
ing, much  as  blood  does,  the  muscle  clot  shrinking  and  squeezing 
out  a  muscle  serum.  Similar  experiments  have  since  been  per- 
formed by  Halliburton*  on  mammalian  muscle. 

Composition  of  the  Muscle  Plasma. — Using  the  term  muscle 
plasma  to  designate  the  entire  contents  of  the  muscle  fiber  within 
the  sarcolemma,  it  is  obvious  that  this  material  should  contain  all 
the  constituents  that  properly  belong  to  the  muscle,  in  contradis- 
tinction to  the  substances  found  in  the  connective  tissue  binding 
the  muscle  fibers  together. 

The  constituents  in  addition  to  water  that  are  known  to  occur 
in  muscle  are  very  numerous  indeed,  and  difficult  to  classify.  They 
may  be  grouped  under  the  following  heads:  (1)  Proteins.  (2)  Car- 
bohydrates and  fats.  (3)  Nitrogenous  extractives  (creatin,  urea, 
etc.).  (4)  Non-nitrogenous  extractives  (lactic  acid,  inosite,  etc.). 
(5)  Pigments.  (6)  Ferments.  (7)  Inorganic  salts.  Very  little 
that  is  positive  can  be  stated  regarding  the  physiological  role 
of  most  of  these  constituents,  the  interest  that  attaches  to  them 
at  present  being  largely  on  the  chemical  side. 

The  Muscle  Proteins,  f — The  proteins  of  the  muscle  have  been 
investigated  by  a  number  of  observers,  but  unfortunately  the 
terminology  employed  has  not  been  uniform,  and  the  facts  so  far 

*  Halliburton,  "Journal  of  Physiology,"  8,  133,  1888. 

t  Von  Fiirth,  "Archiv  f.  exper.  Path.  u.  Pharmakol.,"  36,  231,  1895,  and 
"Handbuch  der  Biochemie,"  1909,  vol.  2,  p.  244;  Halliburton,  "Journal  of 
Physiology,"  8,  133,  1888;  Stewart  and  Sollman,  ibid.,  24,  427,  1899. 

60 


THE    CHEMISTRY    OF    MUSCLE.  61 

as  they  are  known  to  us  seem  to  be  obviously  incomplete.  Ac- 
cording to  von  Fiirth,  two  proteins  may  be  obtained  from  mam- 
malian muscle  by  extracting  it  with  dilute  saline  solutions, — namely, 
myosin  and  myogen,  the  latter  existing  to  three  or  four  times  the 
amount  of  the  former.  Myosin  belongs  to  the  globulin  group  of 
proteins  (see  appendix) ;  it  is  coagulated  by  heat  at  44°  to  50°  C., 
it  is  precipitated  by  dialysis  or  by  weak  acids,  it  is  easily  precipi- 
tated from  its  solutions  by  adding  an  excess  of  neutral  salts,  such 
as  sodium  chlorid,  magnesium  or  ammonium  sulphate.  With 
the  last  salt  it  is  completely  precipitated  when  the  salt  is  added 
to  one-half  saturation  or  less.'  Its  most  interesting  property,  how- 
ever, is  that  on  standing  at  ordinary  temperatures  it  passes  over 
into  an  insoluble  modification  which  separates  out  as  a  sort  of 
clot.  Following  the  terminology  used  for  the  blood,  this  insoluble 
modification  is  called  myosin  fibrin.  Myogen,  the  other  protein, 
seems  to  fall  into  the  group  of  albumins  rather  than  globulins. 
It  is  not  precipitated  by  dialysis  and  requires  more  than  half 
saturation  with  ammonium  sulphate  for  its  complete  precipitation. 
It  is  coagulated  by  heat  at  a  temperature  of  55°  to  65°  C.  Solutions 
of  myogen  on  standing  also  undergo  a  species  of  clotting,  the  in- 
soluble protein  that  is  formed  in  this  case  being  called  myogen  fibrin. 
It  appears,  however,  that  in  changing  to  myogen  fibrin  the  myogen 
passes  through  an  intermediate  stage,  designated  as  soluble  myogen 
fibrin,  in  which  its  temperature  of  heat  coagulation  is  as  low  as 
30°  to  40°  C., — the  lowest  temperature  recorded  for  any  protein. 
As  was  stated  in  the  paragraph  on  muscle  rigor,  it  is  known  that 
frog's  muscle  goes  into  heat  rigor  at  about  37°  to  40°  C.,  and  in 
accordance  with  this  fact  it  is  stated  that  a  protein,  soluble  my- 
ogen fibrin,  which  is  not  present  in  mammalian  muscle,  occurs 
normally  in  the  muscle  of  the  frog  and  also  of  the  fishes. 

It  may  be  doubted  whether  these  proteins  exist  as  such  in 
the  living  muscle.  Extracts  must  of  necessity  be  made  after  the 
muscle  plasma  is  dead  and  probably  coagulated.  Myogen  is  said 
not  to  occur  in  the  muscles  of  the  invertebrates.  It  should 
be  added  that  after  the  most  complete  extraction  with  saline 
solutions  the  muscle  fiber  still  retains  much  protein  material, 
and  its  structural  appearance,  so  far  as  cross-striation  is  con- 
cerned, remains  unaltered.  The  portion  of  protein  material 
thus  left  in  the  muscle  fiber  as  a  sort  of  skeleton  framework 
is  designated  as  the  muscle  stroma;  it  is  not  soluble  in  solu- 
tions of  neutral  salts,  but  dissolves  readily  in  solutions  of 
dilute  alkalies.  In  striped  muscle  this  so-called  stroma  forms 
about  9  per  cent,  of  the  weight  of  the  muscle;  while  in  the  heart 
muscle  it  makes  about  56  per  cent.,  and  in  the  smooth  muscle, 
72  per  cent.  It  is  at  present  uncertain  whether  the  myosin  and 


62  THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 

myogen  represent  the  protein  constituents  of  the  contractile  ele- 
ments of  the  muscle  fibers  or  of  the  undifferentiated  portion,  the 
sarcoplasm.  The  proteins  of  plain  muscle  tissue  and  of  cardiac 
muscle  have  not  received  so  much  attention  as  those  of  voluntary 
muscle.  It  is  stated,  however,  that  the  proteins  extracted  from 
these  tissues  by  salt  solutions  are  coagulable  on  standing,  as  in 
the  case  of  the  extracts  of  voluntary  muscle.  In  plain  muscle 
two  proteins,  in  addition  to  some  nucleoprotein,  are  described, 
one  belonging  to  the  albumin  and  one  to  the  globulin  class,  but 
the  identity  or  relationship  of  these  proteins  to  those  above  de- 
scribed has  not  been  established.  In  heart  muscle,  myosin  and 
myogen  occur  in  practically  the  same  proportions  as  in  voluntary 
muscle,  but  the  amount  of  stroma  left  undissolved  after  treatment 
with  saline  solutions  is,  as  stated  above,  much  greater  than  in 
skeletal  muscle.* 

The  Carbohydrates  of  Muscle. — Muscle  contains  a  certain 
amount  of  sugar  (dextrose  or  dextrose  and  isomaltose),  and  also 
under  normal  conditions  a  considerable  quantity  of  glycogen,  or 
so-called  animal  starch.  The  formation  and  the  consumption  of 
glycogen  in  the  body  constitute  one  of  the  most  interesting  chapters 
in  the  physiology  of  nutrition,  and  the  relations  of  glycogen  will 
be  treated  more  fully  under  that  head.  It  may  be  stated  here, 
however,  that  the  muscular  tissue  has  the  power  of  converting  the 
sugar  brought  to  it  by  the  blood  into  glycogen.  It  is  a  synthetic 
reaction  in  which  the  simple  molecule  of  the  monosaccharide 
(dextrose)  is  converted  by  dehydration  and  condensation  to  the 
larger  molecule  of  the  polysaccharide  (glycogen).  It  is  repre- 
sented in  principle  by  the  reaction 

n(C6H1206)—  n(H20)  =  (C6H10O5)n. 

The  glycogen  thus  formed  is  stored  in  the  muscle  and  forms 
a  constant  constituent  of  well-nourished  muscle  in  the  resting 
condition,  the  amount  varying  between  0.5  and  0.9  per  cent,  of 
the  weight  of  the  muscle.  The  glycogen  thus  stored  in  the  muscle 
is  consumed  by  the  tissue  during  its  activity,  and  it  is  assumed 
that  before  it  is  thus  consumed  it  is  converted  back  into  sugar  by 
the  action  of  an  amylolytic  enzyme  contained  in  the  muscle.  The 
glycogen,  therefore,  itself  represents  a  local  deposit  of  carbohydrate 
nutritive  material.  The  sugar  and  the  glycogen  must  be  con- 
sidered as  one  from  the  standpoint  of  the  nutrition  of  the  muscle. 
During  muscular  activity  the  store  of  glycogen  is  used  up,  and  if 
the  activity  is  sufficiently  prolonged  it  may  be  made  to  disap- 

*  Vincent  and  Lewis,  "Journal  of  Physiology,"  26,  445,  1901;  also  "Zeit- 
schrift  f.  physiolog.  Chemie,"  34,  417,  1901-2;  Stewart  and  Sollman,  loc.  cit.; 
von  Fiirth,  "General  Review,  Handbuch  der  Biochemie,"  vol.  2,  part  2,  p.  244. 


THE    CHEMISTRY    OF    MUSCLE.  63 

pear  entirely.  Among  the  many  uncertain  and  contradictory 
statements  regarding  the  chemical  changes  in  active  muscle,  this 
fact  stands  out  in  pleasant  contrast  as  one  that  is  satisfactorily 
demonstrated. 

Lactic  Acid  (C3H6O3).  —  Lactic  acid  is  found  in  varying  amounts 
in  the  extracts  of  muscle.  The  acid  that  is  obtained  is  the  so-called 
ethidene  lactic  acid  or  a-hydroxypropionic  acid  (CH;JCHOHCOOH), 
and  differs  from  the  lactic  acid  found  in  sour  milk  in  that  it  ro- 
tates the  plane  of  polarized  light  to  the  right.  The  lactic  acid  in 
sour  milk  is  produced  by  bacterial  fermentation,  and  is  inactive  to 
polarized  light,  because  it  exists  in  racemic  form  ;  that  is,  it  con- 
sists of  equal  amounts  of  the  right-handed  form  which  turns  the 
plane  of  polarization  to  the  right  and  of  the  left-handed  form 
which  turns  it  to  the  left.  In  the  muscle  the  dextro-rotary  form 
is  found  mainly  or  only,  and  this  form,  therefore,  is  frequently 
designated  as  sarcolactic  (or  paralactic)  acid.  Recent  work 
indicates  that  in  the  perfectly  resting  muscle  lactic  acid  is 
present  only  in  traces.  The  amount  is  greatly  increased  during 
contraction  or  in  the  processes  leading  to  rigor.  This  substance 
may  be  considered,  therefore,  as  an  intermediary  product  formed 
in  the  course  of  the  chemical  reactions  constituting  the  normal 
metabolism  of  the  muscle.  Its  origin  is  considered  in  more  detail 
below. 

The  Nitrogenous  Extractives  (Nitrogenous  Wastes).  —  Muscle 
extracts  contain  numerous  crystallizable  nitrogenous  substances 
which  are  regarded  as  the  end-products  of  the  disassimilation 
or  catabolism  of  the  living  protein  material  of  the  muscle.  The 
number  of  these  substances  that  have  been  found  in  traces  or 
weighable  quantities  is  rather  large.  They  have  aroused  great 
interest  because  their  structure  throws  some  light  on  the  nature 
of  protein  catabolism.  The  one  that  occurs  in  largest  amount  is 
creatin,  C4H9N3O2,  or  methyl-guanidin-acetic  acid,  NHCNH2- 
NCH3CH2COOH.  Creatin  is  present  in  amounts  equal  to  0.4 
to  0.5  per  cent,  of  the  weight  of  the  muscle.  The  relations  of  this 
substance  to  the  creatinin  (C4H7N30)  found  in  the  urine  are  dis- 
cussed on  p.  859.  Another  nitrogenous  body  with  basic  proper- 
ties which  occurs  in  amounts  about  equal  to  the  creatin  is  carno- 
sin,  C9Hi4N403.*  It  is  probably  a  derivative  of  histidin,  since 
on  .  hydrolysis  it  yields  histidin  and  alanin  (Gulewitsch)  .  Noth- 
ing is  known  of  its  physiological  significance.  In  addition  there 
is  a  group  of  bodies  supposed  to  represent  the  end-products  of 
the  breaking  up  of  the  nucleins  of  the  muscle,  all  of  which  be- 
long to  the  so-called  purin  bases.  These  are  :  Uric  acid 


Von  Fiirth  and  Schwarz,  "Biochemische  Zeitschrift,"  1911,  30,  413. 


64          THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE. 


xanthin  (CsI^NA),  hypoxanthin  (C5H4N4O),  guanin  (C5H5N5O), 
adenin  (C5H5N5),  and  carnin  (CrHsNiOt)*  They  will  be  re- 
ferred to  more  fully  in  the  section  on  Nutrition.  Several  other 
nitrogenous  extractives  have  been  isolated  and  named,  but  there 
is  perhaps  some  doubt  as  to  their  chemical  individuality.  These 
nitrogenous  products  are  found  in  the  various  meat  extracts  and 
meat  juices  used  in  dietetics.  While  they  possess  no  direct  nutri- 
tive value,  it  seems  probable  (see  chapter  on  Gastric  Digestion) 
that  they  may  have  a  stimulating  action  upon  the  secretion  of  the 
gastric  glands. 

Pigments.  —  The  red  color  of  many  muscles  is  believed  to  be 
due  to  the  presence  of  a  special  pigment  which  resembles  in  its 
structure  and  its  properties  the  hemoglobin  of  the  red  blood 
corpuscles,  and  perhaps  is  identical  with  it.  This  pigment  is  known 
as  myohematin  or  myochrome.  It  belongs  presumably  to  the 
group  of  so-called  respiratory  pigments,  which  have  the  property 
of  holding  oxygen  in  loose  combination,  and  by  virtue  of  this 
property  it  takes  part  in  the  absorption  of  oxygen  by  the  muscular 
tissue. 

Enzymes.  —  Very  active  chemical  changes  take  place  in  muscle 
during  contraction  as  well  as  during  rest.  These  metabolic  changes 
involve  processes  of  hydrolysis,  of  oxidation,  of  reduction,  and  of 
synthesis,  and,  in  most  cases,  they  are  supposed  to  be  effected 
through  the  agency  of  enzymes.  In  accordance  with  this  general 
statement  very  many  different  kinds  of  enzymes  have  been  shown 
to  occur  in  muscular  tissue:  proteolytic,  amylolytic,  and  lipolytic 
enzymes,  oxidases  or  peroxidases,  reductases,  an  enzyme  capable 
of  splitting  off  urea  from  arginin  (arginase),  probably  deaminases 
that  split  off  ammonia  from  the  amino-acids,  etc.  Most  of  these 
enzymes  will  be  referred  to  more  or  less  specifically  in  the  section 
on  Nutrition. 

The  Inorganic  Constituents.  —  Muscle  tissue  contains  a  number 
of  salts,  chiefly  in  the  form  of  the  chlorids,  sulphates,  and  phos- 
phates of  sodium,  potassium,  calcium,  magnesium,  and  iron.  As 
in  other  tissues,  the  potassium  salts  predominate  in  the  tissue 
itself.  In  frog's  muscle  the  entire  ash  constitutes  about  0.88 
per  cent,  of  the  dry  material  of  the  muscle,  and  of  this  ash  the 
potassium  and  the  phosphoric  acid  together  make  up  more 
than  80  per  cent.  (Urano).  These  inorganic  constituents  are 
inost  important  to  the  normal  activity  of  the  muscle,  and, 
indeed,  in  two  ways:  first,  in  that  they  maintain  a  normal 
osmotic  pressure  within  the  substance  of  the  fibers  and  thus 
control  the  exchange  of  water  with  the  surrounding  lymph  and 
blood;  second,  in  that  they  are  necessary  to  the  normal  structure 
and  irritability  of  the  living  muscular  tissue.  Serious  variations 


THE    CHEMISTRY    OF    MUSCLE.  65 

in  the  relative  amounts  of  these  salts  cause  marked  changes  in 
the  properties  of  the  tissues,  as  is  explained  in  the  section  on 
Nutrition,  in  which  the  general  nutritive  importance  of  the  salts 
is  discussed,  and  also  in  the  section  dealing  with  the  cause  of  the 
rhythmical  activity  of  the  heart. 

Chemical  Changes  in  the  Muscle  during  Contraction  and 
Rigor. — The  chemical  changes  known  to  occur  in  muscle  as  a  result 
of  contraction  under  normal  conditions  are  the  following:  (1) 
Production  of  carbon  dioxid.  (2)  Production  of  lactic  acid.  (3) 
Disappearance  of  glycogen.  A  complete  theory  of  contraction 
would  include,  of  course,  ah  explanation  of  the  relation  of  these 
changes  to  one  another  and  to  the  processes  of  contraction  and 
relaxation.  We  do  not  at  present  possess  such  a  theory,  and 
consequently  the  significance  of  the  facts  known  can  only  be 
guessed  at  or  stated  in  a  provisional  way. 

Production  of  Carbon  Dioxid. — After  increased  muscular  ac- 
tivity it  may  be  shown  that  an  animal  gives  off  a  larger  amount 
of  carbon  dioxid  in  its  expired  air.  In  such  cases  the  carbon  dioxid 
produced  in  the  muscles  is  given  off  to  the  blood,  carried  to  the 
lungs,  and  then  exhaled  in  the  expired  air.  Pettenkofer  and  Voit, 
for  instance,  found  that  during  a  day  in  which  much  muscular 
work  was  done  a  man  expired  nearly  twice  as  much  CO2  as  during 
a  resting  day.  The  same  fact  can  be  shown  directly  upon  an  iso- 
lated muscle  of  a  frog  made  to  contract  by  electrical  stimulation. 
The  carbon  dioxid  in  this  case  diffuses  out  of  the  muscle  in  part 
to  the  surrounding  air,  and  in  part  remains  in  solution,  or  in 
chemical  combination  as  carbonates,  in  the  liquids  of  the  tissue. 
It  has  been  shown  by  Hermann*  and  others  that  a  muscle  that  has 
been  tetanized  gives  off  more  carbon  dioxid  than  a  resting  muscle 
when  their  contained  gases  are  extracted  by  a  gas  pump.  This  CC>2 
arises  from  the  oxidation  of  some  of  the  constituents  of  the  muscle, 
and  its  existence  is  an  indication  that  in  their  final  stages  the 
changes  in  the  muscle  are  equivalent  to  those  of  ordinary  combus- 
tion at  high  temperatures,  the  burning  of  wood  or  fats,  for  instance. 
Fletcher  f  has  discovered  the  significant  fact  that  the  increased 
elimination  of  CO2  following  upon  contraction  is  clearly  shown  only 
when  the  muscle  is  well  supplied  with  oxygen.  In  the  absence  of 
oxygen  contraction  may  cause  no  increase  in  the  CO2  given  off. 
This  author  calls  attention  to  the  fact  that  CO2  is  given  off  by  a 
muscle  in  two  ways.  .  In  the  resting  excised  muscle  there  is  a  con- 
stant small  formation  of  C02  which  he  believes  is  due  to  the  action 

*  Hermann,  " Untersuchungen  iiber  den  Stoffwechsel  der  Muskeln,  etc.," 
Berlin,  1867. 

t  Fletcher,  "Journal  of  Physiology,"  1902,  28,  474;  also  Fletcher  and  Hop- 
kins, Croonian  Lecture,  "Proceedings  of  the  Royal  Soc.,"  London,  B.  89,  444, 
1917. 


66  THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 

of  lactic  acid  on  the  fixed  carbonates  in  the  tissues.  This  liberation 
of  CO2  has  no  special  physiological  significance.  On  the  other 
hand,  when  a  muscle  is  made  to  contract  in  air  or  in  oxygen,  there 
is  a  relatively  large  and  sudden  output  of  CO2  which  is  obviously 
dependent  upon  processes  of  oxidation  in  the  muscle  and  is  at- 
tended by  a  parallel  liberation  of  heat.  This  latter  yield  of  CO2 
does  not  take  place  if  the  muscle  is  made  to  contract  under  anaero- 
bic conditions;  that  is  to  say,  in  the  absence  of  oxygen.  It  would 
seem  to  follow  from  this  fact  that  the  contraction  or  shortening  of 
the  muscle  is  what  may  be  called  an  anaerobic  phenomenon,  not 
dependent  upon  oxidative  changes.  An  oxidative  reaction  with  a 
resulting  output  of  CO2  follows  the  contraction  under  normal  con- 
ditions. Its  significance  in  relation  to  the  contraction  will  be  re- 
ferred to  below.  These  facts  seem  to  be  in  accord  with  prevalent 
ideas  regarding  the  nature  of  the  muscular  metabolism,  according 
to  which  the  chemical  processes  take  place  in  two  stages.  In  the 
first  the  complex  energy-yielding  material,  sugar,  for  example, 
undergoes  a  splitting  process  which  results  in  the  formation  of 
intermediary  products,  such  as  lactic  acid.  In  the  second  stage 
these  intermediary  products  or  some  of  them  are  oxidized,  provided, 
as  Fletcher  points  out,  there  is  an  adequate  supply  of  oxygen. 
Under  normal  conditions  a  sufficient  amount  of  oxygen  is  fur- 
nished by  the  circulating  blood,  but  under  pathological  conditions 
and  in  the  excised  muscle,  when  air  is  excluded,  the  supply  may  not 
be  adequate,  and  as  a  result  the  intermediary  products  are  not 
oxidized  completely.  Under  such  conditions  less  heat  is  produced 
in  the  muscle,  and  the  intermediary  products  accumulate  in  the 
tissue. 

The  general  views  here  stated  are  also  in  accord  with  the  facts 
regarding  heat  production  in  muscle  during  contraction,  as  stated 
on  p.  37.  The  so-called  delayed  heat  production  that  occurs  after 
the  mechanical  process  of  shortenng  is  past  is  probably  caused  by 
the  oxidation  of  the  intermediary  products,  the  lactic  acid  perhaps, 
and  Hill*  has  shown  that  when  oxygen  is  excluded,  this  second 
phase  in  heat  production  drops  out. 

Disappearance  of  the  Glycogen. — Satisfactory  proof  has  been  fur- 
nished that  the  amount  of  carbohydrate  in  a  muscle  disappears 
more  or  less  in  proportion  to  the  extent  and  duration  of  the  con- 
tractions, and  that  after  prolonged  muscular  activity,  especially 
in  the  starving  animal,  the  supply  may  be  exhausted  entirely.  In 
what  way  the  glycogen  is  consumed  is  not  completely  known;  the 
matter  is  discussed  in  the  next  paragraph  and  in  the  section  on 
Nutrition.  It  is,  perhaps,  the  general  belief  in  physiology  today 
that  under  normal  conditions  the  glycogen  of  the  muscle,  after 
*  Hill,  "Journal  of  Physiology,"  46,  28,  1913. 


THE    CHEMISTRY    OF    MUSCLE.  67 

being  changed  to  sugar,  undergoes  eventually  a  conversion  to  lactic 
acid  as  a  result  of  the  stimulus  that  induces  contraction,  and  that 
this  formation  of  lactic  acid  is  directly  or  indirectly  connected 
with  the  process  of  shortening. 

The  Formation  of  Lactic  Acid. — The  lactic  acid  that  is  present 
in  the  muscle  is  increased  in  quantity  by  muscular  activity.  At- 
tention was  first  called  to  this  point  by  du  Bois-Reymond,  who 
showed  that  the  reaction  of  the  tetanized  muscle  is  distinctly  acid, 
while  that  of  the  resting  muscle  is  neutral  or  slightly  alkaline. 
This  fact  can  be  demonstrated  by  the  use  of  litmus  paper,  but  per- 
haps more  strikingly  by  the  use  of  acid  fuchsin.*  If  a  solution  of 
acid  fuchsin  is  injected  under  the  skin  of  a  frog  it  is  gradually  ab- 
sorbed and  distributed  to  the  body  without  injuring  the  tissues. 
In  the  normal  media  of  the  body  this  solution  remains  colorless  or 
nearly  so.  If  now  one  of  the  legs  is  tetanized  the  muscles  take  on  a 
red  color,  showing  that  an  acid  is  produced  locally.  In  the  case  of 
the  frog's  muscle  it  is  stated  f  that  in  the  resting  condition  its 
reaction  expressed  in  terms  of  hydrogen  ion  exponent  is  equal  to 
pH  7.43,  about  the  alkalinity  of  blood.  When  stimulated  to  the 
point  of  fatigue  the  reaction  changes  to  the  acid  side,  pH  =  6.84. 
Experiments  have  been  made  by  a  number  of  observers  to  deter- 
mine quantitatively  the  amount  of  lactic  acid  in  the  resting  and  the 
worked  muscle  respectively.  The  most  satisfactory  results  have 
been  obtained  by  Fletcher  and  Hopkins.  J  These  observers  have 
shown  in  the  first  place  that  injury  to  a  muscle  causes  a  produc- 
tion of  lactic  acid,  and  that,  therefore,  the  usual  method  of  deter- 
mining the  amount  of  this  substance  in  supposedly  resting  muscle 
has  given  fallacious  results  owing  to  the  injury  inflicted  during  the 
process  of  extraction.  By  the  adoption  of  a  new  method  they  have 
avoided  this  error,  and  they  find  that  in  resting  muscle  lactic  acid 
exists  in  traces  only  (0.03  per  cent.)  or  perhaps  is  absent  altogether. 
An  appreciable  amount  is  formed  when  the  excised  muscle  is 
well  tetanized  (0.22  per  cent.),  also  after  injury,  and  especially 
in  the  development  of  rigor.  In  heat-rigor  a  maximum  yield 
of  0.3  to  0.5  per  cent,  is  obtained  in  the  frog's  muscle.  In  a 
muscle  removed  from  the  body  and  deprived,  therefore,  of  its 
supply  of  oxygen,  lactic  acid  develops  rapidly,  reaching  finally 
an  amount  equal  to  that  observed  in  heat-rigor.  As  long  as 
such  a  surviving  muscle  shows  irritability  toward  artificial  stim- 
ulation, lactic  acid  continues  to  form.  When  irritability  is  lost, 
no  further  production  of  acid  can  be  detected  and  the  muscle 

*  Dreser,  "  Centralblatt  fiir  Physiologic,"  1,  195,  1887. 

fPechstein,  "  Biochemische  Zeitschrift,"  68,  140,  1915. 

j  Fletcher  and  Hopkins,  "Journal  of  Physiology,"  1907,  35,  247;  also 
1911,  12,  43,  286,  and  Embden  et  al.,  "Biochemische  Zeitschrift,"  1912,  45, 
45. 


68  THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 

soon  goes  into  death-rigor.  On  the  contrary,  if  the  muscle  is 
supplied  abundantly  with  oxygen,  no  accumulation  of  lactic  acid 
can  be  detected.  It  is  evident  from  these  observations  that 
lactic  acid  is  formed  in  the  muscle  as  a  result  of  the  chemical 
changes  underlying  contraction,  and  also  of  the  changes  that 
occur  during  dying.  The  interpretation  of  this  fact  and  also 
of  the  further  fact  that  the  lactic  acid  does  not  appear  when 
oxygen  is  freely  supplied  to  the  muscle  is  surrounded  with  diffi- 
culties owing  to  our  lack  of  knowledge  of  the  chemical  reactions 
that  take  place.  The  simplest  explanation  at  present  is  that  the 
lactic  acid  is  an  intermediary  product  formed  from  the  sugar  by 
enzyme  action,  and  that  it  subsequently,  in  the  presence  of  oxygen, 
undergoes  oxidation  under  the  influence  of  other  enzymes;*  but 
another  possible  explanation  is  that  the  lactic  acid,  after  causing 
in  some  way  the  process  of  contraction,  is  again  reconstructed  by 
synthesis  into  the  precursor  from  which  it  was  derived.  The  fact 
that  immediately  after  the  shortening  of  the  muscle  there  occurs  an 
oxidative  process,  attended  by  liberation  of  heat  and  carbon  dioxid, 
shows  that  some  material  is  oxidized,  either  lactic  acid  or  some 
other  product  derived  from  the  sugar.  The  significance  of  this 
reaction  has  been  interpreted  differently  by  various  authors.  The 
energy  liberated  may  be  used  in  the  synthesis  of  the  lactic  acid  to 
sugar,  or,  more  probably  (Fletcher  and  Hopkins),  assuming  that  it 
is  the  lactic  acid  itself  that  is  burnt,  it  may  be  utilized  to  restore 
potential  energy  to  the  muscle  by  re-establishing  the  physico- 
chemical  condition  that  existed  before  the  contraction  took  place. 
On  the  chemical  side  much  uncertainty  exists  in  regard  to  the 
origin  as  well  as  the  fate  of  the  lactic  acid.  In  a  general  or  sche- 
matic way  we  may  adopt  the  hypothesis  that  the  lactic  acid  is 
derived  from  the  sugar,  and  this,  in  turn,  from  the  reserve  supply  of 
carbohydrate  (glycogen),  but  the  steps  in  the  process  are  not 
known.  There  is  reason  to  believe  that  the  lactic  acid  is  not  de- 
rived directly  from  sugar  but  from  some  unknown  compound 
formed  from  the  sugar.  One  group  of  workers  f  designate  this 
unknown  precursor  of  lactic  acid  as  ladacidogen  to  emphasize  its 
characteristic  as  a  mother  substance  of  the  lactic  acid.  On  the 
other  hand,  it  is  supposed  that  the  change  to  lactic  acid  takes 
place  not  in  one  step  but  through  intermediate  stages.  A  further 
discussion  in  regard  to  this  point  will  be  found  on  page  916. 

Chemical  Changes  During  Rigor  Mortis. — The  chemical 
changes  during  rigor  have  been  referred  to  above,  but  may  be 
summarized  here  in  brief  form: 

*  Fletcher  and  Hopkins,  Croonian  Lecture,  "Proc.  Royal  Soc.,"  London, 
B.  89,  444,  1917. 

f  Embden  et  al,  "Zeitschrift.  f.  physiol.  Chemie,"  93,  1,  1914. 


THE    CHEMISTRY    OF    MUSCLE.  69 

1.  There  is  a  coagulation  of  the  protein  material  of  the  muscle 
plasma,  which  at  present  may  be  explained  by  supposing  that  the 
contained  myosin  and  myogen,  spontaneously,  or  under  the  action 
of  acid  products  of  metabolism,  pass  into  their  insoluble  forms, — 
namely,  myosin  fibrin  and  myogen  fibrin. 

2.  There  is  an  increased  acidit}^  due  to  a  production  of  lactic 
acid. 

3.  There   is   a   production   of   CO2.     Much   importance   was 
attributed  formerly  to  this  product  on  the  belief  that  it  indicated 
the  occurrence  of  a  metabolic  reaction,  a  catabolic  or  oxidative 
change   similar  to   that  taking  place  in   contraction.     Fletcher 
and  Brown*  give  proof,  however,  so  far  at  least  as  heat  rigor  and 
chloroform  rigor  are  concerned,  that  the  C02  formed  does  not  arise 
from  a  metabolic  breakdown  of  organic  material,  but  is  simply  an 
indirect  result  of  the  production  of  acid.     This  acid  as  it  accumu- 
lates acts  upon  the  carbonates  in  the  muscle  and  thus  leads  to  a 
liberation  of  the  CO2.     From  this  standpoint  the  CO2  production 
in  rigor  as  it  usually  occurs  has  no  physiological  significance.     If, 
however,  the  muscle  during  the  development  of  rigor  is  supplied 
plentifully  with  oxygen,  then  the  lactic  acid,  as  it  is  formed,  under- 
goes oxidation,  with  the  production  of  CO2.    According  to  condi- 
tions the  CO2  may  have  two  origins.     In  the  absence  of  oxygen  it 
is  derived  from  the  action  of  the  lactic  acid  on  the  alkaline  car- 
bonates, while  in  the  presence  of  oxygen  an  additional  amount  is 
formed  by  oxidation  of  the  lactic  acid  itself. 

4.  The  consumption  of  glycogen.     According  to  recent  ob- 
servers, carbohydrate  disappears  during  rigor  as  it  does  during 
contraction,  and  the  loss  in  carbohydrate  runs   parallel  to  the 
increase  in  lactic  acid,  f 

The  Relation  of  the  Chemical  Changes  during  Contraction 
to  Fatigue;  Chemical  Theory  of  Fatigue. — As  we  have  seen,  a 
muscle  kept  in  continuous  contraction  soon  shows  fatigue  ;  it 
relaxes  more  and  more  until,  in  spite  of  constant  stimulation,  it 
becomes  completely  unirritable.  We  may  define  fatigue,  there- 
fore, as  a  more  or  less  complete  loss  of  irritability  and  contractility 
brought  on  by  functional  activity.  But  even  when  the  fatigue  is 
complete  and  the  muscle  fails  to  respond  at  all  to  maximal 
stimulation,  a  very  short  interval  of  rest  is  sufficient  to  bring  about 
some  return  of  irritability.  For  a  complete  restoration  to  its 
normal  condition  a  long  interval  of  time  may  be  necessary.  If 
the  muscle  is  isolated  from  the  body  and  is  thus  deprived  of  its 
circulation  and  its  proper  supply  of  oxygen,  fatigue  appears 
more  rapidly  and  is  recovered  from  less  completely.  Ranke,t 

*  Fletcher  and  Brown,  "Journal  of  Physiology,"  48,  177,  1914. 
t  Parnas  and  Wagner,  "Biochem.  Zeit.,"  1914,  61,  387. 
j  Ranke,  "Tetanus,"  Leipzig,  1865. 


70  THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 

to  whom  we  owe  the  first  thorough  investigation  of  this  subject, 
was  led  to  believe  that  as  a  result  of  the  chemical  changes  occur- 
ring in  the  muscle  during  contraction  certain  substances  are 
formed  which  depress  or  inhibit  the  power  of  contraction.  In 
support  of  this  view  he  found  that  extracts  made  from  the 
fatigued  muscles  of  one  frog  when  injected  into  the  circulation 
of  another  fresh  frog  would  bring  on  the  appearance  of  fatigue 
in  the  latter.  Control  experiments  made  with  extracts  of 
unfatigued  muscles  gave  no  such  result.  He  designated  these 
inhibitory  products  as  fatigue  substances  and  made  experiments 
to  prove  that  they  consist  of  the  known  products  of  muscular 
metabolism,  namely,  lactic  acid  (or  the  lactates),  carbon  dioxid, 
and  possibly  also  acid  potassium  phosphate  (KH2PO4).  These 
results  have  been  confirmed  by  other  observers,*  and  we  may  ac- 
cept, therefore,  the  view  that  the  products  of  muscular  activity, 
if  they  are  allowed  to  accumulate  in  the  muscle,  serve  to  diminish 
or  suppress  its  contractility,  and,  in  all  probability,  this  effect  is  due 
to  the  acidity  of  the  products  formed  (lactic  acid,  carbon  dioxid). 
We  know' that  when  muscular  activity  is  prolonged,  or  is  carried 
out  under  conditions  which  imply  a  lessened  supply  of  oxygen,  an 
accumulation  of  some  of  these  products  does  actually  occur.  It  is 
possible,  of  course,  that  other  intermediary  substances  are  formed 
which  may  have  a  similar  effect.  Thus  Weichardt  f  has  stated  that 
muscular  contractions  give  rise  to  a  definite  toxin,  derived  from  the 
protein  material  of  the  muscle,  which,  in  his  opinion,  is  the  chief 
agent  in  causing  fatigue.  He  claims  to  have  isolated  this  fatigue 
toxin  (kenotoxin)  to  the  extent  at  least  of  having  freed  it  from 
the  above-mentioned  fatigue  substances  of  Ranke.  When 
injected  into  the  circulation  of  a  fresh  animal,  it  brings  on  fatigue 
or  even  death.  Moreover,  by  injecting  it  in  suitable  doses,  the 
body  may  form  an  antitoxin,  and  this  latter  substance,  when  given 
to  a  fresh  animal,  may  confer  upon  it  an  unusual  capacity  for 
performing  muscular  work.  It  is  not  advisable,  however,  to 
accept  these  statements  until  the  facts  have  been  corroborated 
by  other  observers  and  further  experiments.  At  present  we  are 
justified  only  in  laying  emphasis  upon  the  known  products  of  mus- 
cular metabolism,  particularly  the  lactic  acid.  When  this  sub- 
stance accumulates  in  the  muscle  it  may  be  carried  off  in  the 
blood  and  thus  influence  other  organs.  On  such  a  supposition  we 
may  explain  the  fact,  brought  out  by  ergographic  experiments,  that 
marked  exercise  of  one  set  of  muscles,  for  example,  those  of  the  legs 

*Lee,  "American  Journal  of  Physiology,"  1907,  20,  170,  and  Burridge, 
"Journal  of  Physiology,"  1911,  41,  285. 

t  Weichardt,  "Archiv  f.  Anat.  u.  Physiol.  (physiol.  Abth.),"  1905,  219; 
also"Miinchener  med.  Wochenschrift,"  1904,  1905,  1906. 


THE    CHEMISTRY    OF    MUSCLE.  71 

in  walking  or  climbing,  may  diminish  the  amount  of  work  obtainable 
from  other  unused  muscles,  such  as  those  of  the  arms.  So  also  the 
effect  of  muscular  exercise  upon  the  rate  of  the  respiratory  move- 
ments and  upon  the  heart-rate  is  explained,  as  we  shall  see,  in  a 
similar  way.  It  should  be  added  that  Lee.*  confirming  an  older 
observation  by  Ranke,  has  published  experiments  which  indicate 
that  the  first  effect  of  the  so-called  fatigue  substances  is  to  increase 
the  irritability  of  the  muscle,  while  the  later  effect  is  to  diminish  the 
irritability  or  to  suppress  it  altogether.  In  this  initial  favoring  in- 
fluence Lee  finds  an  explanation  of  the  phenomenon  of  Treppe  (see 
p.  35).  After  the  appearance  of  complete  fatigue  a  muscle  shows 
usually  some  return  of  irritability  if  given  a  short  rest.  But  even  in 
the  case  of  a  muscle  in  the  body,  with  its  circulation  intact,  an 
interval  of  some  hours  is  required  before  it  regains  entirely  its  power 
to  perform  a  normal  amount  of  work.  It  seems  probable  that  the 
loss  of  power  to  do  work  is  referable  in  part  to  a  using  up  of  the 
supply  of  energy-yielding  material,  but  the  accumulation  of  the 
acid  fatigue  substances  is  doubtless  the  immediate  cause  of  the 
loss  of  irritability  which  we  usually  designate  as  fatigue. 

Theories  of  Muscle  Contraction. — It  is  generally  admitted  that  no  theory 
of  muscle  contraction  yet  proposed  is  satisfactory.  Such  a  theory  should 
explain  the  mechanism  by  means  of  which  the  shortening  of  the  muscle  is 
produced,  the  nature  of  the  engery  which  is  thus  transformed  into  mechanical 
work,  and  the  relation  of  this  energy  to  the  chemical  reaction  that  takes  place 
in  the  stimulated  muscle.  The  measurable  manifestations  of  energy  which 
are  observed  in  the  contracting  muscle  are  the  change  in  electric  potential, 
the  increased  production  of  heat,  and  the  mechanical  work.  The  electrical 
change  is  a  fleeting  phenomenon  which  passes  rapidly  over  the  muscle,  starting 
from  the  point  stimulated.  Whether  this  electrical  change  is  simultaneous 
with  the  chemical  reaction  or  precedes  it  cannot  be  stated  definitely,  although 
simultaneous  records  indicate  that  the  electrical  change  begins  at  least  before 
either  the  mechanical  or  the  thermal  changes  can  be  recorded.  The  usual  point 
of  view  in  physiology  has  been  that  the  chemical  change  caused  by  the  stimu- 
lus or  products  formed  from  this  change  give  origin  to  all  the  forms  of  energy, 
electrical,  mechanical,  and  thermal,  which  are  exhibited  by  the  contracting 
muscle.  The  older  view  was  to  compare  the  muscle  to  a  heat  engine  in  which 
the  potential  chemical  energy  of  the  fuel  is  first  converted  to  heat  by  combus- 
tion, and  then  by  appropriat3  mechanisms  a  portion  of  this  heat  energy  is  utilized 
to  perform  mechanical  work.  Engelmannf  has  furnished  a  specific  hypothesis 
of  this  character.  He  assumes  that  the  chemical  energy  set  free  in  the  muscle 
takes  the  form  of  heat,  which  then  acts  upon  the  doubly  refractive  particles 
in  the  dim  bands  of  the  muscular  fibrillae  and  causes  them  to  imbibe  water 
from  the  adjoining  light  bands.  If  the  doubly  refractive  particles  are  supposed 
to  have  a  linear  shape,  then,  by  imbibition,  they  would  tend  to  assume  a  spher- 
ical form,  and  thus  there  would  occur  a  shortening  along  one  diameter  and  an 
increase  along  the  diameter  at  right  angles,  such  as  occurs  in  the  contracting 
muscle.  As  the  muscle  cools  down  the  water  passes  back  into  the  light  bands 

*  For  discussion  and  experiments,  see  Lee,  Harvey  Lectures,  1905-06, 
Philadelphia,  1906;  also  "Journal  of  the  American  Medical  Association,"  May 
19,  1906,  "American  Journal  of  Physiology,"  18,  267,  1907. 

t  Engelmann,  "Ueber  den  Ursprung  der  Muskelkraft,"  Leipzig,  1893: 
also  Pfliiger's  "  Archiv,"  1873,  p,  155. 


72 


THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE. 


Fig.  27. — Engelmann's  artificial  muscle.  The  artificial  muscle  is  represented  by  the  cat- 
gut string,  m.  This  is  surrounded  by  a  coil  of  platinum  wire,  w,  through  which  an  electrical 
current  may  be  sent.  The  catgut  is  attached  to  a  lever,  h,  whose  fulcrum  is  at  c.  The  catgut 
is  immersed  in  a  beaker  of  water  at  50°  to  55°  C.,  and  "stimulated  "  by  the  sudden  increase 
in  temperature  caused  by  the  passage  of  a  current  through  the  coil. — (After  Engelmann.) 


Fig.  28. — Curve  of  simple  contraction  obtained  from  an  artificial  muscle.  The  dura- 
tion of  the  stimulus  (heating  effect  caused  by  the  current)  is  shown  by  the  break  in  the 
line  beneath  the  curve. 

and  the  phase  of  relaxation  takes  place.  He  has  supported  this  hypothesis 
by  microscopical  observations  upon  the  relations  of  the  dim  and  light  bands 
in  the  contracted  and  relaxed  fibrils  (p.  20),  and,  moreover,  has  constructed 


THE    CHEMISTRY    OF    MUSCLE.  73 

an  artificial  muscle  from  a  string  of  catgut  which,  working  on  this  principle, 
contracts  when  heated  and  relaxes  when  cooled.  When  the  heating  occurs 
suddenly  this  model  gives  curves  of  contraction  identical  with  those  obtained 
from  plain  muscle.  The  apparatus  is  illustrated  and  described  in  Fig.  27, 
and  the  curve  of  contraction  obtained  from  it  is  shown  in  Fig.  28.  The  under- 
lying principle  of  this  hypothesis  has  met  with  much  criticism.  Fick  *  has 
shown  apparently  that  when  applied  quantitatively  to  the  work  done  by  muscle 
it  leads  to  an  impossible  conclusion.  If,  in  a  reversible  process,  at  a  temper- 
ature TO,  a  certain  quantity  of  heat,  Qo,  is  converted  to  mechanical  work,  it 
necessitates,  according  to  the  second  law  of  Thermodynamics,  the  passage  of 
heat,  Q,  from  a  higher  temperature,  T!  to  a  lower  temperature,  T2,  in  accordance 


with  the  equation,  ^  =  Q  ( ~  -  4~  \ 

J-O  \    A2  Al   / 


We  may  assume,  in  accordance  with  experimental  results,  that  the  efficiency 
of  muscle  is  equal  to  25  per  cent,  of  the  total  energy,  or  that  Q0  =  iQ,  and  that 
Tj  is  the  temperature  of  the  body,  37°  C.,  or  expressed  in  the  absolute  scale, 
37°  +  273°  =  310°  C.  T0  is  the  same  as  Tt.  If,  now,  in  the  equation  we  sub- 
stitute iQ  for  Qo  and  310°  C.  for  T2  and  solve  the  equation  for  T!  it  gives  a 
value  of  387°  C.,  or,  expressed  in  centigrade  units,  387°— 273°  =  114°  C. 
That  is  to  say,  to  perform  the  work  indicated  the  muscle  must  show  a  fall 
in  temperature  from  114°  to  37°  C.,  and  it  seems  clearly  impossible  to  sup- 
pose that  the  muscle  in  contracting  attains  any  such  temperature  as  114°  C. 

This  criticism  has  been  accepted  by  most  authors  as  demonstrating  that  the 
muscle  cannot  work  as  a  heat  engine  by  transforming  a  part  of  the  heat  of  the 
chemical  reaction  to  work.  A  difference  in  temperature  is  necessary  that  is 
not  possible  in  the  case  of  muscle.  Other  theories  have  been  proposed,  accord- 
ing to  which  the  chemical  energy  is  supposed  to  be  converted  into  work  either 
directly  (Fick)  or  through  a  change  in  surface  tension.  The  muscle  is  supposed 
to  act  in  such  theories  as  a  chemical  or  chemodynamic  engine.  The  various 
forms  which  the  theories  employing  the  conception  of  surface  tension  have 
taken  make  it  difficult  to  describe  them  in  general  terms.  According  to  one 
presentation  (Macallumf)  the  sarcous  elements  (dim  bands)  may  be  considered 
as  having  interfaces  with  the  sarcoplasm  along  the  lateral  planes  and  with  the 
isotropic  substance  (light  bands)  at  their  ends,  at  which  surface  tension  exists. 
If  the  results  of  the  chemical  changes  within  the  elements  are  such  as  to  cause 
a  diminution  in  surface  tension  along  the  lateral  walls,  or  an  increase  in  this 
energy  at  the  end  surfaces,  the  elements  would  tend  to  change  from  a  cylinder 
with  straight  to  one  with  curved  lateral  walls,  and  this  change,  when  multi- 
plied by  the  total  number  of  sarcous  elements  in  the  muscle,  would  account 
for  the  shortening.  The  theory  is  deficient  in  not  explaining  how  the  surface 
energy  is  changed,  and  also  in  failing  to  give  an  approximate  quantitative 
determination  of  the  total  amount  of  mechanical  energy  that  might  be  obtained 
in  this  way  from  the  muscle.  According  to  calculations  made  by  Bernstein,  j 
the  work  energy  exhibited  by  a  contracting  muscle  is  greater  than  can  be 
accounted  for  by  probable  changes  in  surface  tension. 

Another  theory  has  been  adopted  in  recent  years  by  an  increasing  number 
of  workers,  and  has  been  supported  by  many  suggestive  experiments.  This 
theory  holds  that  the  shortening  of  muscle  in  contraction  is  essentially  a 
phenomenon  of  imbibition.  The  instrument  by  which  the  shortening  is 
effected  is  the  fibril,  which  is  regarded  as  a  coherent  gel  structure  embedded  in 
a  more  liquid  material,  the  sarcoplasm.  When  the  muscle  is  stimulated,  lactic 
acid  is  formed  in  the  fibril  or  in  the  sarcoplasm  around  it,  and  the  effect  of  this 
acid  is  to  increase  the  power  of  imbibition  of  the  fibril  or  of  certain  structures  in 
it,  for  example,  the  anisotropous  discs.  The  swelling  thus  produced  causes  the 
shortening  of  the  muscle,  and  the  subsequent  relaxation  is  explained  as  due  to 
the  removal  of  the  acid  by  diffusion  or  by  oxidation.  The  heat  developed  in 

*  Fick-Pfluger's  "Archiv,"  1893,  53,  606. 

t  Macallum,  "  Surface  Tension  and  Vital  Phenomena,"  University  of 
Toronto  Studies,  Physiological  Series,  No.  8,  1912. 

I  Bernstein-Pfluger's  "Archiv,"  85,  271,  1901.  See  also  Berg,  "Biochem- 
ical Bulletin,"  2,  101,  1912. 


74         THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE. 

the  muscle  after  the  phase  of  shortening  is  past  has  been  connected  with  this 
latter  process,  namely,  the  oxidative  destruction  of  the  lactic  acid,  although 
some  authors  contend  that  the  lactic  acid  is  not  removed  by  oxidation  to  CO2 
and  H2O,  but  is  resynthesized  to  the  sugar  or  the  sugar-complex  from  which  it 
was  derived.  The  heat  produced  in  the  oxidation  is  liberated  in  part  as  free 
heat  which  warms  the  muscle,  and  in  part  may  be  stored  in  the  muscle  in  some 
form  of  potential  energy,  so  that  as  an  apparatus  for  the  performance  of 
mechanical  work  the  muscle  is  restored  to  its  status  quo  ante.  The  theory  has 
many  variations  as  regards  details,  but  the  central  point  is  that  the  lactic  acid 
is  the  agent  which  causes  the  contraction  by  its  action  on  the  imbibition 
properties  of  the  fibril.  The  shortening  in  rigor  mortis  is  explicable  in  the  same 
way  as  an  acid  effect.* 

*  For  various  expressions  of  this  theory,  consult  McDougall,  "Journal  of 
Anatomy  and  Physiology,"  31,  410,  1897,  and  32,  187,  1898.  Meigs,  "Amer- 
ican Journal  of  Physiology,"  26,  191,  1910,  and  22,  477,  1908.  Fletcher  and 
Brown,  "Journal  of  Physiology,"  48,  177,  1914.  Hill,  ibid.,  46,  28,  1913. 
Pauli, " Kolloid-chemie  der  Muskelkontraktion,"  1912.  Fletcher  and  Hopkins, 
Croonian  Lectures,  "Proceedings  Royal  Society,"  B.  89,  444,  1917. 


CHAPTER  III. 

THE  PHENOMENON  OF  CONDUCTION— PROPERTIES 
OF  THE  NERVE  FIBER. 

Conduction. — When  living  matter  is  excited  or  stimulated  in 
any  way  the  excitation  is  not  localized  to  the  point  acted  upon, 
but  is  or  may  be  propagated  throughout  its  substance.  This  prop- 
erty of  conducting  a  change  that  has  been  initiated  by  a  stimulus 
applied  locally  is  a  general  property  of  protoplasm,  and  is  exhib- 
ited in  a  striking  way  by  many  of  the  simplest  forms  of  life.  A 
light  touch,  for  instance,  applied  to  a  vorticella  will  cause  a  retrac- 
tion of  its  vibrating  cilia  and  a  shortening  of  its  stalk.  In  the  most 
specialized  animals,  such  as  the  mammalia,  this  property  of  con- 
duction finds  its  greatest  development  in  the  nervous  tissue, 
especially  in  the  axis  cylinder  processes  of  the  nerve  cells,  the 
so-called  nerve  fibers.  But  the  property  is  exhibited  also  to  a 
greater  or  less  extent  by  other  tissues.  When  a  muscular  mass  is 
stimulated  at  one  point  the  excitation  set  up  may  be  propagated 
not  only  through  the  substance  of  the  cells  or  fibers  directly  affected, 
but  from  cell  to  cell  for  a  considerable  distance.  In  the  heart 
tissue  and  in  plain  muscle  it  has  been  shown  that  a  change  of 
this  sort  may  be  conducted  independently  of  the  phenomenon 
of  visible  contraction.  A  stimulus  applied  to  the  venous  end 
of  a  frog's  heart,  for  instance,  may,  under  certain  conditions, 
be  conducted  through  the  auricular  tissue  without  causing  in  it  a 
visible  change,  and  yet  arouse  a  contraction  in  the  ventricular 
muscle  (Engelmann).  Similarly,  it  can  be  shown  that  ciliary 
cells  can  convey  a  stimulus  from  cell  to  cell.  A  stimulus  applied 
to  one  point  of  a  field  of  ciliary  epithelium  may  set  up  a  change 
that  is  conveyed  as  a  ciliary  impulse  to  distant  cells.  The 
universality  of  this  property  of  conduction  in  the  simpler,  less 
differentiated  forms  of  life,  and  its  presence  in  some  degree  in 
many  of  the  tissues  of  the  higher  forms  would  justify  the  as- 
sumption that  the  underlying  change  is  essentially  the  same  in 
all  cases.  But  in  nerve  fibers  this  property  has  become  special- 
ized to  the  highest  degree,  and  in  this  tissue  it  may  be  studied, 
therefore,  with  the  greatest  success  and  profit. 

Structure  of  the  Nerve  Fiber. — The  peripheral  nerve  fiber, 
as  we  find  it  in  the  nerve  trunks  and  nerve  plexuses  of  the  body, 
may  be  either  medullated  or  non-medullated.  All  the  nerve  fibers 
that  arise  histologically  from  the  nerve-cells  of  the  central  nervous 

75 


76  THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 

system  proper — the  brain  and  cord  and  the  outlying  sensory 
ganglia  of  the  cranial  nerves  and  the  posterior  spinal  roots — are 
medullated.  These  fibers  contain  a  central  core,  the  axis  cylinder, 
which  is  usually  regarded  as  an  enormously  elongated  process  of 
the  nerve  cell  with  which  it  is  connected.  The  axis  cylinder  shows 
a  differentiation  into  fibrils  (neurofibrils)  and  interfibrillar  sub- 
stance (neuroplasm).  All  of  our  evidence  goes  to  show  that  the 
axis  cylinder  is  the  essential  part  of  the  nerve  fiber  so  far  as  its 
property  of  conduction  is  concerned.  It  is  further  assumed  that 
the  neurofibrils  in  the  axis  cylinder  form  the  conducting  mech- 
anism rather  than  the  interfibrillar  substance.  Surrounding  the 
axis  cylinder  we  have  the  medullary  or  myelin  sheath,  varying 
much  in  thickness  in  different  fibers.  This  sheath  is  composed  of 
peculiar  material  and  is  interrupted  or  divided  into  segments  at  cer- 
tain intervals,  the  so-called  nodes  of  Ranvier.  Outside  the  myelin 
there  is  a  delicate  elastic  sheath  comparable  to  the  sarcolemma  of 
the  muscle  fiber  and  designated  as  the  neurilemma.  Lying  under 
the  neurilemma  are  found  nuclei,  one  for  each  internodal  segment 
of  the  myelin,  surrounded  by  a  small  amount  of  granular  proto- 
plasm. The  non-medullated  fibers  have  no  myelin  sheath.  They 
are  to  be  considered  as  an  axis  cylinder  process  from  a  nerve  cell, 
surrounded  by  or  inclosed  in  a  neurilemmal  sheath.  These  fibers 
arise  histologically  from  the  nerve  cells  found  in  the  outlying 
ganglia  of  the  body,  the  ganglia  of  the  sympathetic  system  and 
its  appendages. 

The  Function  of  the  Myelin  Sheath. — The  myelin  sheath  of 
the  cerebrospinal  nerve  fibers  is  a  structure  that  is  interesting  and 
peculiar,  both  as  regards  its  origin  and  its  composition.  Much 
speculation  has  been  indulged  in  with  regard  to  its  function,  but 
practically  nothing  that  is  certain  can  be  said  upon  this  point.  It 
has  been  supposed  by  some  to  act  as  a  sort  of  insulator,  preventing 
.contact  between  neighboring  axis  cylinders  and  thus  insuring 
better  conduction.  But  against  this  view  it  may  be  urged  that 
we  have  no  proof  that  the  non-medullated  fibers  do  not  conduct 
equally  as  well.  The  view  has  some  probability  to  it,  however, 
for  we  must  remember  that  the  non-medullated  fibers  do  not  run 
in  large  nerve  trunks  that  supply  a  number  of  different  organs, 
and  therefore  in  them  a  provision  for  isolated  conduction  is  not  so 
necessary.  Moreover,  in  the  medullated  fibers  the  myelin  sheath 
is  lost  toward  its  peripheral  end  after  the  nerve  has  entered  the 
tissue  to  which  it  is  to  be  distributed,  indicating  that  its  function 
is  then  no  longer  necessary.  According  to  the  older  conceptions 
of  the  process  of  conduction  in  nerve  fibers,  not  only  anatomical 
but  also  physiological  continuity  is  necessary.  Mere  contact  of 
living  axis  cylinders  would  not  enable  the  nerve  impulse  to  pass 


THE  PHENOMENON  OF  CONDUCTION.  77 

from  one  to  the  other.  The  newer  views,  included  in  the  so-called 
neuron  theory,  assume  that  mere  contact  of  living,  entirely  normal 
nerve  substance  does  permit  an  excitatory  change  to  pass  from  one 
to  the  other,  so  that  it  is  not  impossible  that  the  myelin  sheath 
may  serve  to  prevent  one  axis  cylinder  from  influencing  the  neigh- 
boring axis  cylinders  in  a  nerve  trunk. 

As  some  evidence  for  this  view,  attention  has  been  called  to  the  fact  that 
in  the  condition  known  as  multiple  or  insular  sclerosis  of  the  brain  and  cord 
the  axis  cylinders  of  the  areas  affected  remain  intact,  while  the  myelin  sheaths 
are  destroyed.  The  disturbances  of  co-ordination  accompanying  this  condi- 
tion may  be  an  expression,  therefore,  of  a  loss  of  isolated  conduction. 

Others  have  supposed  that  the  myelin  sheath  serves  as  a  source 
of  nutrition  to  the  inclosed  axis  cylinder,  or  as  a  regulator  in  same 
way  of  its  metabolism.  No  fact  is  reported  that  would  make  this 
suggestion  seem  probable,  except,  perhaps,  the  statement  that 
stimulation  of  a  nerve,  even  for  a  brief  period,  causes  a  change 
in  the  appearance  of  the  neurokeratin  framework  found  in  the 
myelin  sheath.  The  change  consists  in  a  widening  of  the  meshes 
(Stiibel*).  In  general,  it  is  found  that  the  myelin  sheath  is  larger 
in  those  fibers  that  have  the  longest  course;  the  size  of  the  sheath, 
in  fact,  increases  with  that  of  the  axis  cylinder.  It  is  known 
also  that  the  medullated  fibers  in  general  are  more  irritable  to 
artificial  stimuli  than  the  non-medullated  ones,  and  that  when 
induction  shocks  are  employed,  the  non-medullated  fibers  lose 
their  irritability  more  rapidly  at  the  point  stimulated.  None 
of  these  facts  are  sufficient,  however,  to  indicate  the  probable 
function  of  the  myelin.  The  embryological  development  of  the 
sheath  also  fails  to  throw  light  on  its  physiological  significance. 
For,  while  it  is  usually  supposed  that  the  axis  cylinder  itself  is 
simply  an  outgrowth  from  the  nerve  cell,  and  the  myelin  sheath 
arises  from  separate  mesoblastic  cells  which  surround  the  axis 
cylinder,  this  view,  so  far  as  the  myelin  is  concerned,  is  not  beyond 
question,  and  the  study  of  the  process  of  regeneration  of  nerve 
fibers  indicates  that  the  actual  production  of  myelin  is  controlled 
in  some  way  by  the  functional  axis  cylinder.  The  axis  cylinder 
outgrowths  from  the  sympathetic  nerve  cells  found  in  the  ganglia 
of  the  sympathetic  chain  and  in  the  peripheral  ganglia  generally 
of  the  body  are  usually  non-medullated,  although  apparently 
this  is  not  an  invariable  rule.  In  the  birds  all  such  fibers,  on  the 
contrary,  are  medullated  (Langleyf).  Nothing  is  known  as  to 
the  conditions  that  determine  whether  a  nerve-fiber  process  shall 
or  shall  not  be  surrounded  by  a  myelin  sheath. 

Chemistry  of  the  Nerve  Fiber.— Our  knowledge  of  the  chem- 
istry of  the  nerve  fibers  is  very  incomplete.     The  myelin  sheath 
*  Stubel,  "Pfliiger's  Archiv,"  1912,  149,  1. 
t  Langley,  "Journal  of  Physiology,"  30,  221,  1903;  20,  55,  1890. 


78          THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE. 

is  composed  largely  of  bodies  to  which  the  general  name  of  "  li- 
poids  "  has  been  applied.  This  term  is  used  as  a  generic  name  for 
those  constituents  of  living  cells  which  can  be  extracted  by  ether 
or  similar  solvents.  It  is  a  biological  rather  than  a  chemical 
term.  By  extraction  of  myelin  with  hot  alcohol  a  complex  phos- 
phorus-containing substance  known  as  protagon  may  be  obtained 
in  crystalline  form.  This  substance  is,  however,  believed  now  to 
be  a  mixture  rather  than  a  definite  chemical  individual.  The 
most  important  substances  isolated  from  the  myelin  are  lecithin 
(phosphatids)  ,  cholesterin,  and  the  cerebrosides. 

Lecithin  (C44H9oNPO9)  is  a  waxy  hygroscopic  yellowish  sub- 
stance containing  about  4  per  cent,  of  phosphorus.  When  de- 
composed by  the  action  of  alkalies  it  yields  as  split  products 
glycerophosphoric  acid,  a  nitrogenous  base,  cholin  (C5H15NO2), 
and  some  of  the  higher  fatty  acids,  such  as  oleic,  palmitic,  or 
stearic.  The  lecithins  constitute  one  member  of  a  larger  group 
known  as  phosphatids,  which  are  characterized  by  the  presence  of 
both  phosphorus  and  nitrogen.  They  are  widely  distributed  in  the 
tissues  and  liquids  of  the  body,  but  are  especially  characteristic 
of  the  white  matter  of  the  nervous  system.  They  combine  easily 
with  other  substances,  such  as  proteins,  glucosides,  etc.,  and  it  is 
probable  that  lecithin  exists  in  some  such  combination  in  the 
myelin.  The  decomposition  of  the  lecithin  referred  to  above 
occurs  in  the  body  when  nerves  undergo  degeneration.  The 
presence  of  the  fatty  acid  liberated  under  such  circumstances  is 
demonstrated  by  the  well-known  reaction  with  osmic  acid  used  to 
detect  degenerated  nerve  fibers,  while  the  existence  of  cholin  has 
been  shown  by  Halliburton*  in  the  liquids  of  the  body,  not  only 
after  nerve-degeneration  produced  by  experimental  lesions,  but 
in  the  case  of  degenerative  diseases  of  the  nervous  system. 

Cholesterin  or  cholesterol  (C^H^O)  is  a  white  crystalline  sub- 
stance containing,  as  its  formula  shows,  neither  nitrogen  nor  phos- 
phorus. It  is  widely  distributed  among  the  tissues  of  the  body, 
and  in  an  isomeric  form,  phytocholesterin,  occurs  also  in  plants. 
In  the  animal  body  it  is  especially  abundant  in  the  white  matter 
of  the  nerves.  The  chemical  nature  of  cholesterin  has  long  been  a 
matter  of  uncertainty,  but  recent  work  indicates  that  it  belongs 
to  the  group  of  "terpenes"  heretofore  supposed  to  be  confined 
to  the  plant  kingdom.  It  is  given  the  formula  — 
CH-CH2-CH2-C17H2fl-CH 


CHOH 

*  Halliburton,  "British  Medical  Journal,"  1907,  May  4  and  11.  Also 
"Folia  Neuro-Biologica,"  1907,  i.,  38,  and  "Biochemistry  of  Muscle  and 
Nerve/'  Philadelphia,  1904. 


THE  PHENOMENON  OF  CONDUCTION.  79 

The  fact  that  lecithin  and  cholesterin  usually  occur  together 
has  suggested  that  they  have  some  physiological  connection.  It 
has  been  supposed,  for  example,  that  they  act  as  a  check  upon  each 
other.  Lecithin  under  certain  conditions  favors  hemolysis  of  red 
corpuscles,  or  the  action  of  lipase  on  fat,  while  cholesterin  inhibits 
both  of  these  activities.  No  application  of  this  antagonistic  rela- 
tionship is  possible  at  present  in  the  case  of  the  myelin  sheath. 

Cerebrosides  or  Cerebrogalaclosides. — This  name  is  given  to  a 
group  of  bodies  containing  nitrogen,  but  no  phosphorus.  In  the 
myelin  they  are  found  in  connection  with  and  possibly  in  com- 
bination with  the  lecithin.  They  belong  to  the  group  of  glucosides, 
that  is,  on  hydrolytic  decomposition  they  give  rise  to  a  carbo- 
hydrate group,  in  this  case  galactose.  Fatty  acids  and  a  nitrogenous 
base  also  result  from  this  decomposition.  The  cerebroside  material 
obtained  from  the  white  matter  has  been  named  specifically 
cerebrin  or  phrenosin,  but  little  is  known  of  its  exact  structure. 

Union  of  Nerve  Fibers  into  Nerves  or  Nerve  Trunks. — The 
assembling  of  nerve  fibers  into  larger  or  smaller  nerve  trunks  re- 
sembles histologically  the  combination  of  muscle  fibers  to  form  a 
muscle.  Physiologically,  however,  there  is  no  similarity.  The 
various  fibers  in  a  muscle  act  together  in  a  co-ordinated  way  as  a 
physiological  unit.  On  the  other  hand,  the  hundreds  or  thou- 
sands of  nerve  fibers  found  in  a  nerve  may  form  groups  which  are 
entirely  independent  in  their  physiological  activity.  In  the 
vagus  nerve,  for  instance,  we  have  nerve  fibers  running  side  by 
side,  some  of  which  supply  the  heart,  some  the  muscles  of  the 
larynx,  some  the  muscles  of  the  stomach  or  intestines,  some  the 
glands  of  the  stomach  or  pancreas,  and  so  on.  Nerves  are, 
therefore,  anatomical  units  simply,  containing  groups  of  fibers 
which  have  very  different  activities  and  which  may  function 
entirely  independently  of  one  another.  As  a  nerve-trunk  is  con- 
stituted it  consists  chiefly  of  the  connective  tissue  binding  the 
fibers  together.  It  is  estimated  (Ellison)  that  in  the  median  nerve 
the  connective  tissue  forms  63  per  cent,  of  the  whole  trunk,  while 
myelin  sheaths  make  up  28  per  cent.,  and  the  axis  cylinders  only 
9  per  cent. 

Afferent  and  Efferent  Nerve  Fibers. — The  older  physiologists 
believed  that  one  and  the  same  nerve  or  nerve  fiber  might  conduct 
sensory  impulses  toward  the  central  nervous  system  or  motor  im- 
pulses from  the  central  nervous  system  to  the  periphery.  Bell  and 
Magendie  succeeded  in  establishing  the  great  truth  that  a  nerve 
fiber  cannot  be  both  motor  and  sensory.  Since  their  time  it  has 
been  recognized  that  we  must  divide  the  nerve  fibers  connected 
with  the  central  nervous  system  into  two  great  groups :  the  efferent 
fibers,  which  carry  impulses  outwardly  from  the  nervous  system 


80  THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 

to  the  peripheral  tissues,  and  the  afferent  fibers,  which  carry  their 
impulses  inwardly, — that  is,  from  the  peripheral  tissues  to  the 
nerve  centers.  Under  normal  conditions  the  afferent  fibers  are 
stimulated  only  at  their  endings  in  the  peripheral  tissues,  in  the 
skin,  the  mucous  membranes,  the  sense  organs,  etc.,  while  the 
efferent  fibers  are  stimulated  only  at  their  central  origin, — that 
is,  through  the  nerve  cells  from  which  they  spring.  The  difference 
in  the  direction  of  conduction  depends,  therefore,  on  the  anatomical 
fact  that  the  efferent  fibers  have  a  stimulating  mechanism  at  their 
central  ends  only,  while  the  afferent  fibers  are  adapted  only  for 
stimulation  at  thsir  peripheral  ends. 

Classification  of  Nerve  Fibers. — In  addition  to  this  funda- 
mental separation  we  may  subdivide  peripheral  nerve  fibers  into 
smaller  groups,  making  use  of  either  anatomical  or  physiological 
differences  upon  which  to  base  a  classification.  For  the  purpose 
here  in  view  a  classification  that  is  physiological  as  far  as  possible 
seems  preferable.  In  the  first  place,  experimental  physiology  has 
shown  that  the  effect  of  the  impulse  conveyed  by  nerve  fibers  may 
be  either  exciting  or  inhibiting.  That  is,  the  tissue  or  the  cell 
to  which  the  impulse  is  carried  may  be  thereby  stimulated  to  ac- 
tivity, in  which  case  the  effect  is  excitatory,  or,  on  the  contrary, 
it  may,  if  already  in  activity,  be  reduced  to  a  condition  of  rest  or 
lessened  activity;  the  effect  in  this  case  is  inhibitory.  Many 
physiologists  believe  that  one  and  the  same  nerve  fiber  may  carry 
excitatory  or  inhibitory  impulses,  but  in  some  cases  at  least  we 
have  positive  proof  that  these  functions  are  discharged  by  separate 
fibers.  We  may  subdivide  both  the  afferent  and  the  efferent  sys- 
tems into  excitatory  and  inhibitory  fibers.  Each  of  these  sub- 
groups again  falls  into  smaller  divisions  according  to  the  kind  of 
activity  it  excites  or  inhibits.  In  the  efferent  system,  for  instance, 
the  excitatory  fibers  may  cause  contraction  or  motion  if  they  ter- 
minate in  muscular  tissue,  or  secretion  if  they  terminate  in  glandu- 
lar tissue.  For  convenience  of  description  each  of  the  groups  in 
turn  may  be  further  classified  according  to  the  kind  of  muscle  in 
which  it  ends  or  the  kind  of  glandular  tissue.  In  the  motor  group 
we  speak  of  vasomotor  fibers  in  reference  to  those  that  end  in  the 
plain  muscle  of  the  walls  of  the  blood-vessels;  visceromotor  fibers, 
those  ending  in  the  muscular  tissue  of  the  abdominal  and  thoracic 
viscera;  pilomotor  fibers,  those  ending  in  the  muscles  attached  to 
the  hair  follicles.  The  classification  that  is  suggested  in  tabular 
form  below  depends,  therefore,  on  three  principles:  first,  the  direc- 
tion in  which  the  impulse  travels  normally;  second,  whether  this 
impulse  excites  or  inhibits;  third,  the  kind  of  action  excited  or 
inhibited,  which  in  turn  depends  upon  the  kind  of  tissue  in  which 
the  fibers  end. 


THE  PHENOMENON  OF  CONDUCTION. 


81 


Efferent 


Afferent 


Excitatory 


Inhibitory 


Excitatory 


Motor 


Secretory 

Inhibi  to-mo- 
tor 

Inhibito-se- 
cretory 


Sensory 


fg 
II 


Inhibitory       •! 


He  Hex 


Inhibito-re- 
flex 


Motor. 

Vasomotor. 

Cardioinotor. 

Visceromotor. 

Pilomotor. 

Salivary, 
astric. 

Pancreatic. 

Sweat. 

Subdivisions  corresponding  to  the  varieties  of  mo- 
tor fibers  above. 

Subdivisions  corresponding  to  the  varieties  of  se- 
cretory fibers  above. 

Visual. 

Auditory. 

Olfactory. 

Gustatory. 

Pressu  re. 

Temperature. 

Pain. 

Hunger. 

Thirst,  etc. 

According  to  the  efferent  fibers  affected. 

Inhibitory  effects  upon  the  conscious  sensations  are 
not  demonstrated. 

The  reflex  fibers  that  cause  unconscious  reflexes 
are  known  to  be  inhibited  in  some  cases  at  least. 


That  the  final  action  of  a  peripheral  nerve  fiber  is  determined 
by  the  tissue  in  which  it  ends  rather  than  by  the  nature  of  the 
nerve  fiber  itself  or  the  nature  of  the  impulse  that  it  carries  is  indi- 
cated strongly  by  the  regeneration  experiments  made  by  Langley.* 
For  instance,  the  chorda  tympani  nerve  contains  fibers  which  cause 
a  dilatation  in  the  blood-vessels  of  the  submaxillary  gland,  while 
the  cervical  sympathetic  contains  fibers  which  cause  a  constriction 
of  the  vessels  in  the  same  gland.  If  the  lingual  nerve  (containing 
the  chorda  tympani  fibers)  is  divided  and  the  central  end  is  sutured 
to  the  peripheral  end  of  the  severed  cervical  sympathetic,  the 
chorda  fibers  will  grow  along  the  paths  of  the  old  constrictor  fibers 
of  the  sympathetic.  If  time  is  given  for  regeneration  to  take  place, 
stimulation  of  the  chorda  now  causes  a  constriction  in  the  vessels. 
The  experiment  can  also  be  reversed.  That  is,  by  suturing 
the  central  end  of  the  cervical  sympathetic  to  the  peripheral  end 
of  the  divided  lingual  the  fibers  of  the  former  grow  along  the  paths 
of  the  old  dilator  fibers,  and  after  regeneration  has  taken  place 
stimulation  of  the  sympathetic  causes  dilatation  of  the  blood- 
vessels in  the  gland.  These  results  are  particularly  instructive,  as 
vasoconstriction  is  an  example  of  the  excitatory  effect  of  the  nerve 
impulse,  being  the  result  of  a  contraction  of  the  circular  muscles 
in  the  vessels,  while  vasodilatation  is  an  example  of  inhibitory 
action,  being  due  to  an  inhibition  of  the  contraction  of  the  same 
muscles.  Yet  obviously  these  two  opposite  effects  are  determined 
not  by  the  nature  of  the  nerve  fibers,  but  by  their  place  or  mode 
of  ending  in  the  gland. 

Separation  of  the  Afferent  and  Efferent  Fibers  in  the  Roots 
of  the  Spinal  Nerves. — According  to  the  Bell-Magendie  discovery, 

*  Langley,  "Journal  of  Physiology,"  23,  240,  1898;  ibid.,  30,  439,  1904; 
"Proceedings  Royal  Society,"  73,  1904. 

6 


82          THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE. 

the  motor  fibers  to  the  voluntary  muscles  emerge  from  the  spinal 
cord  in  the  anterior  roots,  while  the  fibers  that  give  rise  to  sensa- 
tions enter  the  cord  through  the  posterior  roots.  These  facts  have 
been  demonstrated  beyond  all  doubt.  Magendie  discovered  an 
apparent  exception  in  the  phenomenon  of  recurrent  sensibility. 
When  the  anterior  root  is  severed  and  its  peripheral  end  is  stimu- 
lated only  motor  effects  should  be  obtained.  Magendie  observed, 
however,  upon  dogs  that  in  certain  cases  the  animals  showed  signs 
of  pain.  This  apparent  exception  to  the  general  rule  was  after- 
ward explained  satisfactorily.  It  was  shown  that  the  fibers  in 
question  do  not  really  belong  to  the  anterior  root, — that  is,  they  do 
not  emerge  from  the  cord  with  the  root  fibers;  they  are,  in  fact, 
sensory  fibers  for  the  meningeal  membranes  of  the  cord  which 
are  on  their  way  to  the  posterior  roots  and  which  enter  the  cord 
with  the  fibers  of  the  latter.  Since  the  work  of  Bell  and  Magendie 
it  has  been  a  question  whether  their  law  applies  to  all  afferent  and 
efferent  fibers  and  not  simply  to  the  motor  and  sensory  fibers  proper. 
The  experimental  evidence  upon  this  point,  as  far  as  the  mammals 
are  concerned,  has  accumulated  slowly.  Various  authors  have  shown 
that  stimulation  of  the  anterior  roots  of  certain  spinal  nerves  may 
cause  a  constriction  of  the  blood-vessels,  an  erection  of  the  hairs 
(stimulation  of  the  pilomotor  fibers),  a  secretion  of  sweat,  and  so 
on,  while  stimulation  of  the  posterior  roots  in  the  same  regions  is 
without  effect  upon  these  peripheral  tissues.  One  apparent  excep- 
tion, however,  has  been  noted.  A  number  of  observers  have  found 
that  stimulation  of  the  peripheral  end  of  the  divided  posterior 
roots  (fifth  lumbar  to  first  sacral)  causes  a  vascular  dilatation  in 
the  hind  limb.  The  matter  has  been  particularly  investigated  by 
Bayliss,*  who  gives  undoubted  proof  of  the  general  fact.  At  the 
same  time  he  shows  that  the  fibers  in  question  are  not  efferent 
fibers  from  the  cord  passing  out  by  the  posterior  instead  of  the  an- 
terior roots.  This  is  shown  by  the  fact  that  they  do  not  degenerate 
when  the  root  is  cut  between  the  ganglion  and  the  cord,  as  they 
should  do  if  they  originated  from  cells  in  the  cord.  Bayliss's  own 
explanation  of  this  curious  fact  is  that  the  fibers  in  question  are 
ordinary  afferent  fibers,  but  that  they  are  capable  of  a  double  ac- 
tion: they  can  convey  sensory  impulses  from  the  blood-vessels  to 
the  cord  according  to  the  usual  type  of  sensory  fibers,  but  they 
can  also  convey  efferent  impulses,  antidromic  impulses  as  he  desig- 
nates them,  to  the  muscles  of  the  blood-vessels.  In  other  words, 
for  this  special  set  of  fibers  he  attempts  to  re-establish  the  view 
held  by  physiologists  before  the  time  of  Bell, — namely,  that  one 
and  the  same  fiber  transmits  normally  both  afferent  and  efferent 
impulses.  An  exception  so  peculiar  as  this  to  an  otherwise  general 
rule  cannot  be  accepted  without  hesitation.  Some  facts  are  given 
*  Bayliss,  "Journal  of  Physiology,"  26,  173,  1901,  and  28,  276,  1902. 


THE    PHENOMENON    OF    CONDUCTION.  83 

on  p.  152  that  suggest  an  explanation  less  opposed  to  current 
views  than  that  offered  by  Bayliss. 

Cells  of  Origin  of  the  Anterior  and  Posterior  Root  Fibers. — 
The  efferent  fibers  of  the  anterior  root  arise  as  axons  or  axis  cylinder 
processes  from  nerve  cells  in  the  gray  matter  of  the  cord  at  or  near 
the  exit  of  the  root.  The  motor  fibers  to  the  voluntary  muscles 
arise  from  the  large  cells  of  the  anterior  horn  of  gray  matter;  the 
fibers  to  the  plain  muscle  and  glands,  autonomic  fibers  according 
to  Langley's  nomenclature,  take  their  origin  from  spindle-shaped 
nerve  cells  lying  in  the  so-called  lateral  horn  of  the  gray  matter.* 
According  to  the  accepted  belief  regarding  the  nutrition  of  nerve 
fibers,  any  section  or  lesion  involving  these  portions  of  the  gray  mat- 
ter or  the  anterior  root  will  be  followed  by  a  complete  degeneration 
of  the  efferent  fibers.  In  the  case  of  the  fibers  to  the  voluntary 
muscles  this  degeneration  will  extend  to  the  muscles  and  include 
the  end-plates.  In  the  case  of  the  autonomic  fibers  the  degenera- 
tion will  extend  to  the  peripheral  ganglia  in  which  they  terminate, 
involving,  therefore,  the  whole  extent  of  what  is  called  the  pre- 
ganglionic  fiber  (see  the  chapter  on  the  autonomic  nerves  and  the 
sympathetic  system).  The  posterior  root  fibers  have  their  origin 
in  the  nerve  cells  contained  in  the  posterior  root  ganglia.  These 
cells  are  unipolar,  the  single  process  given  off  being  an  axis  cylinder 
process  or  axon.  It  divides  into  two  branches,  one  passing  into 
the  cord  by  way  of  the  posterior  root,  the  other  toward  the  periph- 
eral tissues  in  the  corresponding  spinal  nerve  in  which  they  form  the 
peripheral  sensory  nerve  fibers.  It  follows  that  a  section  or  lesion 
of  the  posterior  root  will  result  in  a  degeneration  of  the  branch 
entering  the  cord,  this  branch  having  been  cut  off  from  its  nutri- 
tive relationship  with  its  cells  of  origin.  The  degeneration  will  in- 
volve the  entire  length  of  the  branch  and  its  collaterals  to  their 
terminations  among  the  dendrites  of  other  spinal  or  bulbar  neurons 
(see  the  chapter  on  the  spinal  cord).  After  a  lesion  of  this  sort 
the  stump  of  the  posterior  root  that  remains  in  connection  with 
the  posterior  root  ganglion  maintains  its  normal  structure.  On  the 
other  hand,  a  section  or  lesion  involving  the  spinal  nerve  will  be 
followed  by  a  degeneration  of  all  the  fibers,  efferent  and  afferent, 
lying  to  the  peripheral  side  of  the  lesion,  since  these  fibers  are  cut 
off  from  connection  with  their  cells  of  origin,  while  the  fibers  in  the 
central  stump  of  the  divided  nerve  will  retain  their  normal  structure. 

Afferent  and  Efferent  Fibers  in  the  Cranial  Nerves. — The 
first  and  second  cranial  nerves,  the  olfactory  and  the  optic,  contain 
only  afferent  fibers,  which  arise  in  the  former  nerve  from  the  olfac- 
tory epithelium  in  the  nasal  cavity,  in  the  latter  from  the  nerve 
cells  in  the  retina.  The  third,  fourth,  and  sixth  nerves  contain 
only  efferent  fibers  which  arise  from  the  nerve  cells  constituting 
*  Herring,  "Journal  of  Physiology,"  29,  282,  1903. 


84  THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 

their  nuclei  of  origin  in  the  midbrain  and  pons.  The  fifth  nerve 
resembles  the  spinal  nerves  in  that  it  has  two  roots,  one  containing 
afferent  and  the  other  efferent  fibers.  The  efferent  fibers,  consti- 
tuting the  small  root,  arise  from  nerve  cells  in  the  pons  and  mid- 
brain,  the  afferent  fibers  arise  from  the  nerve  cells  in  the  Gasserian 
ganglion.  This  ganglion,  being  a  sensory  ganglion,  is  constituted 
like  the  posterior  root  ganglia.  Its  nerve  cells  give  off  a  single 
process  which  divides  in  T,  one  branch  passing  into  the  brain  by  way 
of  the  large  root,  while  the  other  passes  to  the  peripheral  tissues  as  a 
sensory  fiber  of  the  fifth  nerve.  The  seventh  nerve  may  also  be 
homologized  with  a  spinal  nerve.  The  facial  nerve  proper  consists 
of  only  efferent  fibers,  which  arise  from  nerve  cells  constituting 
its  nucleus  of  origin  in  the  pons.  The  geniculate  ganglion,  attached 
to  this  nerve  shortly  after  its  emergence,  is  similar  in  structure  to 
the  Gasserian  or  a  posterior  root  ganglion.  Its  nerve  cells  send  off 
processes  which  divide  in  T  and  constitute  afferent  fibers  in  the 
so-called  nervus  intermedius  or  nerve  of  Wrisberg.  The  eighth 
nerve  consists  only  of  afferent  fibers  which  arise  from  the  nerve 
cells  in  the  spiral  ganglion  of  the  cochlea,  cochlear  branch,  and  from 
those  constituting  the  vestibular  or  Scarpa's  ganglion,  the  vestibu- 
lar  branch.  Both  of  these  ganglia  are  sensory,  resembling  the 
posterior  root  ganglia  in  structure.  The  ninth  nerve  is  also  mixed, 
the  efferent  fibers  arising  from  the  motor  nucleus  in  the  medulla, 
while  the  sensory  fibers  arise  in  the  superior  and  petrosal  ganglia 
found  on  the  nerve  at  its  emergence  from  the  skull.  The  tenth  is  a 
mixed  nerve,  its  efferent  fibers  arising  in  motor  nuclei  in  the  me- 
dulla, the  afferent  fibers  in  the  nerve  cells  of  the  ganglia  lying  upon 
the  trunk  of  the  nerve  at  its  exit  from  the  skull  (ganglion  jugulare 
and  nodosum).  The  eleventh  and  twelfth  cranial  nerves  contain 
only  efferent  fibers  that  arise  from  motor  nuclei  in  the  medulla. 

It  will  be  seen  from  these  brief  statements  that  in  all  the  nerve 
trunks  of  the  central  nervous  system — that  is,  the  spinal  and  the 
cranial  nerves — the  cells  of  origin  of  the  efferent  fibers  lie  within 
the  gray  matter  of  the  brain  or  cord,  while  the  cells  of  origin  of  the 
afferent  fibers  lie  in  sensory  ganglia  outside  the  central  nervous 
system, — namely,  in  the  posterior  root  ganglia  for  the  spinai 
nerves,  in  the  ganglion  semilunare  (Gasseri),  the  g.  geniculi,  the 
g.  spirale,  the  g.  vestibulare,  the  g.  superius  and  g.  petrosum  of  the 
glossopharyngeal,  and  the  g.  jugulare  and  g.  nodosum  of  the  vagus. 
These  various  sensory  ganglia  attached  to  the  cranial  nerves  corre- 
spond essentially  in  their  structure  and  physiology  with  the  posterior 
root  ganglia  of  the  spinal  nerves. 

Independent  Irritability  of  Nerve  Fibers. — Although  the 
nerve  fibers  under  normal  conditions  are  stimulated  only  at  their 
ends,  the  efferent  fibers  at  the  central  end,  the  afferent  at  the 
peripheral  end,  yet  any  nerve  fiber  may  be  stimulated  by  artificial 


THE    PHENOMENON    OF    CONDUCTION.  85 

means  at  any  poirit  in  its  course.  Artificial  stimuli  capable  of 
affecting  the  nerve  fiber — that  is,  capable  of  generating  in  it  a  nerve 
impulse  which  then  propagates  itself  along  the  fiber — may  be  divided 
into  the  following  groups : 

1.  Chemical  stimuli.     Various  chemical  reagents,  when  applied 
directly  to  a  nerve  trunk,  excite  the  nerve  fibers.    Such  reagents 
are  concentrated  solutions  of  the  neutral  salts  of  the  alkalies,  acids, 
alkalies,  glycerin,  etc.   This  method  of  stimulation  is  not,  however, 
of  much  practical  value  in  experimental  work,  since  it  is  difficult  or 
impossible  to  control  the  reaction. 

2.  Mechanical  stimuli.    A'blow  or  pressure  or  a  mechanical  in- 
jury of  any  kind  applied  to  a  nerve  trunk  also  excites  the  fibers. 
This  method  of  stimulating  the  fibers  is  also  difficult  to  control 
and  has  had,  therefore,  a  limited  application  in  experimental  work. 
The  mechanical  stimulus  is  essentially  a  pressure  stimulus,  and  the 
difficulty  lies  in  controlling  this  pressure  so  that  it  shall  not  actually 
destroy  the  nerve  fiber  by  rupturing  the  delicate  axis  cylinder. 
Various  instruments  have  been  devised  by  means  of  which  light 
blows  may  be  given  to  the  nerve,  sufficient  to  arouse  an  impulse, 
but  insufficient  to  permanently  injure  the  fibers.    The  results  ob- 
tained by  this  method  have  been  very  valuable  in  physiology  as  con- 
trols for  the  experiments  made  by  the  usual  method  of  electrical 
stimulation.    It  may  be  mentioned  also  that  under  certain  condi- 
tions— for  instance,  at  one  stage  in  the  regeneration  of  injured 
nerve  fibers   mechanical  stimuli  may  be   more  effective  than 
electrical,  that  is,  may  stimulate  the  nerve  fiber  when  electrical 
stimuli  totally  fail  to  do  so. 

3.  Thermal  stimuli.    A  sudden   change   in  temperature  may 
stimulate  the  nerve  fibers.    This  method  of  stimulation  is  very 
ineffective  for  motor  fibers,  only  very  extreme  and  sudden  changes, 
such  as  may  be  obtained  by  applying  a  heated  wire  directly  to 
the  nerve  trunk,  are  capable  of  so  stimulating  them  as  to  produce 
a  muscular  contraction.     On  the  other  hand,  the  sensory  nerve 
fibers  are  quite  sensitive  to  changes  of  temperature.    If  a  nerve 
trunk  in  a  man  or  animal  is  suddenly  cooled,  or  especially  if  it  is 
suddenly  heated  to  60°  to  70°  C.,  violent  pain  results  from  the 
stimulation  of  the  sensory  fibers  in  the  trunk,  while  the  motor 
fibers  are  apparently  not  acted  upon.    We  have  in  this  fact  one 
of  several  differences  in  reaction  between  motor  and  sensory  fibers 
which  have  been  noted  from  time  to  time,  and  which  seem  to 
indicate  that  there  is  some  difference  in  structure  or  irritability 
between  them. 

4.  Electrical  stimuli.    Some  form  of  the  electrical  current  is  be- 
yond question  the  most  effective  and  convenient  means  of  stimulat- 
ing nerve  fibers.    We  may  employ  either  the  galvanic  current — that 
is,  the  current  taken  directly  from  a  battery — or  the  induced  current 


86 


THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 


from  the  secondary  coil  of  an  induction  apparatus  or  the  so-called 
static  electricity  from  a  Ley  den  jar  or  other  source.  In  most  experi- 
mental work  the  induced  current  is  used.  The  terminal  wires  from 
the  secondary  coil  are  connected  usually  with  platinum  wires  im- 
bedded in  hard  rubber,  forming  what  is  known  as  a  stimulating  elec- 
trode. (See  Fig.  29.)  By  this  means  the  platinum  ends  which  now 


Fig.  29.— Stimulating  (catheter)  electrodes  for  nerves:  6,  Binding  posts  for  attachment 
of  wires  from  the  secondary  coil;  «,  insulating  sheath  of  hard  rubber;  p,  platinum  points 
laid  upon  the  nerve. 

form  the  electrodes,  anode  and  cathode,  can  be  placed  close  together 
upon  the  nerve  trunk,  and  the  induced  current  passing  from  one  to 
the  other  through  a  short  stretch  of  the  nerve  sets  up  at  that  point 
nerve  impulses  which  then  propagate  themselves  along  the  nerve 
fibers.  The  induction  current  is  convenient  because  of  its  intensity, 
which  overcomes  the  great  resistance  offered  by  the  moist  tissue ;  be- 
cause of  its  very  brief  duration,  in  consequence  of  which  it  acts  as  a 
sharp,  quick,  single  stimulus  or  shock,  and  because  of  the  great  ease 
with  which  it  may  be  varied  as  to  rate  and  as  to  intensity.  On 
account  of  the  very  brief  duration  of  the  induced  current  it  is  dif- 
ficult to  distinguish  between  the  effects  of  its  opening  and  closing. 
The  Stimulation  of  the  Nerve  by  the  Galvanic  Current.— When 

however,  we  employ  the  galvanic 
current,  taken  directly  from  a  bat- 
tery, as  a  stimulus,  we  can,  of 
course,  allow  the  current  to  pass 
through  the  nerve  as  long  as  we 
please  and  can  thus  study  the  effect 
of  the  closing  of  the  current  as 
distinguished  from  that  of  the  open- 
ing, or  the  effect  of  duration  or 
direction  of  the  current,  etc. 

Du  Bois-Reymond' s  Law  of  Stim- 
ulation.— When  a  galvanic  current 
is  led  into  a  motor  nerve  it  is 
found,  as  a  rule,  that  with  all 
moderate  strengths  of  currents  there 
is  a  stimulus  to  the  nerve  at  the 
moment  it  is  closed,  the  making  or 
closing  stimulus,  and  another  when 
the  current  is  broken,  the  breaking 
or  opening  stimulus,  while  during 
the  passage  of  the  current  through  the  nerve  no  stimulation  takes 


Fig.  30. — Schema  of  the  arrange- 
ment of  apparatus  for  stimulating  the 
nerve  by  a  galvanic  current :_  6,  The 
battery;  k,  the  key  for  opening  and 
closing  the  circuit ;  c,  the  commutator 
for  reversing  the  direction  of  the  cur- 
rent; +  the  anode  or  positive  pole; 
—  the  cathode  or  negative  pole. 


THE  PHENOMENON  OF  CONDUCTION.  87 

place:  the  muscle  remains  relaxed.  We  may  express  this  fact 
by  saying  that  the  motor  nerve  fibers  are  stimulated  by  the  mak- 
ing and  the  breaking  of  the  current  or  by  any  sudden  change 
in  its  intensity,  but  remain  unstimulated  during  the  passage  of  cur- 
rents whose  intensity  does  not  vary. 

The  Anodal  and  Cathodal  Stimuli. — It  has  been  shown  quite  con- 
clusively that  the  nerve  impulse  started  by  the  making  of  the  current 
arises  at  the  cathode,  while  that  at  the  breaking  of  the  current 
begins  at  the  anode,  or,  in  other  words,  the  making  shock  or 
stimulus  is  cathodal,  while  tfce  breaking  stimulus  is  anodal.  This 
fact  is  true  for  muscle  as  well  as  nerve,  and  possibly  for  all  irritable 
tissues  capable  of  stimulation  by  the  galvanic  current.  This 
important  generalization  may  be  demonstrated  for  motor  nerves 
by  separating  the  anode  and  cathode  as  far  as  possible  and  re- 
cording the  latent  period  for  the  contractions  caused  respect- 
ively by  the  making  and  the  breaking  of  the  current  in  the  nerve. 
If  the  cathode  is  nearer  to  the  muscle  the  latent  period  of  the  mak- 
ing contraction  of  the  muscle  will  be  shorter  than  that  of  the  break- 
ing contraction  by  a  time  equal  to  that  necessary  for  a  nerve  impulse 
to  travel  the  distance  between  anode  and  cathode.  If  the  position 
of  the  electrodes  is  reversed  the  latent  period  of  the  making  con- 
traction will  be  correspondingly  longer  than  that  of  the  breaking 
contraction.  It  is  very  evident  from  these  facts  that  when  a 
current  is  passed  into  a  nerve  or  muscle  the  changes  at  the  two 
poles  are  different,  as  shown  by  the  differences  in  reactions  and 
properties  of  the  nerve  at  these  points.  Bethe  has  shown  that  a 
difference  may  be  demonstrated  even  by  histological  means.  After 
the  passage  of  a  current  through  a  nerve  for  some  time  the  axis 
cylinders  stain  more  deeply  than  normal  at  the  cathode  with  cer- 
tain dyes  (toluidin  blue),  while  at  the  anode  they  stain  less  deeply. 

Electrotonus. — The  altered  physiological  condition  of  the  nerve 
at  the  poles  during  the  passage  of  the  galvanic  current  is  designated 
as  electrotonus,  the  condition  round  the  anode  being  known  as 
anelectrotonus,  that  round  the  cathode  as  catelectrotonus.  Elec- 
trotonus expresses  itself  as  a  change  in  the  electrical  condition  of 
the  nerve  which  gives  rise  to  currents  known  as  the  electrotonic 
currents, — a  brief  description  of  these  currents  will  be  given  in 
the  next  chapter, — and  also  by  a  change  in  irritability  and  con- 
ductivity. The  latter  changes  were  first  carefully  investigated 
by  Pfliiger,  who  showed  that  when  the  galvanic  current,  or,  as  it  is 
usually  called  in  this  connection,  the  polarizing  current,  is  not  too 
strong  there  is  an  increase  in  irritability  and  conductivity  in  the 
neighborhood  of  the  cathode,  the  so-called  catelectrotonic  increase 
of  irritability,  while  in  the  region  of  the  anode  there  is  an  anelec- 
trotonic  decrease  in  irritability  and  conductivity.  These  opposite 
variations  in  the  state  of  the  nerve  are  represented  in  the  accom- 


88          THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE. 

panying  diagram.  Between  the  two  poles — that  is,  in  the  intrapolar 
region — there  is,  of  course,  an  indifferent  point,  on  one  side  of  which 
the  irritability  of  the  nerve  is  above  normal  and  on  the  other  side 
below  normal.  The  position  of  this  indifferent  point  shifts  toward 
the  cathode  as  the  strength  of  the  polarizing  current  is  increased. 
In  other  words,  as  the  current  increases  the  anelectrotonus  spreads 
more  rapidly  and  becomes  more  intense,  and  the  conductivity  in 
this  region  soon  becomes  so  depressed  as  to  block  entirely  the 
passage  of  a  nerve  impulse  through  it.  The  changes  on  the  cathodal 
side  are  not  so  constant  nor  so  distinct.  It  has  been  shown,* 
in  fact,  that  if  the  polarizing  current  is  continued  for  some  time, 
the  heightened  irritability  at  the  cathode  soon  diminishes  and 
sinks  below  normal,  so  that  in  fact  at  the  cathode  as  well  as  at 
the  anode  the  irritability  may  be  lost  entirely.  If  the  polarizing 
current  is  very  strong  this  depressed  irritability  at  the  cathode 
comes  on  practically  at  once.  Moreover,  when  a  strong  current 
that  has  been  passing  through  a  nerve  is  broken  the  condition  of 
depressed  irritability  at  the  cathode  persists  for  some  time  after 
the  opening  of  the  current. 

Pfliiger's  Law  of  Stimulation. — It  was  said  above  that  when 
a  galvanic  current  is  passed  into  a  nerve  there  is  a  stimulus  (catho- 
dal) at  the  making  of  the  current  and  another  stimulus  (anodal) 


Fig.  31. — Electrotonic  alterations  of  irritability  caused  by  weak,  medium,  and  strong 
battery  currents:  A  and  B  indicate  the  points  of  application  of  the  electrodes  to  the  nerve,  A 
being  the  anode,  B  the  cathode.  The  horizontal  line  represents  the  nerve  at  normal  irri- 
tability; the  curved  lines  illustrate  how  the  irritability  is  altered  at  different  parts  of  the 
nerve  with  currents  of  different  strengths.  Curve  j/1  shows  the  effect  of  a  weak  current,  the 
part  below  the  line  indicating  decreased,  and  that  above  the  line  increased  irritability;  at  x1 
the  curve  crosses  the  line,  this  being  the  indifferent  point  at  which  the  catelectrotonic  effects 
are  compensated  for  by  anelectrotonic  effects;  y'2  gives  the  effect  of  a  stronger  current,  and 
Vs,  of  a  still  stronger  current.  a  As  the  strength  of  the  current  is  increased  the  effect  becomes 
greater  and  extends  farther  into  the  extrapolar  regions.  In  the  intrapolar  region  the  in- 
different point  is  seen  to  advance,  with  increasing  strengths  of  current,  from  the  anode 
toward  the  cathode. — (Lombard.) 

at  the  breaking  of  the  current.  This  statement  is  true,  however, 
only  for  a  certain  range  of  currents.  Of  the  two  stimuli,  the  making 
or  cathodal  stimulus  is  the  stronger,  and  it  follows,  therefore, 

*  Werigo,  "  Pfliiger's  Archiv,"  84,  547,  1901.  See  Biedermann,  "  Elec- 
trophysiology,"  translated  by  Welby,  vol.  ii,  p.  140. 


THE  PHENOMENON  OF  CONDUCTION.  89 

that  when  the  strength  of  the  current  is  diminished  there  will  come 
a  certain  point  at  which  the  anodal  stimulus  will  drop  out.  With 
weak  currents  there  is  then  a  stimulus  only  at  the  make.  On  the 
other  hand,  when  very  strong  currents  are  used  the  stimuli  that  act 
at  the  two  poles  set  up  nerve  impulses  whose  passage  to  the  muscle 
may  be  blocked  by  the  depressed  conductivity  caused  by  the  electro- 
tonic  changes.  Whether  or  not  the  stimulus  will  be  effective  in 
causing  a  contraction  in  the  attached  muscle  will  depend  naturally 
on  the  relative  positions  of  the  electrodes, — that  is,  on  the  direction 
of  the  current  in  the  nerve.  In  describing  the  effect  of  these  strong 
currents  we  must  distinguish  between  what  are  called  ascending 
and  descending  currents.  Ascending  currents  are  those  in  which 
the  direction  of  the  current  in  the  nerve  is  away  from  the  muscle, 
a  position  of  the  poles,  therefore,  in  which  the  anode  is  closer  to 
the  muscle.  In  descending  currents  the  positions  are  reversed. 
Pfliiger's  law  of  contraction  or  of  stimulation  takes  account  of 
the  effect  of  extreme  variations  in  the  strength  of  the  current 
and  is  usually  expressed  in  tabular  form  as  follows:  The  letter  C 
indicates  that  the  nerve  is  stimulated  and  causes  a  contraction  in 
the  attached  muscle,  and  O  indicates  a  failure  in  the  stimulation 
(weak  currents)  or  a  failure  in  the  nerve  impulse  to  reach  the  muscle 
owing  to  blocking  (strong  currents) . 


Fig.  32.  Fig.  33. 

Figs.  32  and  33. — Schema  to  show  the  arrangement  of  apparatus  for  an  ascending  and  a 
descending  current:   Fig.  32,  ascending;   Fig.  33,  descending. 

ASCENDING  CURRENT.     DESCENDING  CTJRRKNT. 
Making.     Breaking.  Making.     Breaking. 

Very  weak  currents  . .  C  O  C  O 

Moderate         "     ....C  C  C  C 

Very  strong     "      O  C  C  O 

The  effects  obtained  with  the  strong  currents  are  readily  under- 
stood if  we  bear  in  mind  the  facts  stated  above  regarding  electro- 
tonus.  When  the  current  is  ascending  the  stimulus  on  making 
starts  from  the  cathode,  but  cannot  reach  the  muscle  because  it 
is  blocked  by  a  region  of  anelectrotonus  in  which  the  conduc- 


90  THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 

tivity  is  depressed.  The  stimulus  on  breaking  takes  place  at 
the  anode  and  the  impulse  encounters  no  resistance  in  its  passage 
to  the  muscle.  With  the  descending  current  the  cathode  lies  next 
to  the  muscle  and  the  making  or  cathodal  stimulus  of  course  causes 
a  contraction.  On  breaking,  however,  the  impulse  that  is  started 
from  the  anode  is  blocked  by  the  depressed  irritability  in  the 
cathodal  region,  which,  as  has  been  said,  comes  on  promptly  with 
strong  currents  and  persists  for  a  time  after  the  current  is  broken. 

The  Opening  and  the  Closing  Tetanus.— While  the  du  Bois-Reymond 
law  stated  above  expresses  the  facts  as  usually  observed  upon  a  nerve-muscle 
preparation,  there  are  a  number  of  observations  which  indicate  that  the 
excitation  at  the  anode  and  the  cathode  during  the  passage  of  a  current 
may  give  rise  to  a  series  of  stimuli  instead  of  a  single  stimulus.  Thus  with 
sensory  nerves  it  is  well  known  that  the  stimulation,  as  judged  by  the 
sensations  aroused,  continues  while  the  current  is  passing  instead  of  being 
limited  to  the  moment  of  making  or  of  breaking  of  the  current.  In  this 
respect,  as  in  stimulation  by  high  temperatures,  the  sensory  fibers  differ 
apparently  from  the  motor.  When  a  galvanic  current  is  passed  through  the 
ulnar  nerve  at  the  elbow  sensations  are  felt  during  the  entire  time  of  passage 
of  the  current.  But  in  an  ordinary  nerve-muscle  preparation  it  is  also  fre- 
quently observed  that  at  the  moment  of  opening  the  current  a  tetanic  con- 
traction, persisting  for  some  time,  is  obtained  instead  of  a  single  twitch.  This 
phenomenon  is  known  as  the  opening  tetanus  or  Hitter's  tetanus,  and  Pfliiger 
has  shown  that  the  continuous  excitation  proceeds  from  the  anode,  since 
in  the  case  of  a  descending  current  division  of  the  nerve  in  the  intrapolar 
region  brings  the  muscle  to  rest.  In  the  same  way  it  frequently  happens 
that  upon  closing  the  current  through  a  nerve  the  muscle,  instead  of  giving  a 
twitch,  goes  into  a  persistent  tetanic  contraction.  The  tetanus  in  this  case 
is  designated  as  the  closing  or  Pflii^er's  tetanus.  Both  of  these  phenomena 
are  observed,  especially,  when  the  irritability  of  the  nerve  is  for  any  reason 
greater  than  normal.  It  should  be  added  that  the  opening  and  the  closing 
tetanus  may  be  observed  also  in  a  muscle  when  the  galvanic  current  is  passed 
through  it. 

Stimulation  of  the  Nerves  in  Man. — For  therapeutic  as  well 
as  diagnostic  and  experimental  purposes  it  often  becomes  desirable 
to  stimulate  the  nerves,  particularly  the  motor  nerves,  in  man. 
We  may  use  for  this  purpose  either  the  induced  (faradic,  alternat- 
ing) current  or  the  direct  battery  current  (galvanic  or  continuous 
current).  In  such  cases  the  electrodes  cannot  be  applied,  of  course, 
directly  to  the  nerve;  it  becomes  necessary  to  stimulate  through 
the  skin,  and  the  so-called  unipolar  method  is  employed.  The 
unipolar  method  consists  in  placing  one  electrode,  the  active  or 
stimulating  electrode,  over  the  nerve  at  the  point  which  it  is  desired 
to  stimulate,  while  the  other  electrode,  the  inactive  or  indifferent 
electrode,  is  applied  to  the  skin  at  some  more  or  less  remote  part, 
usually  at  the  back  of  the  neck.  The  indifferent  electrode  is  made 
large  enough  to  cover  several  square  centimeters  of  the  skin,  and  one 
may  conceive  the  threads  of  current  as  passing  from  it  into  the 
moist  tissues  of  the  body,  and  thence  to  the  active  electrode.  As 
the  threads  of  current  condense  to  this  latter  electrode  they  pass 
through  the  motor  nerve  which  lies  under  it,  and  if  sufficiently  in- 


THE    PHENOMENON    OF    CONDUCTION. 


91 


tense,  will  stimulate  the  nerve.  The  arrangement  is  represented  in 
the  accompanying  schema  (Fig.  34),  showing  the  disposition  of  the 
electrodes  for  stimulating  the  median  nerve.  At  the  indifferent 
electrode  the  sensory  nerves  of  the  skin  are  of  course  stimulated,  but 
no  motor  response  is  obtained,  as  no  motor  nerve  lies  immediately 
under  the  skin.  Moreover,  the  large  size  of  this  electrode  tends  to 
diffuse  the  current  and  thus  reduce  its  effectiveness  in  stimulating. 
The  active  or  stimulating  electrode  is  small  in  size,  particularly 
when  induction  currents  are  employed,  so  that  the  current  may  be 
condensed  and  thus  gain  in  effectiveness.  The  dry  surface  of  the 
skin  is  a  poor  conductor  of  the  electrical  current,  and  to  reduce  the 
resistance  at  the  points  at  which  the  electrodes  come  in  contact 


_  Fig.  34. — Schema  to  show  the  unipolar  method  of  stimulation  in  man.  The  anode, 
+ ,  is  represented  as  the  stimulating  pole,  applied  over  the  median  nerve.  The  cathode. 
— ,  is  the  indifferent  pole. 

with  the  skin  each  is  covered  with  cotton  or  chamois  skin  kept 
moistened  with  a  dilute  saline  solution. 

Motor  Points. — By  means  of  the  unipolar  method  nearly  every 
voluntary  muscle  of  the  body  may  be  stimulated  separately.  All 
that  is  necessary,  when  the  induced  current  is  used,  is  to  bring  the 
active  electrode  as  nearly  as  possible  over  the  spot  at  which  the 
muscle  receives  its  motor  branch.  A  diagram  showing  these  motor 
points  for  the  arm  is  given  in  Fig.  35.  In  the  same  way  the 


92 


THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 


nerves  of  the  brachial  plexus  and  other  nerve  trunks  may  be 
stimulated  very  readily  through  the  skin.  When  the  induction 
current  is  used  no  distinction  is  made  between  the  cathodic  and 
anodic  effects.  When,  however,  the  battery  current  is  employed 


.  tr!«p.  «aput 
longuml 


ML  flexor  carpi  ulnari 


M.  flex,  digitor.  nub 
lim.  (digit!  II  el  111) 


M.  palmarts  l>rev. 
M.  abductor  digit  i 

It.  flexor  digit,  roin. 
M.  opponcns  digit. 


M.  flex.  poll.  brcv. 

M.  adductor  polite  bre». 


Fig.  35. — Motor  points  in  upper  extremity. 

one  may  make  the  stimulating  electrode  either  anode  or  cathode, 
and  under  these  circumstances  a  marked  difference  is  observed 
in  the  strength  of  the  current  that  it  is  necessary  to  use  to 
get  a  response.  With  the  battery  or  galvanic  current,  in  fact, 
one  may  distinguish  four  stimuli,  the  closing  and  the  open- 
ing shock  when  the  stimulating  electrode  is  cathode  and  the 
closing  and  the  opening  shock  when  it  is  anode.  The  con- 
tractions resulting  from  these  four  stimuli  are  designated  usually 
as  follows:  The  cathodol  closing  contraction,  C  C  C;  the  cathodal 
opening  contraction,  COG;  the  anodal  closing  contraction, 
A  C  C;  and  the  anodal  opening  contraction,  A  O  C.  If  the  minimal 
amount  of  current  necessary  to  give  each  of  these  contractions 
is  measured  in  milliamperes  by  means  of  a  suitable  ammeter, 


THE    PHENOMENON    OF    CONDUCTION.  93 

it  will  be  found  that  the  four  stimuli  are  of  different  efficiencies. 
The  usual  relationship  is  expressed  by  the  sequence  C  C  C  > 
ACC  >AOC  >C  O  C,  although  this  sequence  is  subject  to  some 
individual  variation.  Pathological  or  traumatic  lesions  that 
cause  the  degeneration  of  the  nerves  may  be  revealed  by  the  use 
of  these  methods  of  stimulation.  The  nerve  trunk  under  such 
circumstances  fails  to  respond  to  either  form  of  stimulus,  in- 
duced or  galvanic.  The  muscle,  on  the  other  hand,  while  it  may 
fail  to  respond  to  induction  shocks,  is  stimulated  by  the  gal- 
vanic current,  and,  indeed,  may  show  an  increased  irritability 
toward  this  form  of  stimulus,  although  the  contractions  are 
more  sluggish  in  character  tnan  in  a  muscle  with  a  normal  nerve 
supply.  Certain  qualitative  changes  in  the  reaction  of  the 
muscle  to  the  galvanic  current  may  also  be  noticed,  for  instance, 
the  A  C  C  is  sometimes  obtained  with  less  current  than  the  C  C  C. 
This  qualitative  and  quantitative  change  in  reaction  to  the 
galvanic  current,  and  the  loss  of  irritability  to  the  induced  cur- 
rent, constitute  what  is  known  as  the  reaction  of  degeneration. 


Fig.  36. — Two  schemata  to  show  the  relation  between  the  physical  and  the  physio- 
logical electrodes  or  poles.  Each  schema  represents  the  forearm  with  the  median  nerve, 
M.  In  /  the  stimulating  electrode  is  the  cathode ;  the  threads  of  current  which  have  started 
from  the  anode  (the  indifferent  electrode)  placed  elsewhere,  converge  to  this  pole.  Where 
these  threads  enter  the  nerve  we  have  a  series  of  physiological  anodes,  a;  where  they  leave, 
a  series  of  physiological  cathodes,  c.  In  //  the  stimulating  electrode  is  the  anode.  The 
threads  of  current  leave  this  pole  to  traverse  the  body  toward  the  indifferent  electrode 
(cathode).  Where  they  enter  and  leave  the  nerve  we  have,  as  in  the  first  case,  physio- 
logical anodes  and  cathodes,  now,  however,  on  the  opposite  sides  of  the  nerve. 


Distinction  between  Physical  and  Physiological  Poles. — The 

facts  stated  above  seem  to  show,  at  first  sight,  that  by  the 
unipolar  method  we  may  obtain  both  an  opening  and  a  closing 
shock  at  either  the  cathode  or  anode, — a  result  which  is  ID 
apparent  contradiction  to  the  general  law  that  the  making  or 
closing  stimulus  occurs  only  at  the  cathode  and  the  breaking 
or  opening  stimulus  only  at  the  anode.  This  apparent  contra- 
diction is  readily  explained  when  we  remember  that  in  the 


94          THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE. 

unipolar  method  the  active  electrode  rests  upon  the  skin  over  the 
nerve,  and  that  the  threads  of  current  radiating  from  this  point 
enter  the  nerve  at  one  point  and  leave  it  at  another.  Evidently, 
therefore,  so  far  as  the  nerve  is  concerned,  there  will  be  an  anode 
where  the  current  is  considered  as  entering  the  nerve  and  a  cathode 
where  it  leaves  it,  so  that  under  the  active  electrode,  whether  this 
is  physically  an  anode  or  cathode,  there  will  be,  as  regards  the 
nerve,  a  series  of  what  may  be  called  physiological  cathodes  and 
anodes.  The  closing  shock  arises  at  these  cathodes,  the  opening 
shock  at  the  anodes.  The  position  of  the  series  of  anodes  and 
cathodes  will  vary  according  as  the  active  electrode  is  an  anode 
or  cathode,  as  is  indicated  in  the  accompanying  diagram  (Fig.  36). 


CHAPTER  IV. 

THE  ELECTRICAL  PHENOMENA  SHOWN  BY  NERVE 
AND  MUSCLE. 

The  Demarcation  Current — Our  definite  knowledge  of  the 
electrical  properties  of  living  tissue  began  with  the  celebrated  in- 
vestigations of  du  Bois-Reymond*  (1843).  When  a  muscle  or 
nerve  is  removed  from  the  body,  and,  in  the  case  of  the  muscle, 
when  one  tendinous  end  is  cut  off,  it  is  found  that  the  cut  end  has 
an  electrical  potential  differing  from  that  of  the  uninjured  longi- 
tudinal surface  of  the  preparation.  Following  the  usual  nomen- 
clature, the  cut  end  is  electronegative,  the  longitudinal  surface 
is  electropositive.  If,  therefore,  the  longitudinal  surface  is  con- 
nected by  a  conductor  with  the  cut  surface  a  current  will  flow  from 
the  former  to  the  latter,  as  is  indicated  in  -the  accompanying  dia- 
gram. 


Fig.  37. — Schema  showing  the  course  of  the  demarcation  current  in  an  excised  nerve, 
when  a  point  on  the  longitudinal  and  one  on  the  cut  surface  are  united  by  a  conductor. 

While  the  direction  of  the  current  through  the  conductor  con- 
necting the  two  points  is  from  the  longitudinal  to  the  cut  surface 
the  current  may  be  considered  as  being  completed  in  the  opposite 
direction  within  the  substance  of  the  muscle  or  nerve,  as  shown 
in  the  diagram.  We  may,  in  fact,  consider  an  excised  nerve  or 
muscle  as  a  battery,  the  cut  end  representing  the  zinc  plate  and 
the  longitudinal  surface  the  copper  plate.  Within  the  battery 
the  direction  of  the  current  is  from  zinc  to  copper,  from  cut  end 
to  longitudinal  surface;  outside  the  battery  the  direction  is  from 
copper  to  zinc,  from  longitudinal  to  cut  surface.  If  two  wires 
are  connected  with  the  muscle  or  nerve  the  end  of  the  one  attached 
to  the  longitudinal  surface  will  represent  the  positive  pole  or  anode, 
the  end  of  the  one  attached  to  the  cut  end  will  represent  the  cathode 

*  "Untersuchungen  iiber  thierische  Elektricitat,"  du  Bois-Reymond, 
1848-1860. 

95 


96 


THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 


or  negative  pole.     On  joining  the  ends  of  the  wires  a  current  will 
pass  from  positive  to  negative  pole. 

A  current  of  this  character  from  an  excised  nerve  or  muscle 
is,  of  course,  small  in  amount  and  to  detect  it  one  must  make 
use  of  a  delicate  electrometer  of  some  sort  (see  below).  Du  Bois- 
Reymond  considered  that  the  difference  in  electrical  potential 
which  gives  rise  to  this  current  exists  normally  in  the  muscle, 
although  masked  by  an  opposite  condition  in  the  tendinous  ends, 
and  he  therefore  spoke  of  the  currents  as  the  natural  muscle  or 
natural  nerve  currents.  It  has  since  been  shown  by  Hermann 

that  this  view  is  incorrect;  that  the 
perfectly  normal  uninjured  muscle  or 
nerve  has  the  same  electrical  potential 
throughout  and  will  therefore  give  no 
current  when  any  two  points  are  con- 
nected by  a  conductor.  Moreover,  the 
completely  dead  muscle  or  nerve  shows 
no  current.  The  difference  in  poten- 
tial that  is  found  in  the  excised 
nerve  or  muscle  is  due,  according  to 
Hermann,  to  the  fact  that  at  the  cut 
end  the  nerve  or  muscle  is  injured.  The 
chemical  changes  that  take  place  as  a 
result  of  the  injury  make  the  tissue 
electronegative  as  regards  the  un- 
changed living  substance  elsewhere. 
For  this  reason  Hermann  described 
the  current  as  a  demarcation  current; 
others  have  called  it  the  current  of 
injury. 

The  nature  of  the  changes  at  the  injured  end  are  not  known.  It  is  int-r- 
estmg  to  note  that  Bernstein  *  has  shown  that  the  electromotive  force  of  the 
muscle  current  increases  with  the  temperature,  a  fact  which  leads  him  to 
conclude  that  the  difference  in  potential  between  the  longitudinal  and  cut 
surface  of  the  muscle  depends  upon  a  difference  in  concentration-  of  the 
electrolytes.  The  muscle,  in  fact,  acts  after  the  manner  of  a  "concentration 
cell.  Such  a  difference  in  concentration  may  pre-exist  in  the  normal  mus- 
cle, or,  according  to  the  view  adopted  above,  is  developed  as  the  result  of 
injuring  one  end  of  the  muscle.  It  may  be  supposed  that  the  injury  causes 
changes  which  result  in  the  formation  of  new  organic  or  inorganic  electro- 
lytes and  thus  increases  the  concentration  at  that  point.  From  what  is 
known  of  the  chemical  changes  in  muscle  it  is  safe  to  assert  that  there  is  an 
increased  production  of  lactic  acid  at  the  injured  end,  and  it  is  probable 
that  other  electrolytes  may  be  liberated  in  diffusible  form.  With  this  increased 
concentration  at  the  injured  area  a  development  of  electric  potential  might 
be  expected,  owing  to  the  probability  that  the  cations  (H,  K,  Na,  Mg,  Ca) 
will  diffuse  off  more  rapidly  and  thus  leave  the  injured  end  with  a  negative 
charge.  Experiments  made  by  Urano  and  von  Frey  on  muscle  juice  squeezed 
out  of  the  muscle  fibers  under  high  pressure  have  shown  that  when  it  is  diffused 
against  sugar  solutions  it  loses  its  K  and  Mg  more  rapidly  than  the  PO4  and  SO4. 
*  "Pfliiger's  Archiv,"  1902,  92,  521. 


Fig.  38.  —  Schema  showing 
the  principle  of  construction  of 
the  galvanometer:  M,  The  mag- 
net suspended  by  a  thread:  S, 
the  battery,  with  the  wires  lead- 
ing off  the  current  encircling  the 
magnet. 


ELECTRICAL    PHENOMENA.  97 

Means  of  Demonstrating  the  Muscle  Current. — The  demarcation 
current  and  other  electrical  conditions  to  be  described  require  especial  appara- 
tus for  their  study.  To  detect  the  existence  of  a  current  physiologists  use 
either  a  galvanometer  or  a  capillary  electrometer.  The  galvanometers  employed 
are  of  several  types,  the  Kelvin  reflecting  galvanometer,  the  d'Arsonval  form, 
and  more  recently  the  "string-galvanometer"  of  Einthoven.  The  principle 
of  the  galvanometer  lies  in  the  fact  that  a  magnetic  needle  is  deflected  when 
an  electrical  current  passes  through  a  wire  in  its  vicinity.  If  a  magnetic 
needle  is  swung  by  a  delicate  thread  so  as  to  move  easily,  it  will  come  to  rest 
in  the  magnetic  meridian  with  its  north  pole  pointing  north.  If  now  a  wire  is 
curved  round  it,  as  shown  in  the  accompanying  diagram  (Fig.  38),  and  a  battery 
current  is  sent  through  this  wire,  the  needle  will  be  deflected  to  the  right  if  the 
current  passes  in  one  direction  and  to  the  left  if  it  passes  in  the  opposite  direc- 
tion. The  movement  of  the  needle  is  an  indication  of  the  presence  and 
direction  of  the  electrical  current  m  the  wire.  The  extent  of  deflection  of 
the  needle  may  be  used  to  measure  the  strength  of  the  current  by  ascertaining 


Fig.  39.— D'Arsonval  galvanometer  as  modified  by  Rowland. 

the  amount  of  deflection  caused  by  a  standard  battery.  The  effect  of  the 
current  upon  the  needle  increases  with  the  number  of  turns  of  wire,  so  that 
delicate  galvanometers  constructed  upon  this  principle  are  spoken  of  as  high 
resistance  galvanometers,  the  great  length  of  wire  used  making,  of  course,  a 
high  resistance.  Instead  of  having  the  coil  through  which  the  current  passes 
kept  in  a  fixed  position  and  the  magnet  delicately  swung  or  poised,  the  reverse 
arrangement  may  be  used — that  is,  the  coil  may  be  swung  oetween  the  poles 
of  a  fixed  magnet.  Under  these  circumstances,  if  a  current  is  sent  through  the 
coil,  this  latter  will  move  with  reference  to  the  magnet.  A  galvanometer  con- 
structed on  this  principle  is  designated  as  a  d'Arsonval  galvanometer,  after 
the  physiologist  who  first  employed  this  arrangement.  In  the  d'Arsonval 
form  the  magnet  is  fixed  while  the  coil  of  wire  through  which  the  current 
passes  is  swung  by  a  very  delicate  thread  of  quartz,  silk  fiber,  or  phosphor- 
bronze.  The  principle  of  the  arrangement  is  shown  in  the  accompanying 
diagram  (Fig.  40)  and  one  form  of  a  complete  instrument  in  Fig.  39.  A  large 
horseshoe  magnet  (n,  s)  is  fixed  permanently  and  between  the  poles  is  swung 
a  coil  (c)  of  delicate  wire,  the  two  ends  of  the  wire  being  connected  with  binding 
posts  in  the  frame  of  the  instrument.  The  coil  is  held  in  place  below  by  a 
delicate  spiral.  In  Fig.  40  it  will  be  seen  that  the  delicate  thread  suspending 

7 


98 


THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 


the  coil  carries  just  above  the  coil  a  small  mirror,  m,  and  a  plate  of  thin  mica 
or  aluminum.  The  mirror  is  deflected  with  the  coil,  and  when  viewed  through 
the  telescope  pictured  in  Fig.  39  the  image  of  the  scale  above  the  telescope  is 
reflected  in  this  mirror.  As  the  coil  and  mirror  are  twisted  by  the  action 
of  the  current  passing  through  the  former  the  reflection  of  the  scale  in  the 
mirror  is  displaced.  By  means  of  a  cross  hair  in  the  telescope  the  angle  of 
deflection  may  be  read  upon  the  reflected  scale.  The  aluminum  vane  back  of 
the  mirror  makes  the  system  dead-beat,  so  that  when  a  deflection  is  obtained 


AJ4 


Fig.  40. — Diagram  of  struc- 
ture of  the  d' Arson val  galvanom- 
eter, c  is  the  coil  of  fine  wire 
through  which  the  current  is 
passed.  It  is  swung  by  a  fine 
thread  of  phosphor-bronze  so  as 
to  lie  between  and  close  to  the 
poles — (n)  north  pole,  and  (a) 
south  pole — of  the  magnet.  Just 
above  the  magnet  the  thread  car- 
ries a  mica  or  aluminum  vane  to 
which  is  attached  a  small  mirror. 
The  scale  of  the  instrument  is  re- 
flected in  this  mirror  and  is 
observed  through  the  telescope 
shown  in  Fig.  38. 


Fig.  41. — Schema  of  capillary  electrometei 
arranged  to  show  the  demarcation  current  t  in 
muscle  (Lombard) :  a.  The  glass  tube  containing 
mercury  and  drawn  to  a  fine  capillary  below;  c, 
the  receptacle  containing  mercury  by  raising 
•which  the  mercury  can  be  driven  into  the  capil- 
lary of  a;  /,  a  vessel  with  -1 
mercury  below, 


.  and  above  dilute  sulphuric 

into  which  the  capillary  of  a  dips;  E,  the  micro- 
cope  for  observing  the  mercury  thread  in  the 
capillary;  m,  the  muscle;  g  and  h,  the  wires 
touching  the  longitudinal  and  cut  surfaces  of  the 
muscle.  The  current  flows  as  indicated  by  the 
small  arrows;  d,  the  capillary  thread  of  mercury 
as  seen  under  the  microscope. 


the  system  comes  quickly  to  rest  with  few  or  no  oscillations.  If  the  coil  of  wire 
contains  sufficient  turns,  enough  to  give  a  total  resistance  of  two  to  three 
thousand  ohms,  and  the  poles  of  the  magnet  are  brought  very  close  to  the 
coil,  the  instrument  may  be  given  a  delicacy  sufficient  to  study  accurately  the 
muscle  and  nerve  currents.  In  such  an  instrument  the  effect  of  the  earth's 
magnetism  may  be  neglected  and  the  galvanometer  may  be  hung  upon  any 
support  without  reference  to  the  magnetic  meridian. 

The  movable  system  of  this  galvanometer  possesses  considerable  inertia, 
so  that  it  will  not  indicate  accurately  the  presence  or  extent  of  very  brief 
electrical  currents  such  as  have  to  be  studied  in  physiology  in  some  cases. 


ELECTRICAL    PHENOMENA. 


99 


For  purposes  of  this  kind  the  string-galvanometer  or  the  instrument  known 
as  the  capillary  electrometer  is  employed. 

The  String-galvanometer. — In  this  instrument  a  very  delicate  thread 
of  silvered  quartz  or  of  platinum  is  stretched  between  the  poles  of  a  strong 
magnet,  as  is  represented  in  the  diagrams  given  in  Figs.  42  and  43.  The 


Fig.  42. — One  form  of  the  string-galvanometer :   E,  The  electromagnet;  b,  the  projection 
microscope;  F,  a  screw  for  varying  the  tension  of  the  thread. — (Edelmann's  Catalogue.) 


Fig.  43. — Schema  to  show-  the  relation  of  the  thread  to  the  magnets  in  the  string- 
galvanometer  :  AA,  The  delicate  thread  of  silvered  quartz  or  of  platinum,  stretched  between 
the  polar  pieces  (PP)  of  an  electromagnet.  When  a  current  passes  through  AA,  the  thread 
shows  a  movement.  The  ends  of  the  magnets  are  pierced  by  holes,  seen  in  P\,  through 
which  the  movements  of  the  thread  may  be  watched  oy  means  of  a  microscope  or  be  pro- 
jected upon  a  photographic  plate. — (After  Einthoven.') 

metal  poles  of  the  magnet  are  pierced  by  holes,  so  that  the  thread  may  be 
illuminated  by  an  electric  light  (arc  light)  from  one  side,  and  on  the  other 
the  shadow  of  the  thread  may  be  thrown  upon  a  screen  after  being  magnified 
by  a  microscope  (see  Fig.  42).  With  this  arrangement  the  thread  shows  a 


100 


THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 


lateral  movement  whenever  a  current  is  passed  through  it.  The  instrument 
may  be  made  of  great  delicacy  so  as  to  detect  very  minute  currents,  and, 
moreover,  it  has  the  very  great  advantage  of  responding  accurately  to  rapid 
changes  in  potential.  If  the  shadow  of  the  thread  is  allowed  to  fall  upon 
sensitized  paper  properly  adjusted  upon  a  rotating  surface,  its  movements  may 
be  photographed  and  a  permanent  record  be  thus  obtained  (see  Fig.  22  for 
an  example  of  such  a  photographic  record  showing  the  electrical  changes  in 
a  contracting  muscle). 

The  Capillary  Electrometer. — The  principle  of  the  construction  of 
the  capillary  electrometer  is  illustrated  in  Fig.  41.  A  glass  tube,  a,  is  drawn 
out  at  one  end  into  a  very  fine  capillary,  the  end  of  which  dips  into  some 
diluted  sulphuric  acid  contained  in  the  vessel  (/).  At  the  bottom  of  this 
vessel  is  a  layer  of  mercury  connecting  with  a  wire,  g,  fused  into  the  glass 
vessel.  The  tube  a  is  partially  filled  with  redistilled  mercury,  which  pene- 
trates for  a  short  distance  into  the  capillary.  By  means  of  pressure  applied 
from  above  c,  the  mercury  can  be  forced  through  the  capillary.  Then  by 
diminishing  the  pressure  the  mercury  can  be  brought  back  into  the  capillary 
a  certain  distance,  drawing  after  it  some  of  the  dilute 
sulphuric  acid.  The  mercury  in  tube  a  is  connected 
with  the  other  pole  of  the  battery  by  a  wire  fused  into 
its  wall  and  dipping  into  the  mercury.  By  regulating 
the  pressure  on  the  mercury  the  point  of  contact  be- 
tween the  thread  of  mercury  and  the  sulphuric  acid 
in  the  capillary,  d,  can  be  brought  to  any  desired 
position.  An  equilibrium  is  then  established  which 
will  remain  constant  as  long  as  the  conditions  are  not 
changed.  If  now  the  circuit  from  a  battery  or  other 
source  of  electricity — for  example,  the  excised  nerve 
or  muscle — is  closed,  the  current  entering  by  wire  g, 
if  this  represents  the  anode,  traverses  the  sulphuric 
acid  and  mercury  in  the  capillary  and  returns  by  the 
wire  h.  At  the  moment  of  the  establishment  of  the 
current  the  equilibrium  of  forces  that  holds  the  mer- 
cury at  a  certain  point  in  the  capillary  is  disturbed, 
the  end  of  the  mercury  thread  moves  upward  with 
the  current  for  a  certain  distance,  depending  on  the 
strength  of  the  current  and  the  delicacy  of  the  capillary. 
If  the  current  be  passed  in  the  opposite  direction  the 
mercury  will  move  downward  a  certain  distance.  The 
meniscus  of  contact  moves  up  or  down  with  the  direc- 
tion of  the  current,  owing,  it  is  supposed,  to  a  change 
in  the  surface  tension  at  this  point.  The  capillary  tube 
as  used  for  physiological  purposes  is  too  small  for  the 
movements  of  the  mercury  to  be  detected  with  the  eye. 
It  is  necessary  to  magnify  it  either  with  a  microscope 

with  physioi  or  a  Pr°Jection  lantern.     Ordinarily  the  electrometer 

line  (NaCl,  0.7  per  is  so  made  that  it  can  be  placed  upon  the  stage  of  the 
cent.)  (this  is  placed  on  microscope  and  the  capillary  be  brought  into  focus 
at  the  meniscus,  as  shown  in  d,  Fig.  41 1  By  means  of 
proper  apparatus  the  movement  can  be  photographed 
and  thus  a  permanent  record  be  obtained  of  the  direc- 
tion and  extent  of  movement  of  the  mercury. 
Non-polarizable  Electrodes. — In  connecting  a  muscle  or  nerve  to  an  elec- 
trometer or  galvanometer  it  is  necessary  that  the  leading  off  electrodes — 
that  is,  the  point  of  contact  between  the  wires  and  the  muscle  or  nerve — 
shall  be  iso-electric  and  non-polarizable.  By  iso-electric  is  meant  that  the 
two  electrodes  have  the  same  electrical  potential,  and  it  is  obvious  that  the 
leading  off  electrodes  must  fulfil  this  condition  approximately  at  least,  since 
otherwise  the  current  obtained  from  the  muscle  or  nerve  could  not  be  attrib- 
uted to  differences  in  potential  in  the  tissue  itself;  it  would  be  shown  by  any 
other  moist  conductor  connecting  the  two  electrodes.  Two  clean  platinum 
electrodes  would  fulfil  this  condition.  A  more  serious  difficulty  is  found  in 


Fig.  44— To  show 
the  structure  of  a  non- 
polarizable  electrode : 
1,  The  pad  of  kaolin  or 
filter  paper  moistened 
with  physiological  sa- 
line (NaCl,  0 
cent.)  (this  is  place  on 
the  tissue) ;  2,  the  sat- 
urated solution  of  zinc 
sulphate;  (3)  the.  bar 
of  amalgamated  zinc. 


ELECTRICAL    PHENOMENA. 


101 


the  polarization  of  metallic  electrodes.  Whenever  a  metal  conductor  and  a 
liquid  conductor  come  into  contact  there  is  apt  to  be  polarization.  What 
takes  place  may  be  represented  by  the  following  diagram,  in  which  a  current 
fe  supposed  to  be  passing 


Na       Na 
CI         CI 


between  the  poles  A  and  C  through  a  solution  of  sodium  chlorid.  During 
the  passage  of  the  current  the  cations,  Na,  with  their  positive  charges 
move  toward  the  cathode;  at  the  cathode  the  free  sodium  ion  acts  upon 
the  water,  HHO,  forming  NaOH  and  liberating  hydrogen,  which  accumu- 
lates upon  the  cathode  in  the  form  of  gas.  The  anions,  CI,  with  their  negative 
charges  move  toward  the  anode;  there  the  chlorin  acts  upon  the  water,  form- 
ing HC1  and  liberating  oxygen.  In  consequence  of  this  accumulation  of 
gases  upon  the  poles  a  gas  battery  is  formed,  in  which  the  direction  of  current 
is  against  that  of  the  main  current,  that  is,  from  C  to  A.  It  is  obvious  that 
in  quantitative  studies  of  the  electrical  currents  of  animal  tissues  polari- 
zation will  destroy  the  accuracy  of  the  results;  the  demarcation  current 
will  show  a  diminution  due  not  to  changes  in  the  nerve,  but  to  physico- 
chemical  changes  at  the  leading-off  electrodes.  To  prevent  polarization 
du  Bois-Reymond  devised  the  non-polarizable  electrodes  consisting  of  zinc 
terminals  immersed  in  zinc  sulphate.  Theoretically  any  metal  in  a  solution 
of  one  of  its  salts  may  be  used,  but  experience  shows  that  the  zinc-zinc  sulphate 
electrode  is  most  nearly  perfect.  Each  electrode  where  it  comes  into  contact 
with  the  tissue  is  made  of  one  of  these  combinations.  Various  devices  have 
been  used.  For  instance,  the  electrode  may  be  constructed  as  shown  in  the 
diagram  (Fig.  44).  A  short  glass  tube  of  a  bore  of  about  4  mms.  is  well 
cleaned — one  end,  which  is  to  come  into  contact  with  the  nerve — is  filled,  as 
shown,  by  a  plug  of  kaolin  made  into  a  stiff  putty  with  physiological  saline 
solution  of  NaCl  (0.7  per  cent.).  The  kaolin  should  have  a  neutral  reaction 
and  unless  good  kaolin  is  obtainable  it  is  better  to  use  a  plug  made  of  clean 
filter  paper  macerated  in  physiological  saline  and  packed  tightly  into  the  end 
of  the  tube.  Above  this  plug  the  tube  is  filled  in  for  a  part  of  its  length  with 
a  saturated  solution  of  zinc  sulphate  into  which  is  immersed  a  bar  of  amal- 
gamated zinc  with  a  copper  wire  soldered  to  its  end.  With  a  pair  of  such 
electrodes  the  conduction  of  the  current  through  the  nerve  or  muscle  to  the 
metallic  part  of  the  circuit  may  be  represented  as  follows: 


Zn 


so4    so4    ci      ci      a      so4    so4 


Zn 


The  liquid  part  of  the  circuit  comes  into  contact  with  the  metallic  part 
at  the  junction  of  Zn  and  ZnSO4.  At  the  cathode  it  may  be  supposed  that 
the  Zn  cation  instead  of  acting  upon  the  water  and  liberating  hydrogen, 
deposits  itself  upon  the  zinc  electrode;  at  the  anode  the  sulphion  (SOJ 
attacks  the  zinc  instead  of  the  water,  forming  ZnSO4.  In  this  way  polarization 
is  prevented,  and  by  the  construction  of  the  electrode  the  living  tissue  is 
brought  into  contact  only  with  the  plug  of  kaolin  moistened  with  physio- 
logical saline.  ^  Such  electrodes  are  indispensable  in  studying  the  electrical  phe- 
nomena of  living  tissues,  and  also  in  all  investigations  bearing  upon  the  polar 
effects  during  the  passage  of  an  electrical  current  from  a  battery.  Ordinarily, 
however,  when  it  is  only  desired  to  stimulate  a  nerve  or  muscle,  metal  (plat- 
inum) electrodes  are  employed. 


102  THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 

The  Action  Current  or  Negative  Variation. — Du  Bois-Rey- 
mond  proved  that  when  the  excised  muscle  or  nerve  is  stimulated 
its  demarcation  current  suffers  a  diminution  or  negative  variation. 
If,  for  instance,  the  excised  nerve  gives  a  demarcation  current  suf- 
ficient to  cause  a  deflection  in  the  galvanometer  of  50  mms.,  then 
if  the  nerve  is  stimulated  by  a  series  of  induction  shocks  the  galva- 
nometer will  show  a  lessened  deflection,  say,  one  of  40  mms.  The 
negative  variation  in  this  case  is  equal  to  10  mms.,  on  the  scale  of 
the  galvanometer  used.  It  has  been  shown  that  this  negative  varia- 
tion is  due  to  a  current  in  the  opposite  direction  whose  strength,  in 
the  example  given,  relative  to  that  of  the  demarcation  current  is 
as  10  to  50.  Frequently  the  phenomenon  of  the  negative  varia- 
tion is  known  also  as  the  action  current.  The  explanation  given 
for  this  action  current  is  that  the  nerve  or  muscle  when  excited 
takes  on  an  electrical  condition  which  is  negative  as  regards  any 
unexcited  or  less  excited  portion  of  the  nerve.  The  effect  upon  the 
demarcation  current  is  illustrated  in  the  accompanying  diagram. 

The  demarcation  current  in  a  nerve  is  led  off  to  a  galvanometer 
by  electrodes  placed  at  b  and  c.  When  the  nerve  is  stimulated  at 
a  the  excitation  set  up  passes  along  the  nerve,  and  wherever  it  may 
be  that  portion  of  the  nerve  is  thrown  into  an  electronegative  condi- 
tion. When  this  condition  reaches  a  point  at  which  it  can  influence 
the  galvanometer — that  is,  when  it  reaches  6,  it  will  dimmish  the 
difference  in  potential  that  exists  between  b  and  c,  and  therefore 

reduce  the  current 

_4_  flowing  from  b  to  c. 

Bernstein*  has 
shown  that  this  neg- 
ative condition 
moves  in  the  form  of 
a  wave.  That  is,  at 
any  point  the  nega- 

Fig.  45.— Schema  to  indicate  the  method  of  detecting  tivity    grOWS     to     a 

the  action  current  in  a  stimulated  excised  nerve:    6  and  c,  maximum  and  then 

the  leading  off  electrodes,  one  on  the  longitudinal,  one   on  .    . 

the  cut  surface;    the  demarcation  current  passes  through  diminishes.       More- 

the  galvanometer,  g,  in  the  direction  of  the  arrows ;  a,  stimu-  .                  , 

lating  electrodes  from  induction  coil ;   the  stimulus  causes  a  OVCr,  it  travels  at  B, 

negative  condition, — which  passes  along  the  nerve;    when  •,    fi    .,           T^1  ~  „:  *  „, 

this   reaches  b  it  causes  a  partial   reversal  of  the   demarca-  aennite      VClOClty 

tion  current,  giving  the  negative  variation   or  action  cur-  which       js       easily 

measured.  Accord- 
ing to  his  experiments,  the  velocity  of  this  wave  in  the  frog's 
motor  nerve  is  from  25  to  28  meters  per  second,  and  the  length 
of  the  wave  is  about  18  mms.  Hermann,  on  the  contrary,  be- 
lieves that,  in  the  excised  nerve  at  least,  the  length  of  the  wave 
may  be  greater,  reaching  perhaps  140  mms. 

*  Bernstein,  "  Untersuchungen  iiber  den  Erregungsvorgang  im  Nerven 
und  Muskelsysteme,"  Heidelberg  1871. 


ELECTRICAL    PHENOMENA.  103 

These  figures  will  vary  naturally  for  the  nerves  of  different  ani- 
mals or  for  different  nerves  in  the  same  animal,  for  it  must  always 
be  remembered  that  nerve  fibers,  whose  functions  in  general  are  so 
similar,  differ  much  in  obvious  microscopical  structure  and  probably 
more  widely  in  their  chemical  composition.  Using  an  analogy  that 
is  familiar,  we  may  say  that  when  a  stimulus  acts  upon  a  living 
nerve  a  wave  of  elect ronegativity  spreads  from  the  stimulated 
spot  and  travels  in  wave  form  wit!  a  definite  velocity,  just  as  water 
waves  radiate  from  the  spot  at  which  a  stone  is  thrown  into  a  quiet 
pool.  A  similar  phenomenon  occurs  in  muscle  fibers  when  stimu- 
lated, but  the  negative  condition  travels  over  the  muscle  fiber  at  a 
slower  speed,  3  to  4  meters  per  second  in  frog's  muscle,  and  with  a 
wave  length,  according  to  Bernstein,  of  only  10  mms.  This  wave 
of  negativity  in  the  muscle  begins  during  the  latent  period  and, 
therefore,  precedes  the  actual  shortening  at  any  point. 

This  phenomenon  of  a  negative  electrical  condition  traveling 
over  the  nerve  or  muscle  and  giving  us  an  action  current  when  led 
off  through  a  galvanometer  is  of  the  greatest  physiological  impor- 
tance, particularly  in  the  study  of  nerves.  It  has  been  shown 
that  in  the  nerve  this  wave  of  negativity  marks  the  progress  of  the 
wave  of  excitation,  and,  since  we  can  study  its  progress  by  means 
of  the  galvanometer  or  capillary  electrometer,  we  can  thus  study  the 
excitability  and  conductivity  in  nerves  when  removed  from  con- 
nection with  their  end-organs.  That  the  negative  wave,  or  the 
action  current  that  it  gives  rise  to,  is  an  invariable  sign  of  the 
passage  of  an  excitation  or  nerve  impulse  is  shown  by  the  facts 
that  it  is  absent  in  the  dead  nerve,  and  that  hi  the  living  nerve  it  is 
produced  by  mechanical,*  chemical,  f  and  reflex  t  stimulations,  as 
well  as  by  the  more  usual  method  of  electrical  stimulation. 

Monophasic  and  Diphasic  Action  Currents. — According  to 
the  conception  of  the  action  current  given  above,  it  is  evident  that 
it  should  be  obtained  upon  stimulation  when  a  living  normal  nerve 
is  connected  at  any  two  points  of  its  course  with  a  galvanometer  or 
capillary  electrometer.  The  detection  of  the  current  under  such 
conditions  offers  more  difficulties,  because  it  is  diaphasic,  as  will 
be  seen  from  the  accompanying  diagram  (Fig.  46).  The  figure 
represents  a  normal  nerve  led  off  to  the  galvanometer  from  two 
points,  b  and  c,  of  its  longitudinal  surface.  As  these  points  in  the 
uninjured  nerve  have  the  same  potential,  no  current  is  shown  by 
the  galvanometer.  If  the  nerve  is  stimulated  at  a  by  a  single 
stimulus,  a  negative  condition  or  charge  passes  along  the  nerve. 
When  it  reaches  the  point  6,  there  will  be  a  momentary  current 

*  Steiuach,  "Pfliiger's  Archiv,"  55,  487,  1894. 
t  Griitzner,  "Pfliiger's  Archiv,'"  25,  255,  1881. 
j  Boruttau,  "Pfliiger's  Archiv,"  84,  and  90,  1901-1902. 


104  THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 

through  the  galvanometer  from  c  to  6;  as  the  charge  passes  on 
to  c,  this  point  in  turn  will  become  negative  to  6,  and  there  will 
be  a  momentary  current  through  the  galvanometer  in  the  other 
direction.  The  diphasic  current  that  occurs  under  these  con- 
ditions cannot  be  detected  by  the  ordinary  galvanometer,  even 
when  a  series  of  stimuli  is  sent  into  the  nerve  at  a,  since  the 
movable  system  in  this  instrument  has  too  much  inertia  to 
respond  to  such  quick  changes  in  opposite  directions.  With 
the  more  mobile  string-galvanometer  or  capillary  electrometer 
the  diphasic  currents  have  been  demonstrated  successfully.  In 
laboratory  investigations  one  of  the  leading  off  electrodes,  c, 
is  usually  placed  on  the  cut  end  of  the  nerve.  Under  this  con- 
dition the  action  current  becomes  monophasic  and  shows  itself 
as  a  negative  variation  of  the  demarcation  current.  This 
difference  is  due  to  the  fact  that  the  negative  condition  accompany- 
ing or  constituting  the  wave  of  excitation  undergoes  a  decrement 
as  it  enters  a  region  in  which  a  negative  condition  already  pre- 
vails. Therefore,  when  the  leading-off  electrodes  are  placed  so 
that  one  is  on  the  longitudinal  and  one  on  the  cut  surface,  the 
change  of  potential  accompanying  the  excitation  will  affect  only 
the  first  electrode  (6)  and  give  a  monophasic  variation,  which  can 
now  be  shown  by  the  usual  galvanometer,  provided  a  series  of 
stimuli  is  thrown  in  at  a. 


Fig.  46. — Schema  to  show  the  arrangement  for  obtaining  a  diphasic  action  current. 
The  arrangement  differs  from  that  in  Fig.  42  only  in  that  both  leading  off  electrodes,  6  and 
c,  are  placed  on  the  longitudinal  surface.  No  demarcation  current  is  indicated.  When 
the  nerve  is  stimulated  at  a  the  negative  charge  reaches  6  first,  causing  a  current  through 
the  galvanometer  from  c  to  b.  Subsequently  it  reaches  c  and  causes  a  second  current 
in  the  opposite  direction  from  6  to  c. 

The  Positive  Variation. — It  happens  not  infrequently  that  when  one 
electrode  is  placed  upon  the  cut  end,  the  nerve  upon  stimulation  with  a  series 
of  induction  shocks  gives  a  positive  instead  of  a  negative  variation  of  the 
demarcation  current.  This  result  is  usually  explained  as  being  due  to  a  pre- 
dominance of  the  anelectrotonic  currents  (see  below).  When  this  phenomenon 
occurs  it  can  usually  be  avoided  by  making  a  fresh  section  at  the  end  of  the 
nerve. 

Detection  of  the  Action  Currents  by  the  Rheoscopic  Frog 
Preparation  or  by  the  Telephone. — The  motor  nerve  of  a  nerve- 
muscle  preparation  from  a  frog  is  so  extremely  irritable  to  electrical 
currents  that  it  may  be  used  instead  of  a  galvanometer  to  detect 


ELECTRICAL    PHENOMENA 


105 


the  action  currents  in  a  stimulated  muscle.  A  nerve-muscle  prep- 
aration used  for  this  purpose  is  known  as  a  rheoscopic  preparation. 
The  way  in  which  it  is  used  is  indicated  in  the  accompanying 
diagram,  b  represents  the  rheoscopic  preparation,  its  nerve  being 
laid  upon  the  muscle  whose  currents  are  being  investigated,  a,  so  as 
to  touch  the  cut  end  (x)  and  the  longitudinal  surface  (</).  When  a  is 
stimulated,  either  directly  or  through  its  nerve,  as  represented  in  the 
diagram,  the  negative  changes  that  pass  along  the  muscle  fibers  of 
a  with  each  stimulus  cause  action  currents  that  will  be  led  off 
through  the  nerve  of  b  from  x  to  g.  If  the  nerve  is  in  a  sensitive  con- 
dition it  will  be  stimulated  by  the  action  currents  and  thus  a  series  of 
excitations  will  be  sent  into  b  corresponding  exactly  in  rate  with 
the  artificial  stimuli  given  to  the  nerve  of  a.  The  rheoscopic 
preparation  may  be  used  very  beautifully  to  demonstrate  the 
action  current  in  the  contracting  heart  muscle.  If  the  nerve  of 
b  is  laid  upon  the  exposed  beating  heart  of  an  animal,  the  muscle 
of  b  will  give  a  single  twitch  for  each  beat  of  the  ventricle.  An- 
other interesting  method  of  detecting  the  action  currents,  particu- 
larly in  nerves,  is  by  means  of  the  telephone.  Wedenski  has  made 
especial  use  of  this  method,  the  telephone  being  connected  with 


Fig.  47. — Schema  to  show  the  arrangement  of  a  rheoscopic  muscle-nerve  preparation: 
6,  The  rheoscopic  muscle-nerve  preparation,  the  nerve  being  arranged  to  touch  the  cut  sur- 
face and  the  longitudinal  surface  of  the  muscle,  a,  whose  action  currents  are  to  be  detected. 
When  the  nerve  of  a  is  stimulated  each  contraction  of  this  muscle  is  followed  by  a  contrac- 
tion of  6,  since  each  contraction  of  a  is  accompanied  by  an  action  current  which  passes 
through  the  nerve  of  6  and  stimulates  it. 

the  nerve  in  place  of  the  galvanometer.  The  method  has  obvious 
advantages  in  the  fact  that  it  may  be  used  with  a  nerve  to  which 
the  muscle  is  also  attached,  so  that  the  excitation  processes  in 
the  nerve  and  their  effect  upon  the  muscle  may  be  studied  simul- 
taneously. 

Relation  of  the  Action  Current  to  the  Contraction  Wave 
in  Muscle  and  to  the  Excitation  Wave  (Nerve  Impulse)  in  Nerve. — 
The  action  current  or,  to  be  more  accurate,  the  moving  negative 
potential,  which  gives  rise  to  an  action  current  when  two  points 
of  the  mus.de  are  led  off  to  a  galvanometer,  has  been  shown 


106 


THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 


by  Bernstein  to  precede  the  wave  of  contraction  in  muscle;  that 
is,  in  a  stimulated  muscle  fiber  the  electrical  change  at  any  point 
precedes  the  mechanical  process  of  shortening.  This  relation- 
ship is  shown  in  the  accompanying  illustration  (Fig.  48),  in  which 
the  mechanical  contraction  (movement  of  the  lever)  is  photo- 
graphed simultaneously  with  the  movement  of  the  string  of  the 
string-galvanometer  which  indicates  the  electrical  change.  As 
the  figure  shows  the  electrical  change  is  diphasic,  owing  to  the  op- 
posite effects  on  the  galvanometer  of  the  change  of  potential  at 


AAA    I 


Fig.  48. — Simultaneous  record  of  the  mechanical  and  electrical  change  in  a  contracting 
muscle:  1,  Mechanical  curve  of  contraction,  photograph  of  the  lever;  2,  movement  of  the 
string  of  the  string-galvanometer  (owing  to  its  faintness  it  was  necessary  to  retouch  this 
curve) ;  movement  upward  indicates  an  increase  of  negative  potential  at  the  upper  end  of  the 
muscle;  3,  time  record  in  hundredths  of  a  second;  4,  the  stimulating  lever;  the  break  in  the 
line  indicates  the  moment  of  stimulation;  on  the  curve  of  contraction  (1)  this  moment  is 
indicated  by  x;  on  the  curve  showing  the  movement  of  the  string  (2)  the  same  instant  is 
marked  by  the  small  nick  in  the  curve  preceding  the  large  wave  caused  by  the  electrical 
change.  The  curve  was  obtained  from  the  gastrocnemius  muscle  of  a  frog,  stimulated 
through  its  nerve  by  a  single  induction  shock,  contraction  isotonic.  The  leading-off  electrodes 
were  placed  at  the  ends  of  the  muscle;  galvanometer  string  under  tension.  The  electric  curve 
is  diphasic,  and  both  phases  are  completed  within  the  latent  period  of  contraction  (Snyder). 


the  two  points  lead  off  to  the  galvanometer,  and  is  completed 
before  the  muscle  begins  to  shorten.  We  may  suppose  that 
the  electrical  change  is  an  indication  of  the  excitation,  or  pos- 
sibly constitutes  the  excitation  that  sets  up  the  chemical  change 
of  contraction,  or  else  that  the  change  in  electrical  potential 
is  caused  by  the  chemical  change  of  contraction  and  precedes 
the  mechanical  result  of  shortening,  since  the  latter  process 
will  have  a  certain  latent  period.  It  has  been  shown,  indeed, 
by  Demoor  that  a  completely  fatigued  muscle  may  still  con- 
duct an  excitation  (muscle  impulse),  although  unable  to  con- 
tract, and  the  same  fact  has  been  demonstrated  by  Engelmann 
for  the  heart  muscle.  In  the  nerve  the  action  current,  or  the 
negative  change  causing  it,  has  been  considered  as  simultaneous 


ELECTRICAL    PHENOMENA. 


107 


D 


with  or  possibly  identical  with  the  nerve  impulse.  The  velocity 
of  the  two  is  identical;  the  action  current  is  given  whenever  the 
nerve  is  stimulated,  and,  so  far  as  experiments  have  gone,  the 
nerve  cannot  enter  into  activity  without  showing  an  action 
current, — that  is,  without  showing  a  moving  electrical  change. 
Whether  this  electrical  change  constitutes  the  nerve  impulse  or 
is  simply  an  accompanying  phenomenon  will  be  discussed  briefly 
in  the  paragraph  upon  the  nature  of  the  nerve  impulse  in  the 
following  chapter. 

The  Electrotonic  Currents. — In  speaking  of  the  effect  of 
passing  a  galvanic  current  through  a  nerve  attention  was  called 
to  the  fact  that  the 
condition  of  the 
nerve  is  altered  at 
each  pole.  At  the 
anode  there  is  a  con- 
dition of  decreased 
irritability  and  con- 
ductivity known  as 
anelectrotonus  ;  a  t 
the  cathode,  in  the 
beginning,  at  least, 
a  condition  of  in- 
creased irritability 
known  as  catelec- 
trotonus.  In  addi- 
tion to  these  changes  in  the  physiological  properties  of  the  nerve 
there  is  a  change  also  in  its  electrical  condition  at  each  pole,  of 
such  a  character  that  if  the  nerve  is  led  off  from  two  points  on 
the  anode  side  a  current  will  be  indicated.  The  current  can  be 
obtained  at  a  considerable  distance  from  the  anode,  and  is  known 
as  the  anelectrotonic  current,  while  the  electrical  condition  in  the 
nerve  that  makes  it  possible  is  designated  as  anelefctrotonus.  A 
similar  current  can  be  led  off  from  the  nerve  on  the  cathode  side 
for  a  considerable  distance  beyond  the  cathode;  this  is  known  as 
the  catelectrotonic  current,  and  the  electrical  condition  leading 
to  its  production  as  catelectrotonus.  Within  the  nerve  these 
electrotonic  currents  have  the  same  direction  as  the  battery  or 
polarizing  current,  as  is  shown  in  the  diagram  (Fig.  49),  The 
terms  anelectrotonus  and  catelectrotonus  are  used,  therefore, 
in  physiology  to  designate  both  the  physiological  and  the  elec-* 
trical  changes  around  the  poles  when  a  battery  current  is  led 
into  a  nerve.  Whether  the  physiological  and  the  electrical  changes 
have  a  causal  connection  or  are  two  independent  phenomena  is 
at  present  undecided. 


Fig.  49. — Schema  to  show  the  direction  of  the  elec- 
trotonic currents  in  an  excised  nerve:  P,  The  battery  for 
the  polarizing  current  sent  into  the  nerve  at  +»  the  an- 
ode, and  emerging  at  — ,  the  cathode;  a*,  galvanometer 
arranged  with  leading  off  electrodes  to  detect  the  anelec- 
trotonic current,  the  direction  of  which  is  indicated  by 
the  arrows  (in  the  nerve  it  is  the  same  as  that  of  the  po- 
larizing current);  g,  galvanometer  similarly  arranged  to  de- 
tect the  catelectrotonic  current.  The  anelectrotonic  and 
catelectrotonic  currents  continue  as  long  as  the  polarizing 
current  is  maintained. 


108 


THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 


Hermann*  has  suggested  a  relatively  simple  explanation  of  these  currents. 
He  constructed  a  model  consisting  of  a  conductor  surrounded  by  a  less  con- 
ductive liquid  sheath,  and  showed  that  such  a  model  is  capable  of  giving  the 
electrotonic  currents.  This  model  may  be  made  as  represented  in  the  ac- 
companying diagram,  of  a  glass  tube  A—B,  through  the  middle  of  which  is 
stretched  a  platinum  wire,  P,  the  rest  of  the  tube  being  filled  with  a  saturated 
solution  of  zinc  sulphate.  The  glass  tube  is  provided  with  vertical  branches  by 
means  of  which  a  polarizing  current,  p,  can  be  sent  into  the  solution  of  zinc 
sulphate  and  the  electrotonic  currents  be  led  off  to  galvanometers,  g',  g,  on 
each  side.  Under  these  conditions  a  current  similar  to  the  anelectrotonic 
current  can  be  detected  on  the  side  of  the  anode  (g'}  and  one  equivalent  to 
the  catelectrotonic  current  on  the  side  of  the  cathode  (g).  The  explanation 
given  to  these  currents  is  that  as  the  threads  of  current  pass  into  the  platinum 
core  there  is  a  polarization  at  the  surface  between  the  core  and  the  zinc  sul- 
phate solution  which  extends  to  a  considerable  distance  on  each  side  of  the 
electrodes  and  causes  diffusion  currents  from  sheath  to  core.  It  is  these 
threads  of  current  that  may  be  led  off  as  electrotonic  currents.  Hermann 
suggested  that  in  the  nerve  we  have  a  structure  essentially  similar  to  that 


ff 


Fig.  50. — To  show  the  action  of  the  core-model:  p,  The  polarizing  current;  g'  and 
g,  the  galvanometers  with  leading  off  electrodes  to  detect  the  anelectrotonic  and  cateleo 
trotonic  currents,  respectively. 

of  the  core  model.  He  thought  that  the  axis  cylinder  might  be  considered 
as  representing  the  core  and  the  myelin  the  less  conductive  sheath  corre- 
sponding to  the  zinc  sulphate  solution.  Others  (Boruttau)  have  suggested 
that  the  neurofibrils  in  the  axis  cylinder  may  represent  the  core  or  cores  and 
the  surrounding  neuroplasm  the  sheath,  thus  providing  for  the  possibility  of 
electrotonic  currents  in  non-medullated  fibers.  As  a  matter  of  fact,  the  non- 
medullated  fibers  in  mammals  give  very  slight  electrotonic  currents  compared 
with  the  medullated  fibers.f 

According  to  the  "core-model"  explanation,  the  electrotonic  currents 
represent  a  purely  physical  phenomenon,  which  is  dependent,  however,  upon 
a  certain  structure  of  the  nerve.  That  is,  a  completely  dead  nerve  will  not 
show  these  curients,  although  an  anesthetized  nerve,  in  the  mammal  (Waller) 
at  least,  continues  to  show  them,  and,  according  to  Sosnowsky,  excised  rab- 
bits' nerves  kept  in  a  moist  atmosphere  may  show  them  for  several  days. 

*  Hermann,  "Handbuch  der  Physiologic,"  vol.  ii,  p.  174. 
t  Alcock,  "Proceedings  Royal  Society,"  1904,  73,  p.  166. 


CHAPTER  V. 

THE  NATURE  OF  THE  NERVE  IMPULSE  AND  THE 

NUTRITIVE  RELATIONS  OF  NERVE  FIBER 

AND  NERVE  CELL. 

The  question  of  the  nature  of  the  nerve  impulse  has  always 
aroused  the  deepest  interest  among  physiologists.  It  has  consti- 
tuted, indeed,  a  central  question  around  which  have  revolved  vari- 
ous hypotheses  concerning  the  nature  of  living  matter.  The  impor- 
tance of  the  nerves  as  conductors  of  motion  and  sensation  was 
apparent  to  the  old  physiologists,  and  the  nature  of  the  conduction 
or  the  thing  conducted  was  the  subject  of  many  hypotheses  and 
many  different  names.  For  many  years  the  prevalent  view  was 
that  the  nerves  are  essentially  tubes  through  which  flows  an  ex- 
ceedingly fine  matter,  of  the  nature  of  air  or  gas,  known  as  the 
animal  spirits.  Others  conceived  this  fluid  to  be  of  a  grosser  struc- 
ture like  water  and  described  it  as  the  nerve  juice.  With  Galvani's 
discovery  of  electricity  the  nerve  principle,  as  it  was  called,  became 
identified  with  electricity,  and,  indeed,  this  view,  as  will  be  ex- 
plained, occurs  in  modified  form  to-day.  Du  Bois-Reymond, 
after  discovering  the  demarcation  current  and  action  current  in 
muscle  and  nerve,  formulated  an  hypothesis  according  to  which  the 
nerve  fibers  contain  a  series  of  electromotive  particles,  and  by 
this  hypothesis  and  the  facts  upon  which  it  was  based  he  thought 
that  he  had  established  that  "hundred-year-old  dream"  of  phys- 
icists and  physiologists  of  the  identity  of  the  nerve  principle 
and  electricity.  His  theory  to-day  has  fallen  into  disrepute,  but 
the  facts  upon  which  it  was  based  remain,  as  before,  of  the  deepest 
importance.  In  the  middle  of  the  nineteenth  century  those  who 
were  not  convinced  of  the  identity  of  the  nerve  principle  with 
electricity  believed,  nevertheless,  that  the  process  of  conduction 
in  the  nerve  is  a  phenomenon  of  an  order  comparable  to  the  trans- 
mission of  light  or  electricity,  with  a  velocity  so  great  as  to  defy 
measurement.  But  in  this  same  period  a  simple  but  complete 
experiment  by  Helmholtz  demonstrated  that  its  velocity  is,  as 
compared  with  light  or  with  electrical  conduction  through  the  air 
or  through  metals,  exceedingly  slow,  27  to  125  meters  per  second. 
Modern  views  have  taken  divergent  directions;  the  movement 
or  excitation  that  is  conducted  along  the  fiber  has  been  named 

109 


110 


THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE. 


the  nerve  principle,  the  nerve  energy,  the  nerve  force,  the  nerve 
impulse.  As  the  latter  term  is  less  specific  regarding  the  nature 
of  the  movement,  and  emphasizes  the  fact  of  the  conduction  of  an 
isolated  disturbance  or  pulse,  it  seems  preferable  to  employ  it 
until  a  more  satisfactory  solution  of  its  nature  has  been  reached. 
The  Velocity  of  the  Nerve  Impulse. — The  determination  of 
the  velocity  of  the  nerve  impulse  was  first  made  by  Helmholtz* 
upon  the  motor  nerves  of  frogs.  His  experiment  consisted  in 
stimulating  the  sciatic  nerve,  first,  near  its  ending  in  the  muscle 


Fig.  51. — Record  to  show  the  method  of  estimating  the  velocity  of  the  nerve  impulse 
in  a  motor  nerve.  The  experiment  was  made  upon  a  nerve-muscle  preparation  from  the 
frog,  the  contractions  bring  recorded  upon  the  rapidly  moving  plate  of  a  pendulum  myo- 
graph.  Two  contractions  were  obtained,  the  first  (a)  when  the  nerve  was  stimulated 
near  the  muscle,  the  second  (6)  when  the  nerve  was  stimulated  as  far  as  possible  from  the 
muscle.  The  latent  period  of  the  second  contraction  was  longer,  as  shown  by  the  distance 
between  the  curves  measured  on  the  line  x.  The  value  of  this  distance  in  time  is  obtained 
by  reference  to  the  record  of  a  tuning  fork  vibrating  100  times  per  second,  which  is  given 
on  the  lower  line.  In  the  experiment  the  length  of  a  tuning  fork  wave  (0.01  sec.)  was  21 
mms.,  the  distance  between  the  two  muscular  contractions  was  3.35  mms.,  and  the  dis- 
tance between  the  points  stimulated  upon  the  nerve  was  49  mms.  Hence  the  velocity  of  the 
nerve  impulse  in  this  experiment  was  49  divided  by  (^jVff  X  j^)  or  30716  mms.  (30.716  m.) 
per  second. 

and,  second,  near  its  origin  from  the  cord,  and  measuring  the  time 
that  elapsed  in  each  case  between  the  moment  of  stimulation  and 
the  moment  of  the  muscular  response.  It  was  found  that  when 
the  nerve  was  stimulated  at  its  far  end  this  time  interval  was 
longer,  and  since  all  other  conditions  remained  the  same  this  dif- 
ference in  time  could  only  be  due  to  the  interval  required  for  the 
nerve  impulse  to  travel  the  longer  stretch  of  nerve.  In  the  accom- 

*  Helmholtz,  "  Miiller's  Archiv  f.  Anat.  u.  Physiol.,"  1852,  p.  199. 


NATURE    OF    THE    NERVE    IMPULSE.  Ill 

panying  figure  the  record  of  a  laboratory  experiment  of  this  kind 
is  reproduced.  Knowing  the  difference  in  time  and  also  the  length 
of  nerve  between  the  points  stimulated,  the  data  are  at  hand  to 
calculate  the  velocity  of  the  impulse.  The  velocity  varies  with  the 
temperature.  According  to  Helmholtz,  this  variation  lies  between 
24.6  and  38.4  m.  per  second  fora  range  of  temperature  between  11° 
and  21°  C.  For  average  room  temperatures  we  may  say  that  in 
the  motor  nerves  of  the  frog  the  impulse  travels  with  a  velocity 
of  28  to  30  meters  per  second.  Similar  experiments  have  been 
made  upon  man  and  other  mammals.  Helmholtz  stimulated 
the  median  nerve  in  man  at  two  different  points  and  recorded 
the  resulting  contractions  of  the  muscles  of  the  thumb.  By 
this  means  he  obtained  an  average  velocity  of  34  m.  per -second, 
but  others,  making  use  of  the  same  method,  have  reported 
varying  results.  Piper*  has  applied  the  string-galvanometer 
to  the  investigation  of  this  point.  Using  the  unipolar  method, 
he  stimulated  the  median  nerve  with  induction  shocks,  the  active 
electrode  being  applied  at  the  elbow  and  at  the  axilla  at  a  distance 
apart  of  from  160  to  170  mm.  The  muscular  response  was 
recorded  not  by  registering  the  contraction,  but  by  means  of  its 
action  current.  When  the  stimulus  was  applied  at  the  elbow  the 
interval  between  the  stimulation  and  the  electrical  response 
averaged  0.00442  second;  at  the  axilla  the  interval  was  0.00578 
second.  The  difference,  namely,  0.00136  second,  gave  the  time 
necessary  for  the  impulse  to  travel  over  160  to  170  mm.  of  nerve, 
and  indicated  a  velocity  of  117  to  125  m.  per  second. 

It  is  interesting  to  recall  that  only  six  years  before  Helmholtz's  first  pub- 
lication Johannes  Miiller  had  stated  that  we  should  never  find  a  means  of 
determining  the  velocity  of  the  nerve  impulse,  since  it  would  be  impossible 
to  compare  points  at  great  distances  apart,  as  in  the  case  of  the  movement 
of  light.  "  The  time,"  said  he,  "  required  for  the  transmission  of  a  sensation 
from  the  periphery  to  the  brain  and  the  return  reflex  movements  of  the  mus- 
cles is  infinitely  small  and  unmeasurable."  The  mode  of  reasoning  by  which 
Helmholtz  was  led  to  doubt  the  validity  of  this  assertion  is  interesting.  He 
says  ("  Miiller's  Archiv,"  1852,  330) :  "  As  long  as  physiologists  thought  it 
necessary  to  refer  nerve  actions  to  the  movement  of  an  imponderable  or 
psychical  principle,  it  must  have  appeared  incredible  that  the  velocity  of  this 
movement  could  be  measured  within  the  short  distances  of  the  animal  body. 
At  present  we  know  from  the  researches  of  du  Bois-Reymond  upon  the  electro- 
motive properties  of  nerves  that  those  activities  by  means  of  which  the  con- 
duction of  an  excitation  is  accomplished  are  in  reality  actually  conditioned 
by,  or  at  least  closely  connected  with  an  altered  arrangement  of  their  material 
particles.  Therefore  conduction  in  nerves  must  belong  to  the  series  of  self- 
propagating  reactions  of  ^ponderable  bodies,  such,  for  example,  as  the  con- 
duction of  sound  in  the  air  or  elastic  structures,  or  the  combustions  in  a  tube 
filled  with  an  explosive  mixture."  One  of  the  first  fruits,  therefore,  of  the 
scientific  investigation  of  the  electrical  prof>erties  of  the  nerve  fiber  was  the 
discovery  of  the  important  fact  of  the  velocity  of  the  nerve  impulse. 

*  Piper,  "Archiv  f.  d.  ges.  Physiologic,"  1908,  124,  591. 


112  THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 

Numerous  efforts  have  been  made  to  determine  the  velocity 
of  the  nerve  impulse  in  medullated  sensory  fibers.  The  results 
have  not  been  entirely  satisfactory.  The  end-organ  hi  this  case  is 
the  cortex  of  the  cerebrum,  and  its  reaction  consists  in  arousing  a 
sensation,  or  a  reflex  action.  Neither  end-reaction  can  be  meas- 
ured directly.  Attempts  have  been  made  to  determine  it  indi- 
rectly by  noting  the  tune  of  a  voluntary  muscle  response  for  sensory 
stimuli  applied  to  the  skin  at  different  distances  from  the  spinal 
axis.  In  such  cases  the  sensory  impulse  travels  to  the  cord,  thence 
to  the  brain,  and  the  return  motor  impulse  travels  from  brain  to 
cord  and  then  by  the  motor  nerves  to  the  muscle  used  for  the  re- 
sponse. The  results  of  this  method  have  been  discordant,  owing 
probably  to  the  fact  that  the  central  paths  from  two  different  points 
on  the  skin  are  not  identical.  It  is  usually  assumed — without, 
however,  very  convincing  proof — that  the  velocity  of  the  impulse 
in  the  medullated  afferent  nerve  fibers  is  the  same  as  in  the 
efferent  fibers.  A  large  number  of  observations  are  on  record 
which  show  that  the  velocity  varies  greatly  in  the  nerves  of 
different  animals.  In  the  mammal,  according  to  Chauveau,  the 
velocity  for  the  non-medullated  fibers  is  only  8  meters  per  second; 
in  the  lobster  it  is  6  meters  per  second;  in  the  octopus,  2  meters; 
in  the  olfactory  (sensory)  nerve  of  the  pike,  £  meter,  and  in  the 
anodon,  only  -j-J-0-  meter  per  second. 

Relation  of  the  Nerve  Impulse  to  the  Wave  of  Negativity. — 
A  fact  of  great  significance  is  that  the  velocity  of  the  impulse  in  the 
motor  nerves  of  the  frog  corresponds  exactly  to  the  velocity  of  the 
wave  of  negativity  as  measured  by  Bernstein.  Evidently  the  two 
phenomena  are  coincident  in  their  progress  along  the  fiber,  and 
physiologists  generally  have  accepted  the  existence  of  an  action  cur- 
rent as  a  proof  of  the  passage  of  a  nerve  impulse.  This  belief  is 
strengthened  by  the  fact  that,  as  stated  above,  the  negative  wave  ac- 
companies the  nerve  impulse  not  only  when  the  nerve  is  stimulated 
by  electrical  currents,  but  also  after  mechanical,  chemical,  or  reflex 
stimulation.  The  question  has  been  raised  as  to  whether  this  elec- 
trical phenomenon  accompanies  the  normal  nerve  impulse, — that  is, 
the  nerve  impulse  that  originates  in  the  nerve  centers,  in  the  case 
of  motor  nerves,  or  in  the  peripheral  sense  organs  in  the  case  of  sen- 
sory nerves.  In  regard  to  the  latter  relation  we  have  positive  evi- 
dence that  when  light  falls  upon  the  living  retina  an  electrical  distur- 
bance is  produced  by  the  visible  rays  of  the  spectrum,*  and  there 
is  every  reason  to  believe  that  the  passage  of  visual  impulses  along 
the  optic  nerve  is  accompanied  by  an  electrical  change.  With 
regard  to  normal  motor  impulses,  the  evidence  is  also  positive  that 
motor  discharges  from  the  central  nervous  system  are  accompanied 

*  See  Einthoven  and  Jolly,  "Quarterly  Journal  of  Experimental  Physiol- 
ogy," 1,  373,  1908. 


NATURE  OF  THE  NERVE  IMPULSE.  113 

by  a  wave  of  electrical  potential.  This  fact  may  be  shown  by 
stimulating  the  motor  areas  in  the  cerebral  cortex  and  testing  the 
efferent  nerves,  such  as  the  sciatic,  for  an  action  current;  or  by 
stimulating  a  posterior  root  on  one  side  in  the  lumbar  region  and 
testing  the  sciatic  nerve  on  the  other  side  with  a  galvanometer.* 
Moreover,  all  influences  that  alter  the  velocity  or  strength  of  the 
nerve  impulse  affect  the  intensity  of  the  action  current  in  the  same 
manner.  It  is  believed  generally,  therefore,  that  the  electrical 
change  is  an  invariable  accompaniment  of  the  excitatory  wave, 
and  the  demonstration  of  an  action  current  in  a  nerve  is  tanta- 
mount to  a  proof  of  the  passage  of  a  nerve  impulse,  f 

Direction  of  Conduction  in  the  Nerve. — The  fact  that  under 
normal  conditions  the  motor  fibers  conduct  impulses  only  in  one 
direction — i.  e.,  toward  the  periphery — and  the  sensory  fibers  in 
the  opposite  direction — that  is,  toward  the  nerve  center — suggests, 
of  course,  the  question  as  to  whether  the  direction  of  conduction  is 
conditioned  by  a  fundamental  difference  in  structure  in  the  two 
kinds  of  fibers.  No  such  difference  in  structure  has  been  revealed 
by  the  microscope.  It  is  the  accepted  belief  in  physiology  that 
any  nerve  fiber  may  conduct  an  impulse  in  both  directions,  and 
does  so  conduct  its  impulses  when  the  fiber  is  stimulated  in  the 
middle  of  its  course.  An  entirely  satisfactory  proof  for  this 
belief  is  difficult  to  furnish  unless  the  conclusion  in  the  preceding 


Fig.  52.— Schema  to  show  the  arrangement  for  proving  the  propagation  of  the  negative 
charge  in  both  directions:  a,  The  stimulating  electrodes;  g  and  g',  galvanometers  with  leading 
off  electrodes  arranged  to  show  the  negative  variation  on  each  side. 

paragraph  is  admitted — the  conclusion,  namely,  that  the  electrical 
change  is  a  necessary  and  invariable  accompaniment  of  the  nerve 
impulse.  It  is  not  difficult  to  show  by  means  of  a  galvanometer 
that  when  a  nerve  trunk  is  stimulated  the  wave  of  negativity 
spreads  in  both  directions  from  the  point  stimulated  and  gives 
an  action  current  on  either  side,  as  indicated  in  the  accompany- 
ing diagram.  This  fact  holds  true  for  motor  or  for  sensory 
fibers.  The  older  physiologists  attempted  to  settle  this  question 

*Gotch  and  Horsley,  "Phil.  Trans.  Royal  Soc.,"  London,  1891,  vol. 
182,  (B),  and  Boruttau,  "  Pfliiger's  Archiv,"  1901. 

t  For  a  more  extended  discussion,  see  Keith-Lucas,  Croonian  Lecture, 
"  Proceedings  of  the  Royal  Society,"  B.  85,  582,  1912. 


114  THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 

in  a  more  direct  way,  but  by  methods  which  later  experiments 
have  proved  to  be  insufficient.  They  attempted,  for  instance,  to 
unite  a  motor  and  sensory  trunk  directly,  to  cut  the  hypoglossal 
(motor)  and  the  lingual  (sensory)  and  suture,  say,  the  central  stump 
of  the  lingual  to  the  peripheral  stump  of  the  hypoglossal.  If  stimu- 
lation of  this  latter  trunk,  after  union  had  been  established,  gave 
signs  of  sensation  it  was  considered  as  proof  that  the  efferent  hypo- 
glossal  fibers  were  now  conducting  afferently.  We  now  know  that  in 
such  a  case  the  old  hypoglossal  fibers  degenerate  completely,  and 
the  new  ones  that  are  eventually  formed  in  their  place  are  out- 
growths from  the  lingual  stump,  or  at  least  are  not  the  old  efferent 
fibers,  and  hence  experiments  of  this  kind  are  not  so  conclusive 
as  they  seemed  to  be  at  the  time  when  it  was  supposed  that  severed 
nerve  fibers  can  unite  immediately,  by  first  intention,  without 
previous  degeneration.  A  similar  objection  applies  to  Paul  Bert's 
often  quoted  experiment.  Bert  implanted  the  tip  of  a  rat's  tail 
into  the  skin  of  its  back.  After  union  had  taken  place  the  tail 
was  severed  at  the  base,  and  the  stump  now  attached  to  the  back 
was  tested  from  time  to  time  as  to  its  sensibility.  Sensation 
returned  slowly.  At  first  it  was  indefinite,  but  by  the  end  of  a 
year  was  apparently  normal. 

Modification  of  the  Nerve  Impulse  by  Various  Influences — 
Narcosis — Temperature. — The  strength  of  the  impulse  and  its 
velocity  may  be  modified  in  various  ways:  by  the  action  of 
temperature,  narcotics,  pressure,  etc.  Variations  of  tempera- 
ture, as  stated  before,  change  the  velocity  of  propagation  of  the 
impulse,  the  velocity  increasing  with  a  rise  of  temperature  up 
to  a  certain  point.  So  also  the  irritability  as  well  as  the  con- 
ductivity of  the  nerve  fiber  is  influenced  markedly  by  tem- 
perature. If  a  small  area  of  a  nerve  trunk  be  cooled  or  heated, 
the  nerve  impulse  as  it  passes  through  this  area  may  be  increased 
or  decreased  in  strength  or  may  be  blocked  entirely.  Different 
fibers  show  somewhat  different  reactions  in  this  respect;  but, 
speaking  generally,  the  limits  of  conductivity  in  relation  to 
temperature  lie  between  0°  C.  and  50°  C.  Cooling  a  nerve  to 
0°  C.  will  in  most  cases  suspend  the  conductivity,  but  this 
function  returns  promptly  upon  warming.*  By  this  means 
we  can  block  the  nerve  impulses  in  a  nerve  trunk  for  any  desired 
length  of  time.  The  exact  relationship  between  the  temperature 
of  the  nerve  and  the  velocity  of  the  impulse  has  been  studied 
carefully  with  the  object  of  determining  the  temperature  coeffi- 
cient. It  has  been  shown  by  van't  Hoff  that  the  velocity  of 
chemical  reactions  is  increased  twofold  or  more  for  each  rise  of 
10  degrees  in  temperature,  that  is,  the  temperature  coefficient 
*  Howell,  Budgett,  and  Leonard,  "  Journal  of  Physiology,"  16,  298,  1894. 


NATURE  OF  THE  NERVE  IMPULSE.  115 

for  chemical  reactions  lies  between  2  and  3.  On  the  other  hand, 
with  most  physical  processes  the  temperature  coefficient  for  the 
same  range  of  temperature  lies  around  1  or  between  1  and 
2.  Snyder*  finds,  on  comparing  the  velocities  of  the  impulse 
at  different  temperatures,  that  they  follow  van't  Hoff's  law  for 
chemical  reactions,  that  is,  the  velocity  is  approximately  doubled 
by  a  rise  of  10°  C.  in  temperature  within  physiological  limits, 

i  •  velocity  at  Tn  >  10  mi.  • 

or.  expressed  in  more  general  terms,  — -. — r-^     .  V     —  =  2.     This 

'  velocity  at  Tn 

effect  of  temperature  on  the  velocity  of  the  impulse  is  shown 
graphically  in  Fig.  53.  Anesthetics  and  narcotics,!  such  as  ether, 


Fig.  53. — Figure  to  show  the  effect  of  temperature  on  the  velocity  of  the  nerve  impulse. 
At  each  temperature  two  contractions  of  the  gastrocnemius  were  recorded,  one  when  the 
nerve  was  stimulated  close  to  tne  muscle,  one  when  it  was  stimulated  further  away  (44  mm.). 
The  horizontal  distance  between  the  curves  as  they  rise  can  be  expressed  in  time  by  refer- 
ence to  the  tuning-fork  vibrations  (200  per  second)  given  below.  For  intervals  of  10°  C. 
it  will  be  seen  that  the  velocity,  as  indicated  by  the  reciprocals  of  the  distances  between 
the  pairs  of  curves,  indicates  a  coefficient  of  two. — (Snyder.) 

chloroform,  cocain,  chloral,  phenol,  alcohol,  etc.,  may  be  applied 
locally  to  a  nerve  trunk,  and  if  the  application  is  made  with  care 
the  conductivity  and  irritability  may  be  lessened  or  suspended 
entirely  at  that  point,  to  be  restored  again  when  the  narcotic 
is  removed.  It  is  an  interesting  fact  that  the  conductivity  of 
the  nerve  may  be  suspended  also  by  deprivation  of  oxygen,J — 
that  is,  by  local  suffocation  or  asphyxia.  A  nerve  fiber  sur- 
rounded by  an  oxygen-free  atmosphere  will  slowly  lose  its 
conductivity,  and  this  property  will  be  restored  promptly  upon 
the  admission  of  oxygen.  Compression  of  a  nerve  will  also 
suspend  its  conductivity  without  permanently  injuring  the 
libers,  provided  the  pressure  is  properly  graduated.  Lastly, 
as  was  explained  in  a  preceding  chapter,  the  conductivity  of  the 
nerve  may  be  increased  or  decreased  or  suspended  entirely  by  the 

*  Snyder,  "American  Journal  of  Physiology,"  22,  179,  1908 
t  Frohlich,  "Zeitschrift  f.  allgemeine  Physiol.  "  3,  75,  1903 
J  Baeyers,  ibid.,  2,  169,  1903. 


116  THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 

action  of  a  galvanic  (polarizing)  current.  This  method  of  sus- 
pending conductivity  temporarily  has  been  frequently  employed 
for  experimental  purposes,  the  arrangement  being  as  represented 
in  Fig.  54. 

The  Refractory  Period. — In  the  case  of  the  heart,  the  nerve 
cell,  and  the  muscle  it  has  been  shown  that  for  a  short  period  after 
the  tissue  enters  into  a  condition  of  functional  activity  it  is  non- 
irritable  toward  a  second  stimulus.  This  condition  of  loss  of 
excitability  following  upon  or  accompanying  functional  activity 
is  designated  as  the  refractory  period.  It  is  interesting  to  find  that 
a  tissue  so  irritable  as  a  nerve  fiber  exhibits  the  same  phenomenon. 
For  a  very  brief  period  (0.002  to  0.006  of  a  second),  after  it  enters 
into  action,  as  indicated  by  the  electrical  response,  a  second 
stimulus  throw  in  will  be  found  to  be  ineffective.  As  the  elec- 
trical change  passes  off,  that  is,  as  the  state  of  activity  subsides, 
the  nerve  regains  its  normal  irritability.  The  refractory  period 
of  the  nerve  fiber  may  be  much  prolonged  by  conditions  which  slow 
the  processes  underlying  activity,  for  example,  by  low  tempera- 
tures, or  by  the  action  of  certain  drugs,  such  as  yohimbine  (Tait). 
The  Question  of  Fatigue  of  Nerve  Fibers. — An  important 
question  in  connection  with  the  nature  of  the  nerve  impulse  has 


Fig.  54. — Schema  to  show  the  method  of  blocking  the  nerve  impure  by  means  of  a  polar- 
izing current:  a,  The  stimulating  electrodes;  6,  the  battery,  the  current  of  which  is  led  into  the 
nerve.  The  depressed  irritability  at  both  anode,  +,  and  cathode,  — ,  prevents  the  nerve  im- 
pulse started  at  a  from  reaching  the  muscle. 

been  that  of  the  susceptibility  of  the  nerve  fibers  to  fatigue.  The 
obvious  fatigue  of  muscles  and  of  nerve  centers  has  been  referred  to 
the  accumulation  of  the  products  of  metabolism  of  their  tissues  or 
to  the  actual  consumption  of  the  energy-yielding  material  in  them. 
Funtional  activity  in  these  tissues  implies  the  breaking  down 
of  complex  organic  material  (catabolism)  and  the  setting  free 
of  the  so-called  chemical  energy.  The  internal  energy  of  the 
compound  is  liberated  as  kinetic  energy  of  heat,  etc.  It  has 
been  accepted,  therefore,  that  if  the  nerve  fiber  could  be  dem- 
onstrated to  show  fatigue  as  a  result  of  functional  activity, 
this  fact  would  be  probable  proof  that  the  conduction  of  the  im- 


NATURE    OF    THE    NERVE    IMPULSE.  117 

pulse  is  associated  with  a  chemical  change  of  a  catabolic  nature  in 
the  substance  of  the  fiber.  Experimental  work,  however,  has 
shown  that  under  normal  conditions  the  nerve  fiber  shows  no 
fatigue.  The  experiments  made  upon  this  point  have  been  nu- 
merous and  varied.  The  general  idea  underlying  all  of  them  has 
been  to  stimulate  the  nerve  continuously,  but  to  interpose  a  block 
somewhere  along  the  course  of  the  nerve  so  that  the  impulses  should 
not  reach  the  end-organ.  This  precaution  is  necessary  because 
the  end-organ — muscle,  gland,  etc. — is  subject  to  fatigue,  and 
must  therefore  be  protected  from  constant  activity.  From  time 
to  time  or  at  the  end  of  a  long  period  of  stimulation  the  block  is 
removed  and  it  is  noted  whether  or  not  the  end-organ — for  in- 
stance, the  muscle — gives  signs  of  a  stimulation.  The  removable 
block  has  been  obtained  by  the  action  of  a  polarizing  current,  by 
cold,  by  narcotics,  by  curare,  etc.  Using  curare,  for  instance, 
Bowditch*  found  that  the  sciatic  nerve  might  be  stimulated  continu- 
ously by  induction  shocks  for  several  (four  to  five)  hours  without 
complete  fatigue,  since  as  the  curare  effect  wore  off  the  muscle 
whose  contractions  were  being  recorded  (M.  tibialis  ant.)  began 
to  respond,  at  first  with  single  and  finally  with  tetanic  contractions. 
The  curare  in  this  case  may  be  supposed  to  have  blocked  the  nerve 
impulse  at  the  motor  end-plate  and  thus  protected  the  muscle 
from  responding  until  the  lapse  of  several  hours,  although  the 
nerve  was  under  stimulation  during  this  entire  time.  This 
experiment  has  since  been  repeated  by  Durig,f  who  has  made  use 
cf  the  fact  that  the  effects  of  curare  can  be  removed  within  a  few 
minutes  by  the  salicylate  of  physostigmin.  Durig  stimulated  the 
nerve  for  as  much  as  ten  hours  and  then  upon  removing  the  curare 
block  found  from  the  contraction  of  the  muscle  that  the  nerve 
was  still  conducting.  EdesJ  and  others  have  shown  that  the 
same  result  is  obtained  when  the  nerve  is  tested  by  a  capillary 
electrometer  instead  of  by  the  response  of  an  end-organ.  Under 
such  conditions  the  nerve  exhibits  an  undiminished  action  cur- 
rent, although  constantly  stimulated  by  tetanizing  shocks  from  an 
induction  apparatus.  Brodie  and  Halliburton  §  have  found  that 
the  non-medullated  fibers  in  the  splenic  nerve  can  also  be  stimulated 
for  many  hours  without  losing  their  power  of  conduction, — that 
is,  without  showing  fatigue.  Many  other  observers  have  obtained 
similar  results,  which  have  confirmed  physiologists  in  the  belief 
that  the  nerve  fibers  may  conduct  impulses  indefinitely,  or,  in 
other  words,  that  their  normal  functional  activity  may  be  carried 

*  Bowditch,  "Journal  of  Physiology,"  6,  133, 1885. 

t  Durig,  "Centralblatt  f.  Physiol.,"  15,  751,  1902. 

t  Edes,  "Journal  of  Physiology,"  13,  431,  1892. 

§  Brodie  and  Halliburton,  "Journal  of  Physiology,"  28,  181,  1902. 


118  THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 

on  continuously  without  fatigue.  If  this  belief  is  entirely  correct 
it  would  place  the  nerve  fibers  in  a  class  by  themselves,  since  all 
other  tissues  that  have  been  studied  show  evidence  of  fatigue  when 
kept  in  continuous  functional  activity.  Moreover,  if  this  belief  is 
entirely  correct  it  would  imply  that  the  conduction  of  an  impulse 
in  the  nerve  fiber  is  not  associated  with  a  consumption  of  material, 
a  metabolism,  and  in  this  respect  also  the  functional  activity  01 
the  nerve  would  be  placed  in  contrast  with  that  of  other  organs. 
It  must  be  remembered,  however,  that,  although  the  above  ex- 
periments demonstrate  the  practical  "  unfatigueableness  "  of 
nerve  fibers  under  ordinary  conditions  of  stimulation,  there  are 
some  reasons  to  make  us  hesitate  in  supposing  that  in  these 
structures  functional  activity  is  entirely  without  a  depressing 
effect  upon  irritability.  Garten  has  shown  that  one  nerve,  the 
olfactory  of  the  pike,  when  stimulated  by  induction  shocks,  with 
an  interval  between  the  stimuli  of  as  much  as  0.27  sec.,  gives 
evidence  of  fatigue,  since  its  .action  current,  as  measured  by  the 
capillary  electrometer,  diminishes  in  extent  quite  rapidly,  and 
recovers  after  a  short  rest.*  So  also  it  has  been  found  that  while 
a  nerve  deprived  of  oxygen,  by  keeping  it  in  an  atmosphere  of 
nitrogen,  loses  its  irritability  after  a  certain  time,  this  event  occurs 
much  more  rapidly  if  the  nerve  is  stimulated  constantly,  f  This 
fact  would  suggest  that  some  oxygen  is  consumed  during  functional 
activity,  and  that  the  ability  of  the  nerve  under  normal  circum- 
stances to  escape  the  results  of  fatigue  may  be  due  possibly  to  the 
fact  that  the  supply  of  oxygen  is  sufficiently  abundant  to  oxidize 
promptly  the  fatigue  substances  formed  during  activity. 

Does  the  Nerve  Fiber  Show  Any  Evidence  of  Metabolism 
During  Functional  Activity?  —  The  functional  part  of  a  nerve 
fiber  in  conduction  is  the  axis  cylinder,  and,  indeed,  probably  the 
neurofibrils  in  the  axis  cylinder.  The  mass  of  this  material,  even 
in  a  large  nerve  trunk,  is  small  (about  9  per  cent.),  and  its  chemistry 
is  but  little  known.  The  efforts  that  have  been  made  to  prove  a 
metabolism  in  the  nerve  fiber  during  activity  have  been  directed 
along  the  lines  indicated  by  what  is  known  of  muscle  metabolism. 
In  a  muscle  during  contraction  heat  is  produced,  the  substance  of 
the  muscle  shows  an  acid  reaction,  and  carbon  dioxid  is  formed. 
Efforts  to  show  similar  reactions  in  stimulated  nerves  have  been 
only  partially  successful.  RollestonJ  investigated  the  question  of 
heat  production  with  the  aid  of  a  delicate  bolometer  capable  of  in- 
dicating a  difference  of  temperature  of  -ginnr0  C.  The  frog's  sciatic 


*  Quoted  from  Biedermann,  "Ergebnisse  der  Physiologic,"  vol.  ii,  part  ii, 
p.  129. 

t  Thorner,  "Zeitschrift  f.  allg.  Physiologic,"  8,  530,  1908. 
t  Rolleston,  "Journal  of  Physiology,"  11,  208,  1890. 


NATURE    OF    THE    NERVE    IMPULSE.  119 

was  used,  but  no  increase  in  temperature  during  stimulation  could 
be  demontrated.  Making  use  of  a  more  sensitive  instrument, 
Hill  has  obtained  the  same  negative  result.  If  any  heat  is 
produced  by  the  transmission  of  a  nerve  impulse  it  must  be 
less,  according  to  his  measurements,  than  a  hundred-millionth 
of  a  degree  centigrade.*  On  the  other  hand,  Tashirof  reports 
that,  by  means  of  a  new  method  which  is  capable  of  detecting  as 
little  as  0.0000001  gm.  of  carbon  dioxid,  he  has  been  able  to  show 
that  the  resting  nerve  produces  carbon  dioxid  and  that  this  pro- 
duction is  increased  about  two  and  a  half  times  when  the  nerve  is 
stimulated.  Additional  evidence  for  the  occurrence  of  a  nerve 
metabolism  during  activity  is  found  in  the  .fact,  already  alluded 
to,  that  oxygen  plays  a  part  in  maintaining  the  irritability  of 
nerves.  An  excised  frog's  nerve  loses  its  irritability  in  an  atmos- 
phere deprived  of  oxygen,  and  regains  it  promptly  when  oxygen 
is  again  supplied.  When  stimulated  in  an  atmosphere  free  from 
oxygen  the  nerve  shows  signs  of  fatigue,  while  in  the  presence  of 
oxygen  activity  is  maintained,  one  may  say  indefinitely,  under 
continuous  stimulation.  These  facts  warrant  the  belief  that 
oxygen  is  used  by  the  nerve  during  activity,  and  presumably  it 
is  used  in  this  as  in  the  other  tissues  to  produce  physiological 
oxidations.  Another  fact  which  points  in  the  same  direction 
is  the  high  value  of  the  temperature  coefficient  for  nerve  conduc- 
tion, which  has  been  referred  to  above.  Bearing  these  two 
general  considerations  in  mind,  we  can  hardly  escape  the  con- 
viction that  the  functional  activity  of  the  nerve  fiber  is  connected 
with  a  chemical  reaction  of  some  kind,  most  probably  a  reaction 
in  which  some  material  in  the  nerve  undergoes  oxidation. 

Views  as  to  the  Nature  of  the  Nerve  Impulse. — The  older  con- 
ceptions of  the  nerve  principle,  while  they  varied  in  detail,  were 
based  upon  the  general  idea  that  the  nervous  system  contains  a 
matter  of  a  finer  sort  than  that  visible  to  our  senses.  This  matter 
was  pictured  at  first  as  a  spirit  (animal  spirits) ,  and  later  as  a  mate- 
rial comparable  to  the  luminiferous  ether  or  to  electricity.  Since 
the  discovery  that  the  nerve  impulse  travels  with  a  relatively  slow 
velocity  and  is  accompanied  by  a  demonstrable  change  in  the 
electrical  condition  of  the  nerve,  many  different  views  regarding 
its  nature  have  been  proposed.  In  discussing  the  matter  it  is 
evident  that  two  perhaps  different  phenomena  have  to  be  consid- 
ered, namely,  the  act  of  excitation  by  natural  or  artificial  stimuli 
and  the  act  of  propagation  or  conduction.  Formerly,  it  was  held 

*Hill,  "Journal  of  Physiology,"  43,  433,  1911-12. 

t  Tashiro,  "American  Journal  of  Physiology,"  "Proc.  of  Am.  Physiologi- 
cal Soc.,"  31,  22,  1913. 


120        THE  PHYSIOLOGY  OF  MUSCLE  AND  NERVE. 

in  a  general  way  that  the  nerve  impulse  depends  upon  the  breaking 
down  of  some  unstable  substance  within  the  axis  cylinder.  It  was 
assumed  that  this  sensitive  and  unstable  material  is  upset  by  the 
energy  of  the  stimulus  at  the  point  stimulated,  and  that  the  energy 
thus  liberated  acts  upon  contiguous  particles,  and  so  the  disturb- 
ance is  propagated  along  the  nerve  as  a  progressive  chemical 
change  which  in  a  very  general  way  may  be  compared  to  the  pas- 
sage of  a  spark  along  a  line  of  gunpowder.  A  fundamental  ob- 
jection to  such  a  view  is  the  uncertainty  of  the  proof  regarding  the 
consumption  of  material  in  a  nerve  during  activity,  as  has  been  ex- 
plained in  the  preceding  sections.  Quite  the  opposite  point  of 
view  has  also  been  held,  namely,  the  idea  that  the  nerve  impulse 
is  a  purely  physical  process,  which  involves  no  chemical  change 
and  no  using  up  of  material.  Various  suggestions  have  been 
offered  as  to  the  character  of  this  physical  change,  but  the  one  that 
is  perhaps  most  worthy  of  consideration  identifies  the  nerve  im- 
pulse with  the  negative  electrical  change  that  is  known  to  pass 
along  the  fiber.  It  is  assumed  that  this  electrical  change  consti- 
tutes the  nerve  impulse,  and  to  explain  its  occurrence  and  propaga- 
tion from  a  physical  standpoint  it  has  been  supposed  that  the 
nerve  fiber  has  a  structure  essentially  similar  to  the  "  core  conduc- 
tor "  (see  p.  108),  in  that  it  contains  a  central  thread  surrounded  by 
a  liquid  sheath  of  less  conductive  material.  The  central  thread 
may  be  supposed  to  be  the  axis  cylinder  and  the  less  conductive 
sheath  the  surrounding  myelin,  or,  perhaps,  to  follow  another  sug- 
gestion that  fits  the  non-medullated  as  well  as  the  medullated  fibers, 
the  central  threads  are  represented  by  the  neurofibrils  within  the 
axis  cylinder  and  the  surrounding  sheath  by  the  perifibrillar 
substance.  That  the  axis  cylinder  is  a  better  conductor  than 
the  myclin  sheath  has  been  indicated  by  the  microchemical 
researches  of  Macallum.  This  observer  has  shown  that  in  the 
axis  cylinder  the  chlorids  exist  in  greater  concentration  than  in 
the  surrounding  sheath.*  The  point  of  importance  is  that,  with 
a  core  model  (see  Fig.  50),  consisting  of  a  glass  tube  with  a  core 
of  platinum  wire  and  a  sheath  of  solution  of  sodium  chlorid, 
0.6  per  cent.,  electrical  phenomena  can  be  obtained  similar  to 
those  shown  by  the  stimulated  nerve.  If  an  induction  current, 
serving  as  a  stimulus,  is  sent  into  one  end  of  such  an  artificial 
nerve  and  from  the  other  end  two  leading  off  electrodes  are 
connected  with  a  galvanometer,  then  we  can  demonstrate  by 
means  of  the  galvanometer  that  an  electrical  charge  is  propagated 
along  the  model  at  each  application  of  the  stimulus.  And,  as 
such  a  moving  electrical  disturbance  is  the  only  objective 

*  Macallum,  "  Proceedings  of  the  Royal  Society,"  1906,  B.  Ixxvii,  165. 


NATURE  OF  THE  NERVE  IMPULSE.  121 

phenomenon  known  to  occur  in  the  stimulated  nerve,  it  has  been 
assumed  that  it  constitutes  the  nerve  impulse.  When  this 
electrical  disturbance  reaches  the  end-organ, — the  muscle,  for 
instance, — it  initiates  the  chemical  changes  that  characterize 
the  activity  of  the  organ.  This  kind  of  theory  makes  the  nerve 
impulse  an  electrical  phenomenon,  and  assumes  that  the  nerve 
fibers  have  become  differentiated  to  form  a  specific  kind  of 
conductor,  the  efficiency  of  which  depends  upon  its  having  a 
structure  similar  to  that  of  a  "  core  conductor."  Other  theories 
of  a  physico-chemical  character  have  been  proposed  especially 
to  explain  the  initial  excitation  caused  by  a  stimulus  and  the 
electrical  phenomena  responsible  for  the  action  current.  Nernst 
has  supposed  that  the  electrolytes  contained  in  the  axis  cylinder 
lie  within  membranous  partitions  which  are  impermeable  to  the 
passage  of  certain  ions.  When  an  electrical  current  is  passed 
through  a  nerve,  it  is  conveyed  of  course  by  the  dissociated  elec- 
trolytes, and  in  consequence  of  the  impermeable  character  of  the 
septa,  there  will  be  a  concentration  of  positively  charged  ions  at 
one  face  of  the  membranes  and  of  negatively  charged  ions  at  the 
other.  When  the  concentration  of  the  ions  reaches  a  certain  point, 
excitation  occurs.  The  nature  of  the  excitation  under  such 
circumstances  has  been  further  imagined  by  Hill,  who  suggests 
that  some  sensitive  substance,  presumably  a  colloid,  exists  in  the 
nerve  in  combination  with  certain  ions.  This  combination  is  in 
an  unstable  or  critical  state,  and  when,  in  consequence  of  a  stimulus 
of  any  kind,  the  concentration  of  ions  in  combination  with  it  is 
increased,  it  breaks  down  and  this  act  constitutes  the  excitation, 
which  is  then  propagated  along  the  nerve.  This  author  has 
treated  his  assumption  mathematically  to  ascertain  how  far  it 
accords  with  the  known  facts  of  the  stimulation  of  nerves  with 
electrical  currents.  It  should  be  added  that  these  and,  indeed, 
all  specific  theories  of  the  nature  of  the  nerve  impulse  are,  at 
present,  matters  for  discussion  and  experiment  among  specialists. 
We  are  far  from  having  an  explanation  of  the  nerve  impulse 
resting  upon  such  an  experimental  basis  as  to  command  general 
acceptance.* 

Qualitative  Differences  in  Nerve  Impulses  and  Doctrine  of  Spe- 
cific Nerve  Energies. — Whether  or  not  the  nerve  impulses  in  vari- 


*  For  a  summary  of  the  literature  upon  the  nature  of  the  nerve  impulse 


40,  190,  1910;  Lucas,  ibid.,  p.  224;  and  Croonian  Lecture,  "Proceedings  Royal 
Society,"  B.  85,  582,  1912;  Tashiro,  "Proceedings  of  the  National  Academy  of 
Sciences,"  1,  110,  1915. 


122  THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 

ous  nerve  fibers  differ  in  kind  is  a  question  of  great  interest  in  physi- 
ology. The  usually  accepted  view ,  is  that  they  are  identical  in 
character  in  all  fibers  and  vary  only  in  intensity.  According  to 
this  view,  a  sensory  nerve — the  auditory  nerve,  for  instance — car- 
ries impulses  similar  in  character  to  those  passing  along  a  motor 
nerve,  and  the  reason  that  in  one  case  we  get  a  sensation  of  hearing 
and  in  the  other  a  contraction  of  a  muscle  is  found  in  the  manner 
of  ending  of  the  nerve,  one  terminating  in  a  special  part  of  the  cortex 
of  the  cerebrum,  the  other  in  a  muscle.  From  this  standpoint 
the  nerve  fibers  may  be  compared  to  electrical  wires.  The  current 
conducted  by  the  wires  is  similar  in  all  cases,  but  may  give  rise  to 
very  different  effects  according  to  the  way  in  which  the  wires  ter- 
minate, whether  in  an  explosive  mixture,  an  arc  light,  or  solutions 
of  electrolytes  of  various  kinds.  We  have  in  physiology  what  is 
known  as  the  doctrine  of  specific  nerve  energies,  first  formulated 
by  Johannes  Miiller.  This  doctrine  expresses  the  fact  that  nerve 
fibers  when  stimulated  give  only  one  kind  of  reaction,  whether 
motor  or  sensory,  no  matter  in  what  way  they  may  be  stimulated. 
The  optic  nerve,  for  instance,  gives  us  a  sensation  of  light,  usually 
because  light  waves  fall  on  the  retina  and  thus  stimulate  the  optic 
nerve.  But  if  we  apply  other  forms  of  stimulation  to  the  nerve 
they  will  also,  if  effective,  give  a  sensation  jf  light.  Cutting  the 
optic  nerve  or  stimulating  it  with  electrical  currents  gives  visual 
sensations.  On  the  identity  theory  of  the  nerve  impulses  the 
specific  energies  of  the  various  nerves — that  is,  the  fact  that  each 
gives  only  one  kind  of  response — is  referred  entirely  to  the  charac- 
teristics of  the  tissue  in  which  the  fibers  end.  If,  as  has  been  said, 
one  could  successfully  attach  the  optic  nerve  to  the  ear  and  the 
auditory  nerve  to  the  retina  then  we  should  see  the  thunder  and 
hear  the  lightning. 

The  alternative  theory  supposes  that  nerve  impulses  are  not 
identical  in  different  fibers,  but  vary  in  quality  as  well  as  intensity, 
and  that  the  specific  energies  of  the  various  fibers  depend  in  part  at 
least  on  the  character  of  the  impulses  that  they  transmit.  On 
this  theory  one  might  speak  of  visual  impulses  in  the  optic  nerves 
as  something  different  in  kind  from  the  auditory  impulses  in  the 
auditory  fibers.  With  our  present  methods  of  investigation  the 
question  is  one  that  can  not  be  definitely  decided  by  experimental 
investigation;  most  of  the  discussion  turns  upon  the  applicability 
of  the  doctrine  to  the  explanation  of  various  conscious  reactions 
of  the  sensory  nerves. 

So  far  as  experimental  work  has  been  carried  out  on  efferent 
nerves,  it  is  undoubtedly  in  favor  of  the  identity  theory.  The 
action  current  is  similar  in  all  nerves  examined;  the  reactions  to 


NATURE  OF  THE  NERVE  IMPULSE.  123 

artificial  stimuli  are  essentially  similar.  Moreover,  nerves  of 
one  kind  may  be  sutured  to  nerves  of  another  kind,  and,  after  re- 
generation has  taken  place,  the  reactions  are  found  to  be  deter- 
mined solely  by  the  place  of  ending  (see  p.  81). 

The  Nutritive  Relations  of  the  Nerve  Fiber  and  Nerve  Cell. 
— In  recent  times  in  accordance  with  the  so-called  neuron  doctrine 
(see  p.  129)  every  axis  cylinder  has  been  considered  as  a  process  of 
a  nerve  cell,  and  therefore  as  a  part,  morphologically  speaking,  of 
that  cell.  However  this  may  be,  there  is  excellent  experimental 
evidence  to  show  that  the  physiological  integrity  of  the  axis  cylinder 
depends  upon  its  connection  with  its  corresponding  nerve  cell.  This 
view  dates  from  the  interesting  work  of  Waller,*  who  showed  that 
if  a  nerve  be  severed  the  peripheral  stump,  containing  the  axis  cyl- 
inders that  are  cut  off  from  the  cells,  will  degenerate  in  a  few  days. 
The  process  of  degeneration  brought  about  in  this  way  is  known 
as  secondary  or  Wallerian  degeneration.  The  central  stump,  on 
the  contrary,  remains  intact,  except  for  a  short  region  immediately 
contiguous  to  the  wound,  for  a  relatively  long  period,  extending 
perhaps  over  years.  Waller,  therefore,  spoke  of  the  nerve  cells  as 
forming  the  nutritive  centers  for  the  nerve  fibers,  and  this  belief 
is  generally  accepted.  In  what  way  the  cell  regulates  the  nutrition 
of  the  nerve  fiber  throughout  its  whole  length  is  unknown.  Some  of 
the  cells  in  the  lumbar  spinal  cord,  for  instance,  give  rise  to  fibers  of 
the  sciatic  nerve  which  may  extend  as  far  as  the  foot,  and  yet 
throughout  their  whole  length  the  nutritive  processes  in  these  fibers 
are  dependent  :>n  influences  of  an  unknown  kind,  emanating  from 
the  nerve  cells  to  which  they  are  joined.  These  influences  may 
consist  simply  in  the  effect  of  constant  activity;  that  is,  in  the 
conduction  of  nerve  impulses,  or  there  may  be  some  kind  of  an 
actual  transferal  of  material.  This  latter  idea  is  supported  by  the 
interesting  fact,  which  we  owe  to  Meyer,  that  tetanus  and  diph- 
theria toxins  may  be  transmitted  to  the  central  nervous  system 
by  way  of  the  axis  cylinders  of  the  nerve  fibers.  By  means  of  his 
method  Waller  investigated  the  location  of  the  nutritive  centers 
for  the  motor  and  sensory  fibers  of  the  spinal  nerves.  If  an  anterior 
root  is  cut  the  peripheral  ends  of  the  motor  fibers  degenerate 
throughout  the  length  of  the  nerve,  while  the  fibers  in  the  stump 
attached  to  the  cord  remain  intact;  hence  the  nutritive  centers 
for  the  motor  fibers  must  lie  in  the  cord  itself.  Subsequent  histo- 
logical  work  has  corroborated  this  conclusion  and  shown  that  the 
motor  fibers  of  the  spinal  nerves  take  their  origin  from  nerve  cells 
lying  in  the  anterior  horn  of  gray  matter  in  the  cord,  the  so-called 

*  Waller,   "Mullens  Archiv,"   1852,   p.  392;  and   "Comptes  rendus  de 
1'Acad.  de  la  Science,"  vol.  xxxiv.,  1852. 


124  THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 

motor  or  anterior  root  cells.  If  the  posterior  root  is  cut  between 
the  ganglion  and  the  cord,  the  stump  attached  to  the  cord  degener- 
ates; that  attached  to  the  ganglion  remains  intact,  and  there  is  no 
degeneration  in  the  nerve  peripheral  to  the  ganglion  (Fig.  55).  If, 
however,  this  root  is  severed  peripherally  to  the  ganglion  degenera- 
tion takes  place  only  in  the  spinal  nerve  beyond  the  ganglion.  The 
nutritive  center,  therefore,  for  the  sensory  fibers  must  lie  in  the  pos- 
terior root  ganglion,  and  not  in  the  cord.  This  conclusion  has  also 
been  abundantly  corroborated  by  histological  work.  It  is  known 
that  the  sensory  fibers  arise  from  the  nerve  cells  in  these  ganglia. 
By  the  same  means  it  has  been  shown  that  the  motor  fibers  in  the 
cranial  nerves  arise  from  nerve  cells  (nuclei  of  origin)  situated  in 
the  brain,  while  the  sensory  fibers  of  the  same  nerves,  with  the 
exception  of  the  olfactory  and  optic  nerves  which  form  special  cases, 
arise  from  sensory  ganglia  lying  outside  the  nervous  axis,  such,  for 


Fig.  55. — Diagram  to  show  the  direction  of  degeneration  on  section  of  the  anterior 
and  the  posterior  root,  respectively.     The  degenerated  portion  is  represented  in  black. 

instance,  as  the  spiral  ganglion  of  the  cochlear  nerve,  or  the  gan- 
glion semilunare  (Gasserian  ganglion)  of  the  fifth  cranial  nerve.  . 
Nerve  Degeneration  and  Regeneration. — When  a  nerve 
trunk  is  cut  or  is  killed  at  any  point  by  crushing,  heating,  or  other 
means  all  the  fibers  peripheral  to  the  point  of  injury  undergo  de- 
generation. This  is  an  incontestable  fact,  and  it  is  important  to 
bear  in  mind  the  fact  that  the  definite  changes  included  under 
the  term  degeneration  are  exhibited  only  by  living  fibers.  A 
dead  nerve  or  the  nerves  in  a  dead  animal  show  no  such  changes.* 
The  older  physiologists  thought  that  if  the  severed  ends  of 
the  nerves  were  brought  together  by  sutures  they  might  unite 
by  first  intention  without  degeneration  in  the  peripheral  end. 
We  know  now  that  this  degeneration  is  inevitable  once  the 
living  continuity  of  the  fibers  has  been  interrupted  in 
any  way.  Any  functional  union  that  may  occur  is  a  slow 

*  See  Van  Gehuchten,  "Le  NeVraxe,"  1905,  vii,  203. 


Pig.  56.— Histology  of  a  degenerating  nerve  fiber. 


Pig.  57.— Embryonic  fibers  in  a  regenerating  nerve. 


Kg.  68.~A  newly  developed  fiber  in  a  regenerating  nerve  fiber. 


NATURE    OF   THE    NERVE    IMPULSE.  125 

process  involving  an  act  of  regeneration  of  the  fibers  in  the  peripheral 
stump.  The  time  required  for  the  degeneration  differs  somewhat 
for  the  different  kinds  of  fibers  found  in  the  animal  body.  In  the 
dog  and  in  other  mammalia  the  degeneration  begins  in  a  few  (four) 
days;  in  the  frog  it  may  require  from  thirty  to  one  hundred  and 
forty  days,  depending  upon  the  season  of  the  year,  although  if  the 
frog  is  kept  at  a  high  temperature  (30°  C.)  degeneration  may 
proceed  as  rapidly  as  in  the  mammal.  In  the  dog  it  proceeds  so 
quickly  that  the  process  seems  to  be  simultaneous  throughout  the 
whole  peripheral  stump,  while  in  the  frog,  and,  according  to  Bethe, 
in  the  rabbit,  it  can  be  seen  clearly  that  the  degenerative  changes 
begin  at  the  wound  and  progress  peripherally.  The  fibers  break 
up  into  ellipsoidal  segments  of  myelin,  each  containing  a  piece  of 
the  axis  cylinder,  and  these  segments  in  turn  fragment  very  irregu- 
larly into  smaller  pieces  which  eventually  are  absorbed*  (Fig.  56). 
The  central  stump  whose  fibers  are  still  connected  with  the  nerve 
cells  undergoes  a  similar  degeneration  in  the  area  immediately 
contiguous  to  the  wound,  but  the  degenerative  processes  extend 
for  only  a  short  distance  over  an  area  covering  a  few  internodal 
segments.  Although  the  central  ends  of  the  fibers  remain  sub- 
stantially intact,  it  is  interesting  to  find  that  the  nerve  cells  from 
which  they  originate  undergo  distinct  changes,  which  show  that 
they  are  profoundly  affected  by  the  interruption  of  their  normal 
connections  (see  p.  127).  In  the  peripheral  end  the  process  of 
regeneration  begins  almost  simultaneously  with  the  degenerative 
changes,  the  two  proceeding,  as  it  were,  hand  in  hand.  The  regen- 
eration is  due  to  the  activity  of  the  nuclei  of  the  neurilemmal  sheath. 
These  nuclei  begin  to  multiply  and  to  form  around  them  a  layer  of 
protoplasm,  so  that  as  the  fragments  of  the  old  fiber  disappear 
their  place  is  taken  by  numerous  nuclei  and  their  surrounding 
cytoplasm.  Eventually  there  is  formed  in  this  way  a  continuous 
strand  of  protoplasm  with  many  nuclei,  and  the  fiber  thus  produced, 
which  has  no  resemblance  in  structure  to  a  normal  nerve  fiber, 
is  described  by  some  authors  as  an  "embryonic  fiber";  by  others 
as  a  "band  fiber"  (Fig.  57).  In  the  adult  animal  the  process  of 
regeneration  stops  at  this  point  unless  an  anatomical  connection 
is  established  with  the  central  stump,  and,  indeed,  such  a  connection 
is  usually  established  unless  special  means  are  taken  to  prevent  it. 
The  central  and  peripheral  stumps  find  each  other  in  a  way  that 
is  often  remarkable,  the  union  being  guided  doubtless  by  intervening 
connective  tissue. 

*See  Howell  and  Huber,  "Journal  of  Physiology,"  13,  335,  1892;  also 
Mott  and  Halliburton,  "  Proceedings  Royal  Society,"  1906,  B.  Ixxviii.,  259, 
and  Cajal,  "  Trabajos  del  laboratorio  de  investigaciones  biologicas  (Univ.  of 
Madrid),"  vol.  4,  119,  1906. 


126  THE    PHYSIOLOGY    OF    MUSCLE    AND    NERVE. 

Forsmanns*  has  emphasized  this  peculiar  attraction,  as  it  were,  be- 
tween the  peripheral  and  the  central  ends,  giving  some  reason  to  believe  that 
it  is  a  case  of  chemotaxis  or  chemotropism.  When  the  ends  of  the  nerves 
were  given  very  unusual  positions  by  means  of  collodium  tubes  into  which 
they  were  inserted  they  managed  to  " find"  each  other.  Moreover,  he  states 
that  a  central  stump,  if  given  an  equal  opportunity  to  grow  into  two  collo- 
dium tubes,  one  containing  liver  and  the  other  brain  tissue,  will  chose  the 
latter,  a  fact  which  would  indicate  some  underlying  chemical  attraction  or 
affinity  in  nerve  tissue  for  nerve  tissue.  A  directive  influence  of  this  kind 
depending  upon  some  property  connected  with  chemical  relationship  is  desig- 
nated as  "  chemotaxis." 

If  the  central  and  peripheral  stumps  are  brought  together  by 
suture  or  grow  together  in  any  way,  then,  under  the  influence  of  the 
central  end,  the  "embryonic  fiber"  gradually  becomes  transformed 
into  a  normal  nerve  fiber,  with  myelin  sheath  and  axis  cylinder 
(Fig.  58) .  It  is  possible  that  this  result  is  due  to  local  processes  in 
the  embryonic  fiber  stimulated  by  nutritive  influences  of  some  kind 
from  the  central  stump,  but  more  probably  there  is  an  actual 
downgrowth  of  the  axis  cylinders  from  the  central  ends.  In 
support  of  this  latter  view,  it  may  be  said  that  the  outgrowth  of  the 
new  axis  cylinders  from  the  old  ones  present  in  the  fibers  of  the 
central  stump  has  been  followed  more  or  less  successfully  by  a 
number  of  histologists. 

Bethef  has  thrown  some  doubt  upon  this  view,  for  he  has  shown  appar- 
ently that  in  young  mammals  (eight  days  to  eight  weeks)  the  regeneration  of 
the  fibers  in  the  peripheral  stump  does  not  stop  at  the  stage  of  "band  fibers," 
but  progresses  until  perfectly  normal  nerve  fibers  are  produced,  even  though 
no  connection  is  made  with  the  central  stump.  It  should  be  added,  however, 
that  the  fibers  so  formed  do  not  persist  indefinitely  unless  they  become  con- 
nected with  the  central  stump.  If  this  connection  fails  to  take  place,  the 
newly  formed  fibers  will  degenerate  after  an  interval  of  some  months.  Still, 
the  fact,  if  true,  that  in  the  young  fiber  the  regeneration  is  complete  seems  to 
indicate  that  the  axis  cylinder  may  arise  independently  of  the  fibers  in  the 
central  stump. 

Whether  or  not  Bethe's  observations  upon  the  autoregeneration  of  the 
axis  cylinders  in  the  severed  nerves  of  young  animals  can  be  accepted  is 
doubtful,  the  balance  of  evidence  at  present  seems  to  indicate  that  what  he 
took  for  autoregenerated  fibers  were  really  fibers  which  grew  into  the  de- 
generated trunk  from  the  surrounding  tissue. 

Degenerative  Changes  in  the  Neuron  on  the  Central  Side 
of  the  Lesion. — According  to  the  Wallerian  law  of  degeneration, 
as  originally  stated,  the  nerve  fiber  on  the  central  side  of  the  injury 
and  the  nerve  cell  itself  do  not  undergo  any  change.  As  a  matter 
of  fact,  the  central  stump  immediately  contiguous  to  the  lesion 
undergoes  typical  degeneration  and  regeneration  similar  to  that 
described  for  the  fibers  of  the  peripheral  stump.  The  immediate 

*  Forsmanns,  "Zeigler's  Beitrage,"  27,  216,  1902. 

t  Bethe,  "  Allgemeine  Anat.  u.  Physiologic  des  Nervensystems,"  1903. 


NATURE  OF  THE  NERVE  IMPULSE.  127 

degenerative  changes  in  the  fibers  in  the  central  stump  were  supposed 
to  extend  back  only  to  the  first  node  of  Ranvier, — to  affect,  there- 
fore, only  the  internodal  segment  actually  injured.  Later  it  was 
found  that  the  degeneration  may  extend  back  over  a  distance  of 
several  internodal  segments.  This  limited  degeneration  on  the 
central  side  must  be  considered  as  traumatic, — that  is,  it  involves 
only  those  portions  directly  injured  by  the  lesion.  The  central 
end  of  the  fiber  in  general  was  supposed  to  remain  intact  as  long 
as  its  cell  of  origin  was  normal.  It  was  thought  at  first  that  after 
simple  section  of  a  nerve  trunk,  in  amputation,  for  instance,  the 
nerve  cells  and  central  stumpfe  remain  normal  throughout  the  life 
of  the  individual!  Dickinson,  however,  in  1869  *  showed  that  in 
amputations  of  long  standing  the  motor  cells  in  the  anterior  horn 
of  the  cord  decrease  in  number  and  the  fibers  in  the  central  stump 
become  atrophied.  This  observation  has  been  corroborated  by 
other  observers,  and  it  is  now  believed  that  after  section  of  a  nerve 
chronic  degenerative  changes  ensue  in  the  course  of  time  in  the 
central  fibers  and  their  cells,  resulting  in  their  permanent  atrophy. 
We  have,  in  such  cases,  what  has  been  called  an  atrophy  from 
disuse.  A  fact  that  has  been  discovered  more  recently  and  that 
is  perhaps  of  more  importance  is  that  the  nerve  cells  do  undergo 
certain  definite  although  usually  temporary  changes  immediately 
after  the  section  of  the  nerve  fibers  arising  from  them.  It  has  been 
shown  that  when  a  nerve  is  cut  the  corresponding  cells  of  origin 
may  show  distinct  histological  changes  within  the  first  twenty-four 
hours.  These  changes  consist  in  a  circumscribed  destruction  of 
the  chromatin  material  in  the  cells  (chromatolysis),  which  in  a 
short  tune  extends  over  the  whole  cell,  so  that  the  primary  staining 
power  of  the  cell  is  lost  (condition  of  achromatosis)  (see  Fig.  63). 
The  cell  also  becomes  swo'llen  and  the  nucleus  may  assume  an 
excentric  position.  These  retrogressive  changes  continue  for  a 
certain  period  (about  eighteen  days).  After  reaching  their  maxi- 
mum of  intensity  the  cells  usually  undergo  a  process  of  restitution 
and  regain  their  normal  appearance,  although  in  some  cases  the 
degeneration  is  permanent.  According  to  other  observers  a  number 
of  the  cells  in  the  spinal  cord  and  spinal  ganglia  undergo  simple 
atrophy  after  section  of  their  corresponding  nerves,  and  some  of 
the  nerve  fibers  in  the  central  stumps  may  also  show  atrophy, 
while  others  undergo  a  genuine  degeneration,  which,  however, 
comes  on  much  later  than  in  the  peripheral  stumps.  It  seems 
evident  that  the  behavior  of  the  cells  and  fibers  on  the  central  side 
of  the  section  is  not  uniform;  atrophy  rather  than  degeneration  is 
the  change  that  is  prominent,  and  this  atrophy  in  some  neurons 
occurs  early,  while  in  others  it  is  apparent  only  after  a  long 
*  "  Journal  of  Anatomy  and  Physiology,"  3,  176,  1869. 


128  THE    PHYSIOLOGY    OF   MUSCLE    AND    NERVE. 

interval  of  time.  An  explanation  of  this  variation  in  the  re- 
action of  the  nerve  cells  and  their  disconnected  central  stumps 
cannot  yet  be  given.  On  the  peripheral  side  of  the  section,  as 
stated  above,  the  degenerative  changes  are  complete  and  affect 
all  of  the  fibers.* 

*Nissl,  "Allgemeine  Zeitschrift  f.  Psychiatric,"  48,  197,  1892.  Also 
Bethe,  loc.  tit.,  and  Ranson,  "  Retrograde  Degeneration  in  the  Spinal  Nerves," 
The  Journal  of  Comparative  Neurology  and  Psychology,  1906,  xvi,  265. 


SECTION  II. 

THE  PHYSIOLOGY  OF  THE  CENTRAL 
NERVOUS  SYSTEM. 


CHAPTER  VI. 

STRUCTURE  AND  GENERAL  PROPERTIES  OF  THE 
NERVE  CELL. 

The  Neuron  Doctrine. — Since  the  last  decade  of.the  nineteenth 
century  the  physiology  of  the  nervous  system  has  been  treated 
from  the  standpoint  of  the  neuron.  According  to  this  point  of 
view,  the  entire  nervous  system  is  made  up  of  a  series  of  units, 
the  neurons,  which  are  not  anatomically  continuous  with  each 
other,  but  communicate  by  contact  only.  It  has  been  taught  also 
that  each  neuron  represents  from  an  anatomical  and  physiological 
standpoint  a  single  nerve  cell.  The  typical  neuron  consists  of 
a  cell  body  with  short,  branching  processes,  the  dendrites,  and  a 
single  axis  cylinder  process,  the  axon  or  axite,  which  becomes  a 
nerve  fiber,  acquiring  its  myelin  sheath  at  some  distance  from  the 
cell.  According  to  this  view,  the  peripheral  nerve  fibers  are  simply 
long  processes  from  nerve  cells.  Within  the  central  nervous  system 
each  neuron  connects  with  others  according  to  a  certain  schema. 
The  axon  of  each  neuron  ends  in  a  more  or  less  branched  "  terminal 
arborization,"  forming  a  sort  of  end-plate  which  lies  in  contact 
with  the  dendrites  of  another  neuron,  or  in  some  cases  with  the 
body  of  the  cell  itself,  the  essentially  modern  point  of  view  being 
that  where  the  terminal  arborization  of  the  axon  meets  the  dendrites 
or  body  of  another  neuron  the  communication  is  by  contact,  the 
neurons  being  anatomically  independent  units.  It  is  usually  ac- 
cepted also  as  a  part  of  the  neuron  doctrine  that  the  conduction 
of  a  nerve  impulse  through  a  neuron  is  always  in  one  direction, 
that  the  dendrites  are  receiving  organs,  so  to  speak,  receiving  a 
stimulus  or  impulse  from  the  axon  of  another  unit  and  conveying 
this  impulse  toward  the  cell  body,  while  the  axon  is  a  discharging 
9  129 


130 


PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 


process  through  which  an  impulse  is  sent  out  from  the  cell  to 
reach  another  neuron  or  a  cell  of  some  other  tissue.  The  neuron, 
so  far  as  conduction  is  concerned,  shows  a  definite  polarity, 
the  conduction  in  the  dendrites  being  cellulipetal,  in  the  axons, 
cellulifugal. 

The  neuron  doctrine,  so  far  as  the  name  at  least  is  concerned,  dates  from 
a  general  paper  by  Waldeyer,*  in  which  the  newer  work  up  to  that  time  was 
summarized.  The  main  facts  upon  which  the  conception  rests  were  furnished 
by  His  (1886),  to  whom  we  owe  the  generally  accepted  belief  that  the  nerve 
fiber  (axis  cylinder)  is  an  outgrowth  from  the  cell,  and  secondly  by  Golgi, 
Cajal,  and  a  host  of  other  workers,  who,  by  means  of  the  new  method  of  Golgi, 
demonstrated  the  wealth  of  branches  of  the  nerve  cells,  particularly  of  the 
dendrites,  and  the  mode  of  connection  of  one  nerve  unit  with  another.  The 
view  that,  these  units  are  anatomically  independent  and  on  the  embryological 


Fig.  59. — Moto~  cell,  anterior  horn  of  gray  matter  of  cord.     From  human  fetus  (Lenhos- 
ae/c):    *  marks  the  axon;    the  other  branches  are  dendrites. 


side  are  derived  each  from  a  single  epiblastic  cell  (neuroblast)  has  proved 
acceptable  and  most  helpful;  but  the  validity  of  this  hypothesis  has  been 
called  into  question  from  time  to  time.  Some  histologists — Apdthy,  Bethe, 
Nissl — have  attacked  the  most  fundamental  feature  of  the  neuron  doctrine — 
the  view,  namely,  that  each  neuron  represents  an  independent  anatomical 
element.  These  authors  contend  that  the  neurofibrils  of  the  axis  cylinder 
pass  through  the  nerve  cells  and  enter  by  way  of  a  network  into  direct  connec- 

*"Deut.  med.  Wochenschrift,"  1891,  p.  50. 


PROPERTIES    OF   THE    NERVE    CELL.  131 

tion  with  the  neurofibrils  of  other  neurons  (see  Fig.  64).  The  neurofibrils  form 
a  continuum  through  which  nerve  impulses  pass  without  a  break  from  neuron 
to  neuron.  According  to  this  conception,  the  ganglion  cells  play  no  direct 
part  in  the  conduction  of  the  impulse  from  one  part  of  the  nervous  system  to 
another;  the  neurofibrils  alone,  and  the  intracellular  and  pericellular  networks 
with  which  they  connect,  form  the  conducting  paths  that  are  everywhere  in 
continuity.  In  the  explanation  given  below  of  the  activities  of  the  nervous 
system,  the  author,  following  the  usual  custom,  makes  use  of  the  neuron 
doctrine. 

The  Varieties  of  Neurons. — The  neurons  differ  greatly  in 
size,  shape,  and  internal  structure,  and  it  is  impossible  to  classify 
them  with  entire  success  from  either  a  physiological  or  an  anatomical 
standpoint.  Neglecting  the  unusual  forms  whose  occurrence  is 
limited  and  whose  structure  is  perhaps  incompletely  known,  there 
are  three  distinct  types  whose  form  and  structure  throw  some 
light  on  their  functional  significance: 

I.  The  bipolar  cells.  This  cell  is  found  in  the  dorsal  root  gan- 
glia of  the  spinal  nerves  and  in  the  ganglia  attached  to  the  sensory 
fibers  of  the  cranial  nerves,  the  ganglion  semilunare  (Gasserian) 
for  the  fifth  cranial,  the  g.  geniculi  for  the  seventh,  the  g.  vestibu- 
lare  and  g.  spirale  for  the  eighth,  the  g.  superius  and  g.  petrosum 
for  the  ninth,  the  g.  jugulare  and  g.  nodosum  for  the  tenth. 

The  typical  cell  of  this  group  is  found  in  the  dorsal  root  ganglia. 
In  the  adult  the  two  processes  arise  as  one,  so  that  the  cell  seems  to 
be  unipolar,  but  at  some  distance  from  the  cell  this  process  divides 
in  T,  one  branch  passing  into  the  spinal  cord  via  the  posterior 
root,  the  other  entering  the  spinal  nerve  as  a  sensory  nerve  fiber 
to  be  distributed  to  some  sensory  surface.  Both  processes  become 
medullated  and  form  typical  nerve  fibers.  That  these  apparently 
unipolar  cells  are  really  bipolar  is  shown  not  only  by  this  division 
into  two  distinct  fibers,  but  also  by  a  study  of  their  development 
in  the  embryo.  In  early  embryonic  life  the  two  processes  arise 
from  different  poles  of  the  cell,  and  later  become  fused  into  an  ap- 
parently simple  process  (Fig.  60).  The  striking  characteristics  of 
this  cell,  therefore,  are  that  it  gives  rise  to  two  nerve  fibers,  and  that 
it  possesses  no  dendritic  processes.  On  the  physiological  side  these 
cells  might  be  designated  as  sensory  cells,  since  they  appear  to  be 
associated  always  with  sensory  nerve  fibers. 

The  nerve  cells  found  in  the  sensory  ganglia  exhibit,  as  a  matter  of  fact, 
a  number  of  different  types,  some  of  which  possess  short  dendritic  processes. 
These  histological  variations  cannot  as  yet  be  given  a  physiological  signifi- 
cance, but  their  occurrence  certainly  seems  to  indicate  a  possibility  that 
the  sensory  ganglia  may  have  a  much  more  varied  physiological  activity 
than  has  been  attributed  to  them  heretofore.  For  a  description  of  theso 
ganglia  and  a  classification  of  their  cells  under  eight  different  types  con- 
sult Cajal  in  "Ergebnisse  der  Anat.  u.  Entwickelungsgeschichte,"  vol.  xvi., 
1906,  and  Dogiel,  "Bau  der  Spinalganglien,  etc.,"  Jena,  1908. 


132 


PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 


So  far  as  the  sensory  fibers  of  the  spinal  and  cranial  nerves 
are  concerned,  it  is  worth  noting  also  that  all  of  them  arise  from 
cells  lying  outside  the  main  axis  of  the  central  nervous  system. 
It  has  been  a  question  whether  the  sensory  impulses  brought 
to  the  ganglion  cells  through  the  peripheral  process  (sensory 


Fig.  60. — Bipolar  cells  in  the  posterior  root  ganglion.  Section  through  spinal  gan- 
glion of  newborn  mouse  (Lenhossek) :  a,  The  spinal  ganglion;  6,  the  spinal  cord;  c,  the 
posterior,  d,  the  anterior  root. 

fiber)  pass  into  the  body  of  the  cell  before  going  on  to  the  cord 
or  brain,  or  whether  at  the  junction  of  the  two  processes  they 
simply  pass  on  directly  to  the  cord.  According  to  the  histo- 
logical  structure  there  is  no  apparent  reason  why  an  impulse 
should  not  pass  directly  from  the  peripheral  to  the  central 
process  at  the  junction,  but  whether  or  not  this  really  occurs 
and  the  relation  of  the  ganglion  cell  to  the  conducting  path  are 
questions  that  must  be  left  unsettled  at  present. 

II.  The  multipolar  cells.  The  processes  of  these  cells  fall  into 
two  groups:  the  short  and  branching  dendrites  with  an  inner 
structure  resembling  that  of  the  cell  body,  and  the  axon  or  axis 
cylinder  process  (Fig.  62).  According  to  the  structure  of  this  last 
process,  this  type  may  be  classified  under  two  heads :  Golgi  cells  of 
the  first  and  the  second  type.  The  cells  of  the  first  type  are  charac- 
terized by  the  fact  that  the  axon  leaves  the  central  gray  matter  and 
becomes  a  nerve  fiber.  This  nerve  fiber  within  the  central  nervous 
system  may  give  off  numerous  collaterals,  each  of  which  ends  in  a 
terminal  arborization.  By  this  means  the  neurons  of  this  type 
may  be  brought  into  physiological  connection  with  a  number  of 
other  neurons.  This  kind  of  nerve  cell  is  frequently  described 
as  the  typical  nerve  cell.  Golgi  supposed  that  it  represents  the 


PROPERTIES    OF   THE    NERVE    CELL. 


133 


motor  type  of  cell,  and  this  view  is,  in  a  measure,  borne  out  by 
subsequent  investigation.  The  distinctly  motor  cells  of  the  cen- 
tral nervous  system — such,  for  instance,  as  the  pyramidal  cells 
of  the  cerebral  cortex,  the  anterior  horn  cells  of  the  spinal  cord, 
the  Purkinje  cells  of  the  cere- 
bellum— all  belong  to  this 
type.  But  within  the  nerve 
axis  most  of  the  conduction 
from  neuron  to  neuron, 
along  sensory  as  well  as 
motor  paths,  is  made  with  *• 
the  aid  of  such  structures, 
the  dendrites  being  the  re- 
ceptive or  sensory  organ  and  ^ 
the  axon  the  motor  appara-*  A 
tus. 

The  Golgi  cells  of  the 
second  type  (Fig.  61)  are  rel- 
atively less  numerous  and 
important.  They  are  char- 


Fig.  61. — Golgi  cell  (second  type).  Fig.    62.  — Normal     anterior     horn     cell 

The  axon,  a,  divides  into  a  number  of  (Warringtori) ,  showing  the  Nissl  granules  in  tht? 

fine  branches. — (From  Obersteiner,  after  cell  and  dendrites:  a,  The  axon. 
Andriezen.) 

acterized  by  the  fact  that  the  axon  process  instead  of  forming  a 
nerve  fiber  splits  into  a  great  number  of  branches  within  the 
gray  matter.  Assuming  that  in  such  cells  the  distinction  between 
the  axon  and  the  dendrites  is  well  made  and  that  as  in  the  other 
type  the  dendrites  form  the  receiving  and  the  axon  the  discharg- 
ing apparatus,  these  cells  would  seem  to  have  a  distributive 
function.  The  impulse  that  they  receive  may  be  transmitted  to 


134  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

one  or  many  neurons.     They  are  sometimes  spoken  of  as  inter- 
mediate or  association  cells. 

Internal  Structure  of  the  Nerve  Cell. — Within  the  body  of 
the  nerve  cell  itself  the  striking  features  of  physiological  signifi- 
cance are,  first,  the  arrangement  of  the  neurofibrils,  and,  second,  the 


•--, 

m 

£^r? 

f*,         V. 


Fig.  63. — Anterior  horn  cell  fourteen  days  after  section  of  the  anterior  root  (Warring- 
ton)  :  To  show  the  change  in  the  nucleus  and  the  Nissl  granules,  beginning  chromatolysis. 


presence  of  a  material  in  the  form  of  granules,  rods,  or  masses 
which  stains  readily  with  the  basic  anilin  dyes,  such  as  methylene 
blue,  thionin,  or  toluidin  blue.  This  latter  substance  is  spoken  of 
as  the  "chromophile  substance,"  tigroid,  or  more  frequently  as 
Nissl 's  granules,  after  the  histologist  who  first  studied  it  success- 
fully. These  masses  or  granules  are  found  in  the  dendrites  as  well 
as  in  the  cell,  but  are  absent  from  the  axon  (see  Fig.  62).  Little  is 
known  of  their  composition  or  significance,  but  their  presence  or  ab- 
sence is  in  many  cases  characteristic  of  the  physiological  condition 
of  the  cell.  After  lesions  or  injuries  of  the  neuron  the  material  may 
become  dissolved  and  diffused  through  the  cell  or  may  decrease  in 
amount  or  disappear,  and  it  seems  probable,  therefore,  that  it  repre- 
sents a  store  of  nutritive  material  (Fig.  63).  The  non-staining 
material  of  the  cell,  according  to  most  recent  observers,  contains 
neurofibrils  which  are  continued  out  into  the  processes,  dendrites  as 
well  as  axons.  These  fibrils  may  be  regarded  as  the  conducting 
structure  along  which  passes  the  nerve  impulse.  The  arrangement 
of  these  fibrils  within  the  cell  is  not  completely  known,  the  results 
obtained  varying  with  the  methods  employed.  A  matter  of  far- 
reaching  importance  on  the  physiological  side  is  the  question  of 
the  existence  of  an  extracellular  nervous  network.  Most  recent 
histologists  agree  in  the  belief  that  there  is  a  delicate  network 
surrounding  the  cells  and  their  protoplasmic  processes.  This 
pericellular  net  or  Golgi's  net  is  claimed  by  some  to  be  a  ner- 
vous structure  connecting  with  the  neurofibrils  inside  the  cell 
and  forming  not  only  a  bond  of  union  between  the  neurons,  but 


PROPERTIES    OF    THE    NERVE    CELL.  135 

possibly  also  an  important  intercellular  nervous  structure  that 
may  play  an  important  role  in  the  functions  of  the  nerve  centers. 
This  view  is  represented  schematically  in  Fig.  64.  According  to 
others,  this  network  around  and  outside  the  cells  is  a  supporting 
tissue  simply  that  takes  no  part  in  the  activity  of  the  nerve  units. 


Fig.  64. — Bethe's  schema  to  indicate  the  connections  of  the  pericellular  network; 
Rz,  A  sensory  cell  in  the  posterior  root  ganglion ;  the  fibrils  in  the  branch  that  runs  to  the 
cord  are  indicated  as  connecting  directly  with  the  pericellular  network  of  the  motor  cells, 
Gz. 

General  Physiology  of  the  Nerve  Cell. — Modern  physiologists 
have  considered  the  cell  body  of  the  neuron,  including  the  den- 
drites,  as  the  source  of  the  energy  displayed  by  the  nervous  system, 
and  it  has  been  assumed  that  this  energy  arises  from  chemical 
changes  in  the  nerve  cell,  as  the  energy  liberated  by  the  muscle 
arises  from  or  is  dependent  upon  the  chemical  changes  in  its  sub- 
stance. It  would  follow  from  this  standpoint  that  evidences  of 
chemical  activity  should  be  obtained  from  the  cells  and  that  these 
elements  should  exhibit  the  phenomenon  of  fatigue.  Regarding 
this  latter  point,  it  is  believed  in  physiology  that  the  nerve' cells  do 
show  fatigue.  The  nerve  centers  fatigue  as  the  result  of  continuous 
activity,  as  is  evident  from  our  personal  experience  in  prolonged  in- 
tellectual or  emotional  activity  and  as  is  implied  in  the  necessity  of 
sleep  for  recuperation  and  by  the  rapidity  with  which  functional 
activity  is  lost  on  withdrawal  of  the  blood  supply.  Objectively, 
also,  it  has  been  shown  in  the  ergographic  experiments  (see  p.  50) 
that  the  well-known  fatigue  of  the  neuromuscular  apparatus  pos- 
sibly affects  the  nerve  centers  as  well  as  the  muscle.  Assuming  that 
the  nerve  cells  are  the  effective  agent  in  the  nerve  centers,  such  facts 
indicate  that  they  are  susceptible  to  fatigue  under  what  may  be  des- 
ignated as  the  normal  conditions  of  activity.  But  we  have  no  very 


136  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

direct  proof  that  this  property  is  possessed  universally  by  the  nerve 
cells  nor  any  indication  of  the  probable  differences  in  this  regard 
shown  by  nerve  cells  in  different  parts  of  the  central  nervous  system. 
It  seems  probable  that  under  normal  conditions — that  is,  under 
the  influence  of  what  we  may  call  minimal  stimuli — some  portions 
of  the  nerve  centers  remain  in  more  or  less  constant  activity  during 
the  day  without  showing  a  marked  degree  of  fatigue,  just  as  our 
muscles  remain  in  a  more  or  less  continuous  state  of  tonic  con- 
traction throughout  the  waking  period  at  least.  Doubtless  when 
the  stimulation  is  stronger  the  fatigue  is  more  marked,  because  the 
processes  of  repair  in  the  nerve  centers  can  not  then  keep  pace 
with  the  processes  of  consumption  of  material.  In  general,  it 
may  be  held  that  every  tissue  exhibits  a  certain  balance  between 
the  processes  of  consumption  of  material  associated  with  activity 
and  the  processes  of  repair.  If  a  proper  interval  of  rest  is  allowed, 
the  tissue  will  function  without  exhibiting  fatigue,  as  is  the  case 
with  the  heart  and  the  respiratory  center.  If,  however,  the  stimu- 
lation is  too  strong  or  is  repeated  at  too  brief  an  interval,  then  the 
processes  of  repair  do  not  keep  pace  with  those  of  consumption, 
or  the  products  of  functional  activity  are  not  completely  removed, 
and  in  either  case  we  have  the  phenomenon  of  fatigue,  that  is  to  say, 
a  depression  of  normal  irritability.  The  point  of  importance  is 
to  determine  the  differences  in  this  respect  between  the  different 
tissues.  Our  actual  knowledge  on  this  point  as  regards  nerve 
cells  is  quite  incomplete.  Evidence  of  a  probable  chemical 
change  in  the  nerve  cells  during  activity  is  found  in  the  readi- 
ness with  which  the  gray  matter  of  the  nervous  system  takes 
on  an  acid  reaction.*  In  the  fresh  resting  state  it  is  prob- 
ably alkaline  or  neutral,  but  after  death  it  quickly  shows  an 
acid  reaction,  due,  it  is  said,  to  the  production  of  lactic  acid.  Its 
resemblance  to  the  muscle  in  this  respect  leads  to  the  inference 
that  in  functional  activity  acid  is  also  produced.  Mosso  states 
that  in  the  brain  increased  mental  activity  is  accompanied  by  a 
rise  in  the  temperature  of  the  brain,  f  His  experiments  were  made 
upon  individuals  with  an  opening  in  the  skull  through  which  a 
delicate  thermometer  could  be  inserted  so  as  to  lie  in  contact  with 
brain.  So  also  the  facts  briefly  mentioned  in  regard  to  the  Nissl 
granules  give  some  corroborative  evidence  that  the  activity  of 
the  nervous  system  is  accompanied  by  and  probably  caused  by 
a  chemical  change  within  the  cells,  since  the  excessive  activity  of 
the  nerve  cells  seems  to  be  accompanied  by  some  change  in  these 
granules,  and  in  abnormal  conditions  associated  with  loss  of  func- 

*  Langendorff,  "Centralbl.  f.  d.  med.  Wiss.,"  1886.     See  also  Halliburton, 
"The  Croonian  Lectures  on  The  Chemical  Side  of  Nervous  Activity,"  1901. 
t  Mosso,  "Die  Temperatur  des  Gehirns,"  1894. 


PROPERTIES    OF    THE    NERVE    CELL. 


137 


tional  activity  the  granules  undergo  chromatolysis, — that  is,  they 
are  disintegrated  and  dissolved.  Obvious  histological  changes  which 
imply,  of  course,  a  change  in  chemical  structure,  have  been  observed 
by  a  number  of  investigators.*  All  seem  to  agree  that  activity  of 
the  tissue,  whether  normal  or  induced  by  artificial  stimulation, 
may  cause  visible  changes  in  the  appearance  of  the  cell  and  its 


Fig.  65. — Spinal  ganglion  cells  from  English  sparrows,  to  show  the  daily  variation  in 
the  appearance  of  the  cells  due  to  normal  activity:  A.  Appearance  of  cells  at  the  end  of 
an  active  day:  B,  appearance  of  cells  in  the  morning  after  a  night's  rest.  The  cytoplasm 
is  filled  with  clear,  lenticular  masses,  which  are  much  more  evident  in  the  rested  cells  than 
in  those  fatigued. — (Hodge.) 

nucleus.  Activity  within  normal  limits  may  cause  an  increase  in 
the  size  of  the  cell  together  with  a  diminution  in  the  stainable 
(Nissl)  substance,  and  excessive  activity  a  diminution  in  size  of  the 
cell  and  the  nucleus,  the  formation  of  vacuoles  in  the  cell  body, 
and  a  marked  effect  upon  the  stainable  material.  Hodge  has 
shown  that  in  birds,  for  instance,  the  spinal  ganglion  cells  of  a 
swallow  killed  at  nightfall  after  a  day  of  activity  exhibit  a  marked 
loss  of  substance  as  compared  with  similar  cells  from  an  animal 
killed  in  the  early  morning  (Fig.  65) .  Dolley  f  also  states  that  in 
the  dog  the  cerebellar  cells  exhibit  a  definite  series  of  changes  in 
the  chromatic  substance,  both  that  within  the  nucleus  and  that 
within  the  cytoplasm  (Nissl's  granules)  following  upon  prolonged 
muscular  activity  or  after  such  conditions  as  shock  or  anemia. 
If  these  conditions  are  extreme,  the  chromatin  material  may  be 
entirely  removed  from  the  cells,  and  this  he  interprets  as  an  indica- 
tion of  a  functionally  exhausted  cell. 

*  See  especially  Hodge,  "Journal  of  Morphology,"  7,  95,  1892,  and 
9,  1,  1894. 

t  Dolley,  "American  Journal  of  Physiology,"  25,  151,  1909. 


138  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

It  must  be  remembered,  however,  that  our  knowledge  of  the 
nature  of  the  chemical  changes  that  occur  in  the  cell  during  activity 
is  very  meager.  Presumably  carbon  dioxid  and  lactic  acid  are 
formed  as  in  muscle,  and  we  know  that  oxygen  is  consumed. 
Enough  is  known  perhaps  to  justify  the  general  view  that  the  energy 
exhibited  by  the  nervous  system  is  derived,  in  the  long  run,  from 
a  metabolism  of  material  'in  the  nerve  cells,  a  metabolism  which 
consists  essentially  in  the  splitting  and  oxidation  of  the  complex 
substances  hi  the  protoplasm  of  the  cell. 

Summation  of  the  Effects  of  Stimuli. — In  a  muscle  a  series 
of  stimuli  will  cause  a  greater  amount  of  shortening  than  can  be 
obtained  from  a  single  stimulus  of  the  same  strength.  In  this  case 
the  effects  of  the  stimuli  are  summated,  one  contraction  taking 
place  on  top  of  another,  or  to  put  it  in  another  way,  the  muscle 
while  in  a  condition  of  contraction  from  one  stimulus  is  made  to 
contract  still  more  by  the  following  stimulus.  In  the  nerve  fiber 
such  a  phenomenon  has  not  been  demonstrated.  In  the  nerve 
cell  it  is  usually  taught  that  the  power  of  summation  is  a  charac- 
teristic property.  It  is  pointed  out  that,  while  a  single  stimulus 
applied  to  a  sensory  nerve  may  be  ineffective  in  producing  a  reflex 
response  from  the  central  nervous  system,  a  series  of  such  stimuli 
will  call  forth  a  reaction.  In  this  case  it  is  assumed  that  the  effects 
of  the  succeeding  stimuli  are  summated  within  the  nerve  cells 
through  which  the  reflex  takes  place,  and,  generally  speaking,  it 
is  assumed  in  physiology  that  the  nerve  centers  are  adapted  by 
their  power  of  summation  to  respond  to  a  series  of  stimuli  or  to 
continuous  stimulation.  The  best  examples  of  this  kind  of  action 
are  obtained  perhaps  from  sensory  nerves,  in  which  case  we  judge 
of  the  intensity  of  the  cell  activity  by  the  concomitant  sensation, 
or  by  a  reflex  response. 

Response  of  the  Nerve  Cell  to  Varying  Rates  of  Stimula- 
tion. —The  various  parts  of  the  neuromuscular  apparatus — 
namely,  the  nerve  cell,  the  nerve  fiber,  and  the  muscle  fiber — have 
different  degrees  of  responsiveness  to  repeated  stimuli,  and  this 
responsiveness  varies,  moreover,  for  the  different  kinds  of  mus- 
cles and  of  nerve  fibers,  and,  probably  for  the  different  kinds 
of  nerve  cells.  The  motor  cells  of  the  brain  and  cord  discharge 
their  impulses  under  normal  stimulation  at  a  certain  rhythm 
which  was  formerly  supposed  to  average  about  10  per  second, 
but  is  now  estimated  as  varying  between  certain  wide  limits, 
perhaps  from  40  to  100  per  second  (p.  46).  For  any  particular 
group  of  these  motor  cells  the  evidence  indicates  that  it  has  a  prac- 
tically constant  rate  whatever  may  be  the  intensity  of  the  stimulus 
— and,  indeed,  when  artificial  stimulation  is  used  and  the  rate  is 
varied,  the  evidence  that  we  have  so  far  appears  to  show  that 


PROPERTIES    OF    THE    NERVE    CELL.  139 

the  nerve  cells  do  not  discharge  in  a  one  to  one  correspondence 
with  the  rate  of  stimulation,  as  is  the  case,  within  limits,  for 
muscle  and  nerve  fibers.  On  the  contrary,  under  such  circum- 
stances the  discharge  from  the  nerve  cells  takes  place  in  a  rhythm 
characteristic  of  the  cells  and  independent  of  that  of  the  stimula- 
tion.* From  this  point  of  view  we  must  look  upon  these  nerve 
cells  as  possessing  fundamentally  a  rhythmic  activity,  as  in  the 
case  of  the  heart.  There  is  no  doubt,  however,  that  some  at  least 
of  the  motor  cells  of  the  spinal  cord  can  be  stimulated  by  a  single 
stimulus  so  as  to  respond  witfc  a  single  discharge  instead  of  a  rhyth- 
mical series  of  discharges.  As  will  be  described  below,  the  knee- 
kick  is  a  simple  muscular  contraction,  not  a  tetanus,  which  is 
aroused  by  reflex  stimulation  of  the  corresponding  motor  cells  in 
the  spinal  cord. 

The  Refractory  Period  of  the  Nerve  Cell.— It  will  be  recalled 
that  the  nerve  fiber  exhibits  what  is  called  a  refractory  period  for  a 
brief  interval  (0.002  to  0.006  sec.)  after  it  is  stimulated.  During 
this  period  it  is  not  irritable  to  a  second  stimulus.  The  same 
phenomenon  is  exhibited  to  a  marked  degree  by  the  heart  muscle 
and  likewise  by  many  nerve  cells.  In  the  motor  nerve  cell  which 
shows  the  property  of  discharging  a  series  of  impulses  with  rhythmic 
regularity  it  may  be  supposed  that  the  refractory  period  is  marked, 
and  indeed  is  connected  probably  with  the  rhythmic  character  of 
the  cell's  activity.  But  in  this  as  in  other  properties  it  is  certain 
that  there  are  great  differences  in  the  many  varieties  of  nerve  cells 
found  in  the  central  nervous  system.  While  those  that  act  rhyth- 
mically have  probably  a  relatively  long  refractory  period,  others 
may  exhibit  a  period  of  unirritability  but  little  longer  than  that 
shown  by  the  nerve  fibers.  In  the  case  of  the  reflex  motor  centers 
in  the  lumbar  spinal  cord  of  the  frog  it  is  stated  (Langendorff)  that 
a  second  stimulus  falling  at  an  interval  of  0.04  sec.  after  the  first 
is  effective.  The  refractory  period  of  these  cells  is  less,  therefore, 
than  this  interval. 

*  Horsley  and  Schafer,  "Journal  of  Physiology,"  7,  96,  1886. 


CHAPTER  VII. 
REFLEX  ACTIONS. 

Definition  and  Historical. — By  a  reflex  action  we  mean  the 
involuntary  production  of  activity  in  some  peripheral  tissue  in 
consequence  of  a  stimulation  of  afferent  nerve  fibers.  The  conver- 
sion of  the  sensory  or  afferent  impulse  into  a  motor  or  efferent 
impulse  is  effected  in  the  nerve  centers,  and  may  be  totally  uncon- 
scious as  well  as  involuntary, — for  instance,  the  emptying  of  the 
gall-bladder  during  digestion,  or  it  may  be  accompanied  by  con- 
sciousness of  the  act,  as,  for  example,  in  the  winking  reflex  when  the 
eye  is  touched.  The  application  of  the  term  reflex  to  such  acts 
seems  to  have  been  made  first  by  Descartes*  (1649),  on  the  analogy 
of  the  reflection  of  light,  the  sensory  effect  in  these  cases  being 
reflected  back,  so  to  speak,  as  a  motor  effect.  The  attention  of  the 
early  physiologists  was  directed  to  these  involuntary  movements 
and  many  instances  were  collected,  both  in  man  and  the  lower  ani- 
mals. Their  involuntary  character  was  emphasized  by  the  dis- 
covery that  similar  movements  are  given  by  decapitated  animals, — 
frogs,  eels,  etc. 

Some  of  the  earlier  physiologists  thought  that  the  reflex  might 
occur  in  the  anastomoses  of  the  nerve  trunks,  but  a  convincing 
proof  that  the  central  nervous  system  is  the  place  of  reflection  or 
turning-point  was  given  by  Whytt  (1751).  He  showed  that  in  a  de- 
capitated frog  the  reflex  movements  are  abolished  if  the  spinal  cord 
is  destroyed.  Modern  interest  in  the  subject  was  excited  by  the 
numerous  works  of  Marshall  Hall  (1832-57),  who  contributed  a 
number  of  new  facts  with  regard  to  such  acts,  and  formulated  a 
view,  not  now  accepted,  that  these  reflexes  are  mediated  by  a  spe- 
cial set  of  fibers — the  excitomotor  fibers. 

In  describing  reflexes  the  older  physiologists  had  in  mind  only 
reflex  movements,  but  at  the  present  time  we  recognize  that  the 
reflex  act  may  affect  not  only  the  muscles, — voluntary,  involuntary, 
and  cardiac, — but  also  the  glands.  We  have  to  deal  with  reflex 
secretions  as  well  as  reflex  movements. 

The  Reflex  Arc. — It  is  implied  in  the  definition  of  a  reflex 
that  both  sensory  and  motor  paths  are  concerned  in  the  act.  Ac- 

*  See  Eckhard,  "  Geschichte  der  Entwickelung  der  Lehre  von  den  Reflex- 
erscheinungen,"  "  Beitrage  zur  Anatomie  u.  Physiologic/'  Giessen,  1881,  vol 
ix. 

140 


REFLEX    ACTIONS. 


141 


cording  to  the  neuron  theory,  therefore,  the  simplest  reflex  arc 
must  consist  of  two  neurons:  the  sensory  neuron,  whose  cell 
body  lies  in  the  sensory  ganglia  of  the  posterior  roots  or  of 
the  cranial  nerves,  and  a  motor  neuron,  whose  nerve  cell  lies 
in  the  anterior  horn  of  gray  matter  of  the  cord  or  in  the  motor 
nucleus  of  a  cranial  nerve.  The  reflex  arc  for  the  spinal  cord 
is  represented  in  Fig.  66.  The  arc  may,  however,  be  more 
complex.  The  sensory  fibers  entering  through  the  posterior 
roots  may  pass  upward  through  the  entire  length  of  the  cord 
to  end  in  the  medulla,  and  on  the  way  give  off  a  number  of 
collaterals  as  is  represented  in  Fig.  67,  or  they  may  make 
connections  with  intermediate  cells  which,  in  turn,  are  con- 
nected with  one  or  more  motor  neurons  (Fig.  68).  According 


Fig.  66. — Schema  to  show  the  connection  between  the  neuron  of  the  posterior  root  and  the 
neuron  of  the  anterior  root, — the  reflex  arc. 

to  these  schemata,  one  sensory  fiber  may  establish  reflex  connections 
with  a  number  of  different  motor  fibers,  or,  a  fact  which  must  be 
borne  in  mind  in  studying  some  of  the  well-known  reflex  activities 
of  the  cord  and  medulla  especially,  a  sensory  fiber  carrying  an 
impulse  which  eventually  reaches  the  cortex  of  the  cerebrum  and 
gives  rise  to  a  conscious  sensation  may,  by  means  of  its  collaterals, 
connect  with  motor  nuclei  in  the  cord  or  medulla  and  thus  at  the 
same  time  give  origin  to  involuntary  and  even  unconscious  re- 
flexes. Painful  stimulation  of  the  skin,  for  example,  may  give 
us  a  conscious  sensation  of  pain  and  at  the  same  time  reflexly 
stimulate  the  vasomotor  center  and  cause  a  constriction  of  the 
small  arteries.  The  fact  that  in  this  case  two  distinct  events  occur 
does  not  necessitate  the  assumption  that  the  impulses  from  the 
skin  are  carried  to  the  cord  by  two  different  varieties  of  fibers. 


142 


PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 


It  may  well  be  that  one  variety  of  sensory  neuron,  the  so-called 
pain  fibers,  effects  both  results,  because  of  the  opportunities  in 
the  cord  for  connections  with  different  groups  of  nerve  cells. 

The  Reflex  Frog. — The  motor  reflexes  from  the  spinal  cord 
can  be  studied  most  successfully  upon  a  frog  in  which  the  brain 
has  been  destroyed  or  whose  head  has  been  cut  off.  After  such 
an  operation  the  animal  may  for  a  time  suffer  from  shock,  but 
a  vigorous  animal  will  usually  recover  and  after  some  hours  will 


Fig.  67.— Kolliker's  schema  to  show 
the  direct  reflex  arc.  It  shows  the  pos- 
terior root  fiber  (black)  entering  the 
cord,  dividing  in  Yi  and  connecting  with 
motor  cells  (red)  by  means  of  collater- 
als. 


Fig.  68.  —Kolliker's  schema  to 
show  the  reflex  arc  with  intercal- 
ated tract  cells.  Posterior  root  fiber, 
black;  intercalated  tract  cell,  blue; 
motor  cells,  red. 


exhibit  reflex  movements  that  are  most  interesting.  The  funda- 
mental characteristics  of  reflex  movements  in  their  relations  to  the 
place,  intensity,  and  quality  of  the  stimulus  can  be  studied  with 
more  ease  upon  an  animal  whose  cord  is  thus  severed  from  the 
brain  than  upon  a  normal  animal.  In  the  latter  case  the  connec- 
tions in  the  nervous  system  are  more  complex  and  the  reactions 
are  therefore  less  simple  and  less  easily  kept  constant. 

Spinal  Reflex  Movements. — The  reflex  movements  obtained 
from  the  spinal  cord  or  from  other  parts  of  the  central  nervous  system 
may  be  divided  into  three  groups  by  characteristics  that  are  physio- 
logically significant.  These  classes  are:  (1)  Simple  reflexes,  or 
those  in  which  a  single  muscle  is  affected.  The  best  example  of 


REFLEX    ACTIONS.  143 

this  group  is  perhaps  the  winking  reflex,  in  which  only  the  orbic- 
ularis  palpebrarum  is  concerned.  (2)  Co-ordinated  reflexes,  in 
which  a  number  of  muscles  react  with  their  contractions  so  grad- 
uated as  to  time  and  extent  as  to  produce  an  orderly  and  useful 
movement.  (3)  Convulsive  reflexes,  such  as  are  seen  in  spasms, 
in  which  a  number  of  muscles — perhaps  all  the  muscles — are  con- 
tracted convulsively,  without  co-ordination  and  with  the  pro- 
duction of  disorderly  and  useless  movements.  Of  these  groups, 
the  co-ordinated  reflexes  are  by  far  the  most  interesting.  They 
can  be  obtained  to  perfection  from  the  reflex  frog.  In  such  an 
animal  no  spontaneous  movements  occur  if  the  sensory  surfaces  are 
entirely  protected  from  stimulation.  A  sudden  stimulus,  however, 
of  sufficient  strength  applied  to  any  part  of  the  skin  will  give  a 
definite  and  practically  invariable  response  in  a  movement  which 
has  the  appearance  of  an  intentional  effort  to  escape  from  or  remove 
the  stimulus.  If  the  toe  is  pinched  the  foot  is  withdrawn — in  a 
gentle  manner  if  the  stimulus  is  light,  more  rapidly  and  violently, 
but  still  in  a  co-ordinated  fashion,  if  the  stimulus  is  strong.  If 
the  animal  is  suspended  and  various  spots  on  its  skin  are  stimulated 
by  the  application  of  bits  of  paper  moistened  with  dilute  acetic 
acid  the  animal  will  make  a  neat  and  skillful  movement  of  the 
corresponding  leg  to  remove  the  stimulating  body.  The  reactions 
may  be  varied  in  a  number  of  ways,  and  in  all  cases  the  striking 
features  of  the  reflex  response  are,  first,  the  seemingly  purposeful 
character  of  the  movement,  and,  second,  the  almost  mechanical 
exactness  with  which  a  definite  stimulus  will  give  a  definite  response. 
This  definite  relationship  holds  only  for  sensory  stimulation  of  the 
external  integument,  the  skin  and  its  organs.  It  is  obvious,  in 
fact,  that  a  muscular  response  can  be  effective  only  for  stimuli 
originating  from  the  external  surface.  Stimuli  from  the  interior 
of  the^  body  exert  their  reactions,  for  the  most  part,  upon  the  plain 
musculature  and  the  glands.  The  convulsive  reflexes  may  be 
produced  by  two  different  means  :  (1)  By  very  intense  sensory 
stimulation.  The  reflex  response  in  this  case  overflows,  as  it  were, 
into  all  the  motor  paths.  A  variation  of  this  method  is  seen  in  the 
well-known  convulsive  reaction  that  follows  tickling.  In  this  case 
the  stimulus,  although  not  intense  from  an  objective  standpoint, 
is  obviously  violent  from  the  standpoint  of  its  effectiveness  in 
sending  into  the  central  nervous  system  a  series  of  maximal  sensory 
impulses.  (2)  By  heightening  the  irritability  of  the  central  nervous 
system.  Upon  the  reflex  frog  this  effect  is  obtained  most  readily 
by  the  use  of  strychnin.  A  little  strychnin  injected  under  the 
skin  is  soon  absorbed  and  its  effect  is  shown  at  first  by  a  greater 
sensitiveness  to  cutaneous  stimulation,  the  slightest  touch  to 
the  foot  causing  its  withdrawal.  Soon,  however,  the  response, 
instead  of  being  orderly  and  adapted  to  a  useful  end,  becomes 


144  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

convulsive.  A  mere  touch  of  the  skin  or  a  current  of  air  will  throw 
every  muscle  into  contraction,  and  the  extensors  being  stronger  than 
the  flexors  the  animal's  body  becomes  rigid  in  extension  at  every 
stimulation.  The  explanation  usually  given  for  this  result  is  that 
the  strychnin,  acting  upon  some  part  of  the  nerve  cells,  increases 
greatly  their  irritability,  so  that  when  a  stimulus  is  sent  into  the 
central  nervous  system  .along  any  sensory  path  from  the  skin  it 
apparently  radiates  throughout  the  cord  and  acts  upon  all  the 
motor  cells.  This  latter  supposition  leads  to  the  interesting  con- 
clusion that  all  the  various  motor  neurons  of  the  cord  must  be  in 
physiological  connection,  either  direct  or  indirect,  with  all  the 
neurons  supplying  the  cutaneous  surface.  The  further  fact  that 
under  normal  conditions  the  effect  of  a  given  sensory  stimulus  is 
manifested  only  on  a  limited  and  practically  constant  number 
of  the  motor  neurons  seems  to  imply,  therefore,  that  normally  the 
paths  to  these  neurons  are  more  direct  and  the  resistance,  if  we 
may  use  a  somewhat  figurative  term,  is  less  than  that  offered  by 
other  possible  paths.  Muscular  spasms  are  observed  under  a  number 
of  pathological  conditions, — for  instance,  in  hydrophobia.  We  are 
at  liberty  to  assume  in  such  cases  that  the  toxins  produced  by  the 
disease  affect  the  irritability  of  the  cells  in  much  the  same  way  as 
the  strychnin. 

Theory  of  Co-ordinated  Reflexes. — The  purposeful  character 
of  the  co-ordinated  reflexes  in  the  frog  gives  the  impression  to  the 
observer  of  a  conscious  choice  of  movements  on  the  part  of  the 
brainless  animal.  Most  physiologists,  however,  are  content  to  see 
in  these  reactions  only  an  expression  of  the  automatic  activity 
of  a  mechanism.  It  is  assumed  that  the  sensory  impulses  from 
any  part  of  the  skin  find,  on  reaching  the  cord,  that  the  paths  to 
a  certain  group  of  motor  neurons  are  more  direct  and  offer  less 
resistance  than  any  others.  It  is  along  these  paths  that  the  reflex 
will  take  place,  and  we  may  further  assume  that  these  paths  of 
least  resistance,  as  they  have  been  called,  are  in  part  preformed 
and  in  part  are  laid  down  by  the  repeated  experiences  of  the  indi- 
vidual. That  is,  in  each  animal  a  definite  structure  may  be  sup- 
posed to  exist  in  the  cord;  each  sensory  neuron  is  connected  with 
a  group  of  motor  neurons,  to  some  of  them  more  directly  than  to 
others,  and  we  may  imagine,  therefore,  a  system  of  reflex  apparatuses 
or  mechanisms  which  when  properly  stimulated  will  react  always 
in  the  same  way.  And,  indeed,  in  spite  of  the  adapted  character 
of  the  reflexes  under  consideration  their  automaton-like  regularity 
is  an  indication  that  their  production  is  due  to  a  fixed  mechanical 
arrangement.  Whether  the  reactions  of  the  nervous  system  in 
such  cases  are  accompanied  by  any  degree  of  consciousness  can 
not  be  proved  or  disproved,  but  the  assumption  of  such  an  accom- 
paniment does  not  seem  necessary  to  explain  the  reaction. 


REFLEX   ACTIONS.  145 

Spinal  Reflexes  in  the  Mammals. — Experiments  upon  the  lower 
mammals  show  that  co-ordinated  reflex  movements  may  be  ob- 
tained from  the  cord  after  severance  of  its  connections  with  the 
brain.  Sherrington*  has  described  a  simple  operation  by  which  the 
head  may  be  removed  from  an  anesthetized  cat  and  the  animal  be 
kept  alive  for  a  number  of  hours.  Stimulation  of  the  skin  in  such 
an  animal  calls  forth  numerous  definite  reflexes,  such  as  flexion  or 
extension  of  the  legs,  the  scratching  movements  of  the  hind  legs, 
stretching  movements,  etc.  Or  the  spinal  cord  may  be  severed  in 
the  thoracic  region,  below  the  origin  of  the  phrenic  nerves,  and  the 
animal,  with  care,  can  be  kepjb  alive  for  months  or  years.  In  such 
an  animal  reflex  movements  of  the  hind  legs  or  tail  may  be  ob- 
tained readily  from  slight  sensory  stimulation  of  the  skin.  The 
knee-jerk  and  similar  so-called  deep  reflexes  are  also  retained.  But 
it  is  evident  that  these  movements  are  not  so  complete  nor  so 
distinctly  adapted  to  a  useful  end  as  in  the  frog.  The  muscles  of 
the  body  supplied  by  the  isolated  part  of  the  cord  retain,  however, 
a  normal  irritability  and  exhibit  no  wasting.  In  man,  on  the 
contrary,  it  is  stated  that  after  complete  section  of  the  cord  the  deep 
reflexes,  such  as  the  knee-jerk,  as  well  as  the  skin  reflexes,  are  very 
quickly  lost.  The  muscles  undergo  wasting  and  soon  lose  their 
irritability.!  The  monkeys  exhibit  in  this  respect  a  condition  that 
is  somewhat  intermediate  between  that  of  the  dog  and  man.  It 
seems  evident  from  these  facts  that  in  the  lower  animals,  like  the 
frog,  a  much  greater  degree  of  independent  activity  is  exhibited  by 
the  cord  than  in  the  more  highly  developed  animals.  According  to 
the  degree  of  development,  the  control  of  the  muscles  is  assumed 
more  and  more  by  the  higher  portions  of  the  nervous  system,  and 
the  spinal  cord  becomes  less  important  as  a  series  of  reflex  centers, 
its  functions  being  more  dependent  upon  its  connections  with  the 
higher  centers. 

Dependence  of  Co-ordinated  Reflexes  upon  the  Excitation 
of  the  Normal  Sensory  Endings, — It  is  an  interesting  fact  that 
when  a  nerve  trunk  is  stimulated  directly  in  a  reflex  frog — the 
sciatic  nerve,  for  instance — the  reflex  movements  are  disorderly 
and  quite  unlike  those  obtained  by  stimulating  the  skin.  It  is  said 
that  if  the  skin  be  loosened  and  the  nerve  twigs  arising  from  it  be 
stimulated,  an  operation  that  is  quite  possible  in  the  frog,  the  re- 
sponse is  again  a  disorderly  reflex,  whereas  the  same  fibers  stimu- 
lated through  the  skin  give  an  orderly,  co-ordinated  movement. 
The  difference  in  response  in  these  cases  is  probably  not  due  to  any 
peculiarity  in  the  nature  of  the  sensory  impulses  originating  in  the 
nerve  endings  of  the  skin,  but  more  likely  to  a  difference  in  their 
strength  and  arrangement.  When  one  stimulates  a  sensory  nerve 
*  Sherrington,  "Journal  of  Physiology,"  38,  375,  1909. 
t  See  Collier,  "  Brain,"  1904,  p.  38. 
10 


146  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

trunk  directly, — the  ulnar  nerve  at  the  elbow  in  ourselves,  for  in- 
stance,— the  resulting  sensations  are  markedly  different  from  those 
obtained  by  stimulating  the  skin  areas  supplied  by  the  same  nerve ; 
we  have  little  or  no  sensations  of  touch  or  temperature,  only  pain 
and  a  peculiar  tingling  in  the  fingers.  In  such  an  experiment  the 
stimulus  applied  to  the  trunk  affects  more  or  less  equally  all  the 
contained  fibers,  whereas  in  stimulation  of  the  skin  itself  the  effect 
upon  the  cutaneous  fibers  of  pressure,  temperature,  or  pain  pre- 
dominates and  presumably  it  is  these  fibers  that  normally  are  con- 
nected in  an  efficient  way  with  the  reflex  machinery  in  the  nerve 
centers. 

Reflex  Time. — Since  nerve  centers  are  involved  in  a  reflex 
movement,  a  determination  of  the  total  time  between  the  appli- 
cation of  the  stimulus  and  the  beginning  of  the  response  gives 
a  means  of  ascertaining  the  time  needed  for  the  processes  within 
the  nerve  cells.  Helmholtz,  who  first  made  experiments  of  this 
kind,  stated  that  the  time  required  within  the  nerve  centers 
might  be  as  much  as  twelve  times  as  great  as  that  estimated 
for  the  conduction  along  the  motor  and  sensory  nerves 
involved  in  the  reflex.  Most  observers  state  that  the  time 
within  the  center  varies  with  the  strength  of  the  stimulus, 
being  less,  the  stronger  the  stimulus.  It  varies  also  with  the 
condition  of  the  nerve  centers,  being  lengthened  by  fatigue 
and  other  conditions  that  depress  the  irritability  of  the  nerve 
cells.  By  reflex  time  or  reduced  reflex  time  we  may  designate 
the  time  required  for  the  processes  in  the  center, — that  is,  the  total 
time  less  that  required  for  transmission  of  the  impulse  along  the 
motor  and  sensory  fibers  and  the  latent  period  of  the  muscle  con- 
traction. For  the  frog  this  is  estimated  as  varying  between 
0.008  and  0.015  sec.  In  man  the  reflex  time  usually  quoted  is  that 
given  by  Exner  for  the  winking  of  the  eye.  He  stimulated  one  lid 
electrically  and  recorded  the  reflex  movement  of  the  lid  of  the  other 
eye.  The  total  time  for  the  reflex  was,  on  an  average,  from  0.0578 
sec.  to  0.0662  sec.  He  estimated  that  the  time  for  transmission  of 
the  impulse  along  the  sensory  and  motor  paths,  together  with  the 
latent  period  of  the  muscle,  amounted  to  0.0107  sec.  So  that  the 
true  reflex  time  from  his  determinations  varied  between  0.0471  and 
0.0555  sec.  Mayhew,*  using  a  more  elaborate  method,  obtained 
for  the  total  time  a  mean  figure  equal  to  0.0420  sec.  If  Exner 's 
correction  is  applied  then  the  true  reflex  time  according  to  this  de- 
termination is  equal  to  0.0313  sec.  In  a  series  of  experiments 
made  upon  frogs,  in  which  the  efferent  response  to  stimulation 
of  the  afferent  fibers  of  the  sciatic  nerve  was  measured  by  the 
electrical  variation  in  the  muscle  involved,  Buchanan  finds  that 
the  delay  in  the  cord,  when  the  reflex  was  on  the  same  side,  was 
*  Mayhew,  "Journal  of  Exp.  Medicine,"  2,  35,  1897. 


REFLEX    ACTIONS.  147 

equal  to  0.01  to  0.02  sec.  If  the  reflex  was  on  the  crossed  side 
about  double  this  time  was  consumed  in  the  cord.  This  delay 
of  the  velocity  of  transmission  of  an  impulse  in  the  nerve  centers 
is  a  factor  which  must  vary  somewhat  in  different  parts  of  the 
nervous  system.  It  has  been  shown  that,  in  certain  cases  at 
least,  when  strong  stimuli  are  used  the  latent  period  of  a  reflex 
is  not  greater  than  would  be  accounted  for  by  transmission 
through  the  nerve  fibers  and  by  the  latency  of  the  muscular 
contraction.  Thus  Franyois  Frank,  in  an  experiment  in  which 
the  gastrocnemius  muscle  of  one  side  was  made  to  contract 
reflexly  by  stimulation  of  the  afferent  root  of  a  lumbar  nerve 
on  the  other  side,  records  a  latent  period  of  only  0.017  sec. 
Evidently  in  such  a  case  there  was  no  perceptible  delay  in 
passing  through  the  nerve  centers  of  the  lumbar  cord. 

Inhibition  of  Reflexes. — One  of  the  most  fundamental  facts 
regarding  spinal  reflexes  is  the  demonstration  that  they  can  be 
depressed  or  suppressed  entirely — that  is,  inhibited — by  other  im- 
pulses reaching  the  same  part  of  the  spinal  cord.  The  most  sig- 
nificant experiment  in  this  connection  is  that  made  by  Setschenow.* 
If  in  a  frog  the  entire  brain  or  the  cerebral  hemispheres  are  re- 
moved, then  stimulation  of  the  exposed  cut  surface — for  instance, 
by  crystals  of  sodium  chlorid — will  depress  greatly  or  perhaps 
inhibit  entirely  the  usual  spinal  reflexes  that  may  be  obtained  by 
cutaneous  stimulation.  On  removal  of  the  stimulating  substance 
from  the  cut  surface  by  washing  with  a  stream  of  physiological 
saline  (solution  of  sodium  chlorid,  0.7  per  cent.)  the  reflex  activities 
of  the  cord  are  again  exhibited  in  a  normal  way.  This  experiment 
accords  with  many  facts  which  indicate  that  the  brain  may  inhibit 
the  activities  of  the  spinal  centers.  In  the  reflex  from  tickling, 
for  instance,  we  know  that  by  a  voluntary  act  we  can  repress  the 
muscular  movements  up  to  a  certain  point;  so  also  the  limited 
control  of  the  action  of  the  centers  of  respiration  and  micturition 
is  a  phenomenon  of  the  same  character.  To  explain  such  acts  we 
may  assume  the  existence  of  a  definite  set  of  inhibitory  fibers, 
arising  in  parts  of  the  brain  and  distributed  to  the  spinal  cord, 
whose  function  is  that  of  controlling  the  activities  of  the  spinal 
centers.  In  view  of  the  fact,  however,  that  there  is  no  independent 
proof  of  the  existence  of  a  separate  set  of  inhibitory  fibers  within 
the  central  nervous  system — that  is,  a  set  of  fibers  whose  specific 
energy  is  that  of  inhibition — it  is  preferable  to  speak  simply  of 
the  inhibitory  influence  of  the  brain  upon  the  cord,  leaving  unde- 
cided the  question  as  to  whether  this  influence  is  exerted  through 
a  special  set  of  fibers,  or  is  brought  about  by  some  variation  in 

*  Setschenow,  "  Physiologische  Studien  iiber  d.  Hemmungs-Mechanismen 
f.  d.  Reflexthatigkeit  im  Gehirn  d.  Frosches,"  Berlin,  1863. 


148  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

the  time  relations,  intensity,  or  quality  of  the  nerve  impulses. 
Regarding  the  fact,  however,  there  can  be  no  question,  and  it 
constitutes  a  most  important  factor  in  the  interaction  of  the  dif- 
ferent parts  of  the  nervous  system.  It  is  probable  that  this  factor 
explains  why  a  normal  frog  gives  reflexes  that  are  so  much  less 
constant  and  less  predictable  than  one  with  its  brain  removed. 
A  similar  inhibition  of  spinal  reflexes  may  be  obtained  by  simul- 
taneous stimulation  of  two  different  parts  of  the  skin.  The 
usual  reflex  from  pinching  the  toe  of  one  leg  may  be  inhibited  in 
part  or  completely  by  simultaneous  stimulation  of  the  other  leg 
or  by  direct  electrical  stimulation  of  an  exposed  nerve  trunk.  A 
similar  interference  is  illustrated,  perhaps,  in  the  well-known 
device  of  inhibiting  an  act  of  sneezing  by  a  strong  sensory 
stimulation  from  some  part  of  the  skin — for  instance,  by  pressing 
upon  the  upper  lip.  The  importance  of  the  process  of  inhibition 
in  the  normal  movements  of  the  body  is  illustrated  strikingly 
by  the  phenomenon  known  as  reciprocal  innervation,  which  has 
been  investigated  chiefly  by  Sherrington.*  This  observer  has 
found  that  when  a  flexor  muscle  is  stimulated  reflexly  there  is 
at  the  same  time  a  relaxation  or  loss  of  tone  in  its  antagonistic 
extensor,  which  is  explained  as  being  due  to  an  inhibition  of  the 
motor  cells  of  the  extensor  in  the  cord.  Reflex  stimulation  of 
the  extensor  is  accompanied  similarly  by  an  inhibition  of  the 
tone  of  the  antagonistic  flexor.  This  phenomenon  has  been 
demonstrated  not  only  for  reflex  stimulation  of  the  cord  but 
also  for  voluntary  movements  (Athanasieu)  and  for  electrical 
stimulation  of  the  cortical  centers.  The  motor  centers  of  the 
muscles  surrounding  the  joints  are  apparently  so  connected  in 
pairs  that  when  one  is  excited  the  center  of  the  corresponding 
antagonist  is  inhibited.  This  reciprocating  mechanism  dis- 
appears under  conditions,  such  as  strychnine-poisoning,  in  which,, 
according  to  the  usual  belief,  the  irritability  of  the  centers  is 
greatly  increased.  A  relationship  quite  comparable  to  the 
reciprocal  innervation,  although  working  in  only  one  direction, 
is  exhibited  by  the  peripheral  nerve  plexuses  in  the  intestinal 
canal  in  the  so-called  law  of  the  intestines  (see  p.  732).  A 
brief  statement  of  the  more  or  less  unsatisfactory  theories  of 
inhibition  is  given  in  connection  with  the  inhibitory  action  of  the 
vagus  nerve  on  the  heart  beat  (see  p.  593).  It  should  be  added, 
however,  in  this  connection,  that  stimulation  of  the  cord,  and 
probably  of  other  parts  of  the  nervous  system,  from  two  different 
sources  may  result  not  only  in  an  inhibition  of  the  reflex  normally 
occurring  from  one  of  the  stimuli,  but  under  some  circumstances 

*  Sherrington,  "The  Integrative  Action  of  the  Nervous  System,"  1906, 
p.  84. 


REFLEX    ACTIONS.  149 

may  give  an  augmentation  or  reinforcement  of  the  reflex.  A 
striking  example  of  this  augmenting  effect  is  given  below  in  the 
paragraph  upon  the  knee-kick. 

Influence  of  the  Condition  of  the  Cord  on  its  Reflex  Ac- 
tivities.— The  time  and  extent  of  the  reflex  responses  may  be 
altered  greatly  by  various  influences,  particularly  by  the  action 
of  drugs.  The  effect  in  such  cases  is  usually  upon  the  nerve  centers, 
— that  is,  upon  the  cells  themselves  or  upon  the  synapses,  that  is  to 
say,  the  connections  between  the  terminal  arborization  and  the 
dendrites — the  process  of  conduction  within  the  sensory  and 
motor  fibers  being  less  easily  affected.  A  convenient  method 
of  studying  such  influences ,.  is  that  employed  by  Tiirck.  In 
this  method  the  reflex  frog  is  suspended,  and  the  tip  of  the 
longest  toe  is  immersed  to  a  definite  point  in  a  solution  of  sul- 
phuric acid  of  a  strength  of  0.1  to  0.2  per  cent.  If  the  time 
between  the  immersion  and  the  reflex  withdrawal  of  the  foot  is 
noted  by  a  metronome,  or  by  a  record  upon  a  kymograph,  it  will 
be  found  to  be  quite  constant,  provided  the  conditions  are  kept 
uniform.  If  the  average  time  for  this  reflex  is  obtained  from  a 
series  of  observations  it  is  possible  to  inject  various  substances — 
such  as  strychnin,  chloroform,  potassium  bromid,  quinin,  etc. — 
under  the  skin,  and  after  absorption  has  taken  place  to  determine 
the  effect  by  a  new  series  of  observations.  So  far  as  drugs  are 
concerned  the  results  of  such  experiments  belong  rather  to  pharma- 
cology than  to  physiology.  The  method  in  some  cases  brings  out  an 
interesting  difference  in  the  effects  of  various  kinds  of  stimulation. 
Strychnin,  for  instance,  as  was  stated  above,  increases  greatly  the 
delicacy  of  the  reaction  to  pressure  stimulation.  At  one  stage  in 
its  action  before  the  convulsive  responses  are  obtained  the  threshold 
stimulus  is  greatly  lowered, — mere  contact  with  the  toes  causes  a 
rapid  retraction  of  the  leg;  whereas  in  the  normal  reflex  frog  a 
relatively  large  pressure  is  necessary  to  obtain  a  similar  response. 
At  this  stage  in  the  action  of  the  strychnin  the  effect  of  the  acid 
stimulus,  on  the  contrary,  may  be  markedly  weakened  so  far  as 
the  time  element  is  concerned.  If  the  action  of  the  strychnin  is 
not  too  rapid,  it  is  usually  possible  to  find  a  point  at  which  the 
time  for  the  reflex  is  diminished,  but  this  effect  quickly  disappears 
and  the  period  between  stimulus  and  response  becomes  markedly 
lengthened  at  a  time  when  the  slightest  mechanical  stimulation  gives 
a  rapid  reflex  movement.  This  paradoxical  result  may  depend  pos- 
sibly upon  the  variety  of  nerve  fiber  stimulated  by  the  two  kinds 
of  stimuli  or  may  be  connected  with  the  fact  that  the  acid 
stimuli  may  bring  about  inhibitory  as  well  as  excitatory  processes 
in  the  cord. 

Reflexes  from  Other  Parts  of  the  Nervous  System. — Nu- 
merous typical  reflexes  are  known  to  occur  in  the  brain.  The 


150  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

reflex  effects  upon  the  important  centers  in  the  medulla,  such 
as  the  vasomotor  center,  the  respiratory  center,  and  the  cardio- 
inhibitory  center,  the  winking  of  the  eye,  sneezing,  the  light  reflex 
upon  the  sphincter  muscle  of  the  iris,  and  many  other  similar  cases 
might  be  enumerated.  All  of  these  reactions  will  be  described 
and  discussed  in  their  proper  places.  The  conscious  reactions  of 
the  brain  are  not  included  among  the  reflexes  by  virtue  of  the  defi- 
nition which  lays  stress  upon  the  involuntary  characteristic  of  the 
reflex  response,  but  it  should  be  remembered  that,  so  far  as  the 
nervous  mechanism  is  concerned,  these  conscious  reactions  do  not 
differ  from  the  true  reflexes.  When  we  voluntarily  move  a  limb 
the  movement  is  guided  and  controlled  by  sensory  impulses  from  the 
muscles  put  into  action.  The  fibers  of  muscle  sense  from  these 
muscles  convey  sensory  impulses  through  a  chain  of  neurons  to 
the  cortex  of  the  brain  and  there  the  impulses  doubtless  affect  and 
set  into  action  the  motor  neurons  through  which  the  movement  is 
effected.  So  far  as  we  know,  the  discharges  from  the  efferent 
neurons  of  the  brain  do  not  arise  independently  within  these  cells, 
they  are  conditioned  or  originated  by  stimuli  from  other  neurons; 
so  that  the  activities  of  the  brain  are  carried  on  by  a  mechanism  of 
one  neuron  acting  on  another,  just  as  in  the  case  of  the  reflex  arc. 
The  added  feature  of  a  psychical  factor,  a  reaction  in  consciousness, 
enables  us  to  draw  a  line  of  distinction  between  these  activities  and 
those  of  so-called  pure  reflexes;  but  the  distinction  is  perhaps  one  of 
convenience  only,  for,  although  the  extremes  may  be  far  enough 
apart  to  suit  the  definition,  many  intermediate  instances  may  be 
found  which  are  difficult  to  classify.  All  skilled  movements,  for  in- 
stance, such  as  walking,  singing,  dancing,  bicycle  riding,  and  the 
like, — although  in  the  beginning  obviously  effected  by  voluntary 
co-ordination,  nevertheless  in  the  end,  in  proportion  to  the  skill  ob- 
tained, become  more  or  less  entirely  reflex, — that  is,  involuntary. 
In  learning  such  movements  one  must,  as  the  saying  goes,  establish 
his  reflexes,  and  the  result  can  hardly  be  understood  otherwise  than 
by  supposing  that  the  continual  adjustment  of  certain  sensory  im- 
pulses to  certain  co-ordinated  movements  results  in  the  formation 
of  a  more  or  less  complex  reflex  arc,  a  set  of  paths  of  least  resistance. 
Reflexes  through  Peripheral  Ganglia — Axon  Reflexes. — 
Many  attempts  have  been  made  by  physiologists  to  ascertain 
whether  or  not  reflexes  can  occur  through  the  peripheral  nerve 
ganglia,  lying  outside  the  central  nervous  system.  With  regard 
to  the  posterior  root  ganglia,  it  has  usually  been  supposed  that 
they  cannot  exhibit  reflexes.  When  the  posterior  root  con- 
necting such  a  ganglion  to  the  cord  is  severed,  then,  according 
to  our  usual  conception,  the  cells  in  the  ganglia  are  cut  off 
from  all  connections  with  the  peripheral  tissues  by  efferent 


REFLEX    ACTIONS. 


151 


paths.  This  usual  view  may  not,  however,  be  correct.  On 
the  physiological  side  we  have  the  fact  (see  p.  82)  that  stimu- 
lation of  certain  of  the  posterior  root  ganglia  under  such  cir- 
cumstances does  give  peripheral  effects 
on  the  blood-vessels,  causing  a  vascular  ^ 
dilatation  in  a  certain  region.  On  the 
histological  side  Cajal*  and  others  have 
shown  that  some  of  these  cells  are  provided 
with  a  pericellular  nerve  network,  which 
is  an  afferent  path  so  far  as  the  cell  is  con- 
cerned, while  the  axon  of  the  cell  con- 
stitutes an  efferent  path.  '"Whether  these 
cells  form  a  special  group  of  efferent  cells 
lying  within  the  sensory  ganglion,  or 
whether  they  are  sensory  cells  discharging 
into  the  cord  and  stimulated  reflexly 
through  the  nerve  network  as  well  as 
through  the  peripheral  process  of  the  axon, 
cannot  be  said.  The  subject  is  one  full 
of  interest  to  physiology.  In  the  ganglia 
of  the  sympathetic  nerve  and  its  appen- 
dages and  in  the  similar  ganglia  contained 
in  many  of  the  organs  the  nerve  cells  have 
dendritic  processes,  and,  so  far  as  their 
histology  is  concerned,  it  would  seem  possi- 
ble that  in  any  ganglion  of  this  type  there 
might  be  sensory  and  motor  neurons  so 
connected  as  to  make  the  ganglion  an 
independent  reflex  center.  Numerous 
experiments  have  been  made  to  determine  experimentally 
whether  reflexes  can  be  obtained  through  such  ganglia.  Perhaps 
the  most  successful  of  these  experiments  have  been  made  upon 
the  inferior  mesenteric  ganglion. 

This  ganglion  may  be  isolated  from  all  connections  with 
the  central  nervous  system  and  left  attached  to  the  bladder 
through  the  two  hypogastric  nerves  (see  Fig.  287).  If  now  one 
of  these  nerves  is  cut  and  the  central  stump  is  stimulated,  a 
contraction  of  the  bladder  follows.  Obviously  in  this  case  the 
impulse  has  traveled  to  the  ganglion  and  down  the  other  hy- 
pogastric nerve;  the  reaction  has  every  appearance  of  being  a 
true  reflex.  Nevertheless,  Langley  and  Anderson, f  who  have 
studied  the  matter  with  especial  care,  are  convinced  that  in  this 

*  Cajal,  "Ergebnisse  der  Anat.  u.  Entwickelungsgeschichte,"  vol.  xvi., 
1906;  Dogiel,  "Bail  der  Spinalganglien,  etc.,"  1908. 

f  Langley  and  Anderson,  "Journal  of  Physiology,"  16,  410,  1894. 


Fig.  69.— Schema  to 
show  idea  of  an  axon  re- 
flex: The  preganglionic 
fiber,  a,  sends  branchea 
to  two  post  ganglion  ic 
fibers,  b,  c.  If  stimulated 
at  x  the  impulse  passes 
backward  in  a  direction 
the  reverse  of  normal  and 
falling  into  6  and  c  gives 
a  pseudoreflex  effect. 


152 


PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 


and  similar  cases  we  have  to  do  with  what  they  call  pseudo- 
reflexes  or  axon  reflexes.  The  idea  underlying  this  term  may 
be  explained  in  this  way:  Every  sympathetic  ganglion  is 
connected  with  the  central  nervous  system,  brain  and  cord, 
by  efferent  spinal  fibers,  preganglionic  fibers,  which  terminate  by 
arborization  around  the  dendrites  of  the  sympathetic  cells.  The 
efferent  fibers  arising  from  the  latter  may  be  designated  as  post- 
ganglionic  fibers.  These  authors  give  reasons  to  believe  that  any 
one  preganglionic  fiber,  a,  Fig.  69,  may  connect  by  collaterals  with 
several  sympathetic  cells.  If  such  a  fiber  were  stimulated  at  x, 
then  the  impulse  passing  back  along  the  axon  in  a  direction  the 
reverse  of  normal  would  stimulate  cells  b  and  c,  giving  effects  that 
are  apparently  reflex,  but  which  differ  from  true  reflexes  in  that 
the  stimulating  axon  belongs  to  a  motor  neuron.  Under  normal 
circumstances  it  is  not  probable  that  an  effect  of  this  kind  can  be 
produced,  but  there  are  some  interesting  observations  on  record 


SKin 


Fig.  69a.-^-Schemata  of  axon-reflex  producing  local  vascular  dilatation  from  the  applica- 
tion of  an  irritant — A,  Bardy's  schema:  n,  the  sensory  fiber;  c,  the  conjunctiva;  d,  the  per- 
ipheral sympathetic  ganglion;  /,  the  blood-vessel.  The  reflex  runs  from  c  over  a  b  and  a  to 
/;  «,  a  vaso-constrictor  fiber.  B,  Bruce's  schema  (modified) :  The  arrows  indicate  the  course 
of  the  axon-reflex. 

which  indicate  that  axon-reflexes  may  play  an  important  r61e  in  the 
control  of  the  blood-supply  to  certain  areas.  When  a  membrane 
or  the  skin  is  inflamed  by  an  irritant,  it  becomes  congested  and  pain- 
ful, exhibiting,  in  fact,  the  four  classical  symptoms,  rubor,  turgor, 
oalor,  and  dolor.  Two  observers*  have  found  that  the  local  vaso- 
dilatation  caused  by  such  an  irritant  as  mustard  oil  applied  to  the 
conjunctiva  is  greatly  diminished  if  the  sensory  nerve-fibers  of  the 
region  are  paralyzed  by  a  local  anesthetic  or  if  the  same  fibers  are 
destroyed  by  degeneration  after  section.  In  other  words,  the  effect 
of  the  irritant  in  causing. local  dilatation  of  the  blood-vessels  is  not 
due  to  its  direct  action  on  the  walls  of  the  blood-vessels,  but  is  of 
the  nature  of  a  reflex  effect  through  the  nerve  supply.  Further 
experiments  indicate  that  the  effect  is  not  due  to  a  reflex  of  the 

*  Ninian  Bruce,  "Quarterly  Journal  of  Exp.  Physiol.,"  6,  339,  1913;  Bardy, 
"Skandinavisches  Archiv.  f.  Physiol.,"  32,  198,  1914. 


REFLEX    ACTIONS.  153 

ordinary  kind  through  the  central  nervous  system  or  the  posterior 
root  ganglion  or  the  superior  cervical  ganglion,  and  it  is  probably, 
therefore,  a  peripheral  reflex  of  the  nature  of  an  axon-reflex  taking 
place  wholly  through  the  sensory  nerve-fibers  or  through  such 
fibers  in  connection  with  the  small  peripheral  sympathetic  ganglia 
distributed  along  the  course  of  the  blood-vessels.  The  apparatus 
that  may  be  involved  is  represented  in  the  two  accompanying 
schemata  (Fig.  69a). 

The  Tonic  Activity  of  the  Spinal  Cord. — In  addition  to  the 
definite  reflex  activities  of  the  cord,  each  traceable  to  a  distinct 
sensory  stimulus,  there  is  evidence  to  show  that  many  of  its  motor 
neurons  are  in  that  state  of  more  or  less  continuous  activity  which 
we  designate  as  tonic  activity  or  tonus.  There  is  abundant  reason 
for  this  belief  in  regard  to  many  of  the  special  centers  of  the  cord 
and  brain,  such  as  the  vasomotor  center,  the  center  for  the  sphinc- 
ter muscle  of  the  iris,  the  centers  for  the  sphincter  muscles  of  the 
bladder,  the  anus,  etc.  But  the  evidence  includes  the  motor 
neurons  to  the  voluntary  as  well  as  the  involuntary  musculature. 
In  a  decapitated  frog  the  muscles  take  a  definite  position,  and 
Brondgeest  showed  that  if  such  an  animal  is  suspended,  after  cut- 
ting the  sciatic  plexus  in  one  leg,  the  leg  on  the  uninjured  side 
takes  a  more  flexed  position.  The  explanation  offered  for  this 
result  is  that  the  muscles  on  the  sound  side  are  being  innervated 
by  the  motor  neurons  of  the  cord.  Inasmuch  as  a  result  of  this 
kind  cannot  be  obtained  from  a  frog  whose  skin  has  been  removed, 
or  in  one  in  which  the  posterior  roots  have  been  severed  it  seems 
evident  that  this  tonic  discharge  from  the  motor  neurons  is  due 
to  a  constant  inflow  of  impulses  along  the  sensory  paths.  The 
muscle  tonus,  in  other  words,  is  really  a  reflex  tonus,  which  differs 
from  ordinary  reflex  movements  only  in  the  absence  of  a  sudden, 
visible  contraction  and  in  the  more  or  less  continuous  character 
of  the  innervation.  In  the  section  on  animal  heat  the  importance 
of  this  constant  innervation  of  the  muscles  as  a  source  of  heat  is 
further  emphasized.  The  idea  of  a  more  or  less  continuous  but 
varying  activity  of  the  centers  in  the  brain  and  cord  in  consequence 
of  the  continuous  inflow  of  impulses  along  the  sensory  paths  fits 
in  very  well  with  many  facts  observed  in  the  peripheral  organs,— 
facts  that  will  be  referred  to  from  time  to  time  as  the  physiology 
of  these  organs  is  considered. 

Effects  of  Removal  of  the  Spinal  Cord. — Numerous  investi- 
gators have  sectioned  the  cord  partly  or  completely  at  various 
levels.  The  general  results  of  these  experiments  as  regards  loss 
of  sensation  or  voluntary  movement  are  described  in  the  next 
section  treating  of  the  cord  as  a  path  of  conduction  to  and  from 
the  brain.  But  attention  may  be  called  here  to  some  of  the  gen- 


154  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

eral  results  obtained  by  Goltz  *  in  some  remarkable  experiments 
in  which  the  entire  cord  was  removed  with  the  exception  of  the 
cervical  region  and  a  small  portion  of  the  upper  thoracic.  In 
making  this  experiment  it  was  necessary  to  perform  the  operation 
in  several  steps.  That  is,  the  cord  was  first  sectioned  in  the  upper 
thoracic  region  and  then  in  successive  operations  the  lower  tho- 
racic, lumbar,  and  sacral  regions  were  removed  completely.  Very 
great  care  was  necessary  in  the  treatment  of  the  animals  after 
these  operations,  but  some  survived  and  lived  for  long  periods, 
the  digestive,  circulatory,  and  excretory  organs  performing  their 
functions  in  a  normal  manner.  The  muscles  of  the  hind  limbs 
and  trunk,  however,  underwent  complete  atrophy,  owing  to  the 
destruction  of  their  motor  nerves.  The  blood-vessels  also  were 
paralyzed  after  the  first  operations,  but  gradually  their  muscu- 
lature again  recovered  tone,  showing  that,  although  under  normal 
conditions  the  tonic  contraction  of  the  vessels  is  under  the  in- 
fluence of  nerves  arising  from  the  cord,  this  tone  may  be  re-estab- 
lished in  time  after  the  severance  of  all  spinal  connections.  Some 
of  the  specific  results  of  these  experiments,  bearing  upon  the  re- 
flexes of  defecation,  micturition,  and  parturition,  will  be  described 
later.  Attention  may  be  called  here  to  the  general  results 
illustrating  the  general  functions  of  the  cord. 

In  the  first  place,  there  was,  of  course,  a  total  paralysis  of  volun- 
tary movement  in  the  muscles  innervated  normally  through  the 
parts  of  the  cord  removed,  and  a  complete  loss  of  sensation  in  the 
same  regions,  particularly  of  cutaneous  and  muscular  sensibility. 
In  the  second  place,  the  visceral  organs,  including  the  blood-vessels, 
were  shown  to  be  much  more  independent  of  the  direct  control  of 
the  central  nervous  system.  While  these  organs  in  the  experiments 
under  consideration  were  still  in  connection  with  the  sympathetic 
ganglia  and  in  part  with  the  brain  through  the  vagi,  still  their 
connections  with  the  central  nervous  system,  particularly  as 
regards  their  sensory  paths  and  the  innervation  of  the  blood-vessels, 
were  in  largest  part  destroyed.  The  immediate  effect  of  this 
destruction  would  have  been  the  death  of  the  animal  if  the  care 
of  the  observer  had  not  replaced,  in  the  beginning,  the  normal 
control  exercised  by  the  nervous  system  through  the  spinal  nerves; 
but  later  this  careful  nursing  was  not  required.  While  these  organs, 
therefore,  are  capable  of  a  certain  amount  of  independent  activity 
and  co-ordination,  they  are  normally  controlled  through  the  various 
reflex  activities  of  the  brain  and  cord.  In  the  third  place,  it  is 
noteworthy  that  the  adaptability  of  the  cordless  portion  of  the 
animal  was  distinctly  less  than  normal.  Its  power  of  preserving  a 

*  Goltz  and  Ewald,  "Pfliiger's  Archiv  fur  die  gesammte  Physiologie,"  63, 
362,  1896. 


KEFLEX    ACTIONS.  155 

constant  body  temperature  was  more  limited  than  in  the  normal 
animal,  and  the  susceptibility  to  inflammatory  disturbances  in  the 
visceral  organs  was  greatly  increased.  It  seems  evident,  from  these 
facts,  that,  although  the  animal  was  living,  its  power  of  adaptation  to 
marked  changes  in  the  external  or  internal  environment  was  greatly 
lessened,  and  this  fact  illustrates  well  the  great  general  importance 
of  the  spinal  cord  and  brain  as  reflex  centers  controlling  the  nutri- 
tion and  co-ordinated  activities  of  the  body  tissues  and  organs. 
This  control  is  necessary  under  normal  conditions  for  the  success- 
ful combination  of  the  activities  of  the  various  organs.  A  large 
part  of  this  control  is  doubtless  dependent  upon  the  regulation  of 
the  blood  supply  to  the  various  organs.  The  mechanism  by  which 
this  is  effected  and  the  parts  played  by  the  cord  and  the  brain 
(medulla  oblongata),  respectively,  will  be  described  in  the  section 
on  Circulation. 

Knee-jerk. — Knee-jerk  or  knee-kick  is  the  name  commonly 
given  to  the  jerk  of  the  foot  when  a  light  blow  is  struck  upon  the 
patellar  ligament  just  below  the  knee.  The  jerk  of  the  foot  is 
due  to  a  contraction  of  the  quadriceps  femoris  muscle.  Accord- 
ing to  Sherrington,  the  parts  of  this  muscular  mass  chiefly 
concerned  are  the  m.  vastus  medialis  and  m.  vastus  intermedius. 
In  order  to  obtain  the  muscular  response  it  is  usually  neces- 
sary to  put  the  quadriceps  under  some  tension  by  flexion  of  the 
leg.  This  end  is  achieved  most  readily  by  crossing  the  knees 
or  by  allowing  the  leg  to  hang  freely  when  sitting  on  the  edge 
of  a  bench  or  table.  Under  such  circumstances  the  jerk  is 
obtained  in  the  great  majority  of  normal  persons,  and  this 
fact  has  made  it  an  important  diagnostic  sign  in  many  diseases 
of  the  spinal  cord.  The  importance  of  the  reaction  for  such 
purposes  was  first  brought  out  by  the  v  ork  of  Erb  and  Westphal  * 
in  1875. 

Reinforcement  of  the  Knee-jerk. — It  was  first  shown  by 
Jendrassik  (1883)  that  the  extent  of  the  jerk  may  be  greatly  aug- 
mented if,  at  the  time  the  blow  is  struck  upon  the  tendon,  a  strong 
voluntary  movement  is  made  by  the  individual,  such  as  squeezing 
the  hands  together  tightly  or  clenching  the  jaws.  This  phenomenon 
was  studied  carefully  in  this  country  by  Mitchell  and  Lewis,  f  who 
ascertained  that  a  similar  augmentation  may  be  produced  by  giving 
the  individual  a  simultaneous  sensory  stimulation.  They  desig- 
nated the  phenomenon  as  a  reinforcement,  and  this  name  is  gen- 
erally employed  by  English  writers,  although  occasionally  the  term 
"Bahnung,"  introduced  by  Exner  to  describe  a  similar  phenom- 
enon, is  also  used.  It  is  found  that  by  a  reinforcement  the  knee- 

*  Erb  and  Westphal,  "Archiv  f.  Psychiatric,"  1875,  vol.  v. 

t  Mitchell  and  Lewis,  "American  Journal  of  Med.  Sciences,"  92,  363, 1886. 


156 


PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 


jerk  may  be  demonstrated  in  some  individuals  in  whom  the  ordi- 
nary blow  upon  the  tendon  fails  to  elicit  a  response.  Bowditch  and 
Warren*  studied  the  phenomenon  of  reinforcement  and  brought  out 
a  fact  of  very  great  interest.  They  studied  especially  the  time 
interval  between  the  blow  upon  the  tendon  and  the  reinforcing  act 
and  found  that  if  the  latter  preceded  the  blow  by  too  great  an  inter- 
val then,  instead  of  an  augmentation  of  the  jerk,  there  was  a  dimi- 
nution which  they  designated  as  negative  reinforcement  or  inhi- 
bition. This  inhibiting  effect  began  to  appear  when  the  reinforcing 
act  (hand-squeeze)  preceded  the  blow  by  an  interval  of  from  0.22 
to  0.6  sec.;  and  the  maximum  inhibiting  effect  was  obtained  at  an 


40- 
30- 
20- 
10- 


mm 


10- 


20- 


30- 


NORMAL 


TIME 


o.4" 


0.7- 


LCT 


L7- 


Fig.  70. — Showing  in  millimeters  the  amount  by  which  the  "reinforced"  knee-kick 
varied  from  the  normal,  the  level  of  which  is  represented  by  the  horizontal  line  at  0,  "nor- 
mal." The  time  intervals  elapsing  between  the  clenching  of  the  hands  (which  constituted 
the  reinforcement)  and  the  tap  on  the  tendon  are  marked  below.  The  reinforcement  is 
greatest  when  the  two  events  are  nearly  simultaneous.  At  an  interval  of  0.4  sec.  it 
amounts  to  nothing;  during  the  next  0.6  sec.  the  height  of  the  kick  is  actually  diminished, 
while  after  an  interval  of  1  sec.  the  negative  reinforcement  tends  to  disappear;  and  when 
1.7  sec.  is  allowed  to  elapse  the  height  of  the  kick  ceases  to  be  affected  by  the  clenching  of 
the  hands.— (Bowditch  and  Warren.) 

interval  of  from  0.6  to  0.9  sec.  Beyond  this  point  the  effect  became 
less  noticeable,  and  at  an  interval  of  1.7  to  2.5  sec.  the  reinforcing 
act  had  no  influence  at  all  upon  the  jerk.  These  relations  are 
shown  in  the  accompanying  curve  (Fig.  70).  These  authors  con- 
firmed also  the  fact  that  a  sensory  stimulus,  such  as  a  gentle  blast 
of  air  on  the  conjunctiva  or  the  knee,  may  reinforce  the  jerk.  The 
physiological  explanation  of  the  reinforcement,  negative  and  posi- 
tive, is  a  matter  of  inference  only,  but  the  view  usually  held  is  that 
it  is  due  to  "overflow."  That  is,  many  facts,  such  as  strychnin 
tetanus,  indicate  that  the  neuromuscular  machinery  of  the  entire 
central  nervous  system  is  more  or  less  directly  connected  and  that 


*  Bowditch  and  Warren,  "Journal  of  Physiology,"  2,  25,  1890. 


REFLEX    ACTIONS.  157 

functional  activity  at  one  part  may  influence  the  irritability  of  the 
remainder,  either  in  the  direction  of  reinforcement  or  inhibi- 
tion. We  may  conceive,  therefore,  that  when  the  hands  are 
squeezed,  the  motor  impulses  sent  down  from  the  cortex  of  the 
brain  to  the  upper  portion  of  the  cord  overflow  to  some  extent, 
sufficient  at  least  to  alter  the  irritability  of  the  other  motor  neurons 
in  the  cord.  Experimental  stimulation  of  the  cortex  has  given 
similar  results.  Exner*  found  that  when  the  motor  center  for  the 
foot  in  the  cortex  of  a  rabbit  was  stimulated,  the  stimulation,  even 
if  too  weak  to  be  effective  itself,  caused  an  increase  in  the  contraction 
brought  about  reflexly  by  a  simultaneous  stimulation  of  the  skin 
of  the  paw,  and  furthermore ,  if  these  stimuli  were  so  reduced  in 
strength  that  each  was  ineffective,  then  when  applied  together  a 
contraction  was  obtained.  In  this  case  an  ineffective  stimulus 
from  the  cortex  reaching  the  spinal  cord  increased  the  irritability 
of  the  motor  centers  there  so  that  a  simultaneous  reflex  stimulus 
from  the  foot,  ineffective  in  itself,  became  effective. 

Is  the  Knee-jerk  a  Reflex?— The  most  interesting  question 
in  this  connection  is  whether  the  jerk  is  a  true  reflex  act  or  is  due 
to  a  direct  mechanical  stimulation  of  the  muscle.  Opinions  have 
been  divided  upon  this  point.  Those  who  believe  that  the  jerk  is  » 
reflex  lay  emphasis  upon  the  undoubted  fact  that  the  integrity  of 
the  reflex  arc  is  absolutely  essential  to  the  response.  The  quad- 
riceps receives  its  motor  and  sensory  fibers  through  the  femoral 
nerve,  and  pathological  lesions  upon  man  as  well  as  direct 
experimental  investigation  upon  monkeys  prove  that  if  either  the 
posterior  or  anterior  roots  of  the  third  and  fourth  lumbar  spinal 
nerves  are  destroyed  the  knee-jerk  disappears  entirely.  The  oppo- 
nents of  the  reflex  view  explain  this  fact  by  the  theory  that  in 
order  for  the  quadriceps  to  respond  it  must  be  in  a  condition 
of  tonus.  This  tonus  depends  upon  the  reflex  arc,  the  sensory 
impulses  from  the  muscle  serving  to  keep  it  in  that  condition 
of  subdued  contraction  known  as  tone.  On  this  view  destruc- 
tion of  the  reflex  arc  renders  the  muscle  less  irritable,  so  that  it 
will  not  respond  by  a  contraction  to  the  sudden  mechanical  exten- 
sion or  pull  caused  by  the  blow  on  the  tendon.  The  adherents  of 
this  view  lay  emphasis  upon  two  facts:  First,  the  knee-jerk  is  a 
simple  contraction,  and  not  a  tetanus,  and,  generally  speaking, 
the  motor  centers  of  the  cord  discharge  a  series  of  impulses  when 
stimulated.  In  answer  to  this  objection  it  may  be  said  that 
while  muscular  contractions  produced  reflexly  are  usually 
tetanic,  it  does  not  follow  that  this  is  invariably  the  case.  Sher- 
ringtonf  has  shown,  for  instance,  that  an  undoubted  reflex 

*  Exner,  "Archiv  f .  die  gesammte  Physiologic,"  27,  412,  1882. 

t  Sherrington,  "The  Integrative  Action  of  the  Nervous  System,"  1906. 


158  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

designated  by  him  as  the  " extensor  thrust,"  which  also  involves 
the  extensor  muscles  of  the  hind  leg,  is  very  short  lasting,  requir- 
ing perhaps  only  £  sec.,  and  judged  by  this  standard  is  as  much 
of  a  simple  contraction  as  the  knee-jerk.  The  " extensor  thrust" 
is  a  sharp  contraction  of  the  extensor  muscles  of  the  hind  leg 
aroused  by  pressure  upon  the  plantar  surface  of  the  hind  foot. 
On  the  frog  also  a  single  stimulus  applied  to  the  central  end  of  the 
divided  sciatic  nerve  will  call  forth  a  reflex  contraction,  which  is  a 
twitch,  and  not  a  tetanus.  Second,  the  time  for  the  jerk — that  is, 
the  interval  between  the  stimulus  and  the  response — is  too  short 
for  a  reflex.  The  determination  of  this  time  has  been  attempted  by 
many  observers  for  the  purpose  of  deciding  the  controversy,  but 
unfortunately  the  results  have  been  lacking  in  uniformity,  although 
the  best  results  from  man  indicate  a  latency  between  stimulus  and 
response  of  0.023  sec.  after  deducting  the  latent  period  of  the  mus- 
cle icself.  Applegarth,  making  use  of  a  dog  with  a  severed  spinal 
cord,  obtained  for  the  time  of  the  knee-jerk  an  interval  of  0.014  to 
0.02  sec. ;  Waller  and  Gotch,  using  the  rabbit,  found  the  time  to  be 
only  0.008  to  0.005  sec.  Other  figures  would  appear  to  indicate 
that  the  latent  period  is  shorter  the  smaller  the  animal,  a  fact  which 
in  itself  would  imply  that  some  factor  other  than  the  latency  of 
the  muscle  itself  enters  into  the  time  required.  And  if  we  accept 
the  newer  figures  in  regard  to  the  velocity  of  the  nerve  impulse  in 
mammalian  nerves  at  the  body  temperature  (see  p.  Ill),  there 
would  seem  to  be  sufficient  time  in  all  cases  for  the  impulse  to  get 
to  the  cord  and  back.  Several  observers*  have  attempted  to 
determine  the  time  intervening  between  stimulus  and  response 
by  using  the  string  galvanometer  to  indicate  the  electrical  response 
in  the  muscle,  instead  of  attempting  to  record  the  contraction 
itself.  According  to  Snyder,  the  time  interval  lies  between  0.0113 
and  0.015  sec.,  while  Hoffmann's  results  give  an  interval  of  0.019 
to  0.024  sec.  The  calculations  of  both  observers  indicate  that  the 
time  is  sufficient  for  a  reflex,  and  much  too  long  for  a  direct  excita- 
tion. In  the  case  of  the  Achilles  jerk,  Hoffmann  finds  that  it  may 
be  liberated  by  electrical  stimulation  of  the  n.  tibialis  and  that 
under  these  circumstances  there  is  first  a  deflection  of  the  galvano- 
meter, due  to  direct  stimulation  of  the  gastrocnemius  through 
its  motor  nerve,  and  this  is  followed  later  by  a  second  deflection,  dut 
to  reflex  stimulation.  This  latter  accords  in  time  interval  with  the 
Achilles  jerk,  and  gives  a  new  proof  that  the  phenomenon  is  a 
genuine  reflex.  In  view  of  these  facts  it  would  seem  to  be  safe 
to  conclude  that  the  knee-kick  and  similar  phenomena  are  reflexes 

*  Snyder,  "American  Journal  of  Physiology,"  26,  474,  1910.    Hoffmann, 
"Archiv  f.  Physiologic,"  1910,  223. 


REFLEX    ACTIONS. 


159 


but  reflexes  in  which  a  single  nerve  impulse  is  sent  out  from  the 
cord,  causing  a  simple  contraction  in  the  muscle  affected. 

Conditions  Influencing  the  Extent  of  the  Knee-jerk.— The 
effect  of  various  normal  conditions  upon  the  knee-jerk  has  been 
studied  by  a  number  of  observers,  particularly  by  Lombard.*  The 
results  are  most  interesting  in  that  they  indicate  very  clearly  that 
the  irritability  of  the  spinal  cord  varies  with  almost  every  marked 
change  in  mental  activity.  During  sleep  the  jerk  disappears 
and  in  mental  conditions  of  a  restful  character  its  extent  is  relatively 
small.  In  conditions  of  mental  excitement  or  irritation,  on  the 
contrary,  the  jerk  becomes  markedly  increased.  Lombard  ob- 
served also,  in  his  own  case,  a'  daily  rhythm,  which  is  represented 
in  the  chart  given  in  Fig.  71.  It  would  seem  from  his  experiments 


April  OtH  1887 


Fig.  71. — Lombard's  figure  to  indicate  the  daily  rhythm  in  the  extent  of  the  knee- 
jerk  and  the  effect  of  mental  stimuli.  The  ordinates  (0-110)  represent  the  extent  of  the 
kick  in  millimeters.  Each  dot  represents  a  separate  kick,  while  the  heavy  horizontal  line 
gives  the  average  extent  for  the  period  indicated. 


that  the  extent  of  the  knee-jerk  is  a  sensitive  indicator  of  the 
relative  state  of  irritability  of  the  nervous  system:  "The  knee- 
jerk  is  increased  and  diminished  by  whatever  increases  and  di- 
minishes the  activity  of  the  central  nervous  system  as  a  whole." 
This  general  fact  is  supported,  especially  as  regards  mental  activity, 
by  observations  on  other  similar  mechanisms, — such,  for  instance, 
as  the  condition  of  the  nervous  centers  controlling  the  bladder. 


*  Lombard,  "The  American  Journal  of  Psychology,"  1887,  p.  1. 
also  article  "Knee-jerk"  (Warren),  "Wood's  Ref.    Handbook  of  Med. 


See 
Sci< 


ences. 


160  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

Use  of  the  Knee-jerk  and  Spinal  Reflexes  as  Diagnostic 
Signs. — The  fact  that  the  knee-jerk  depends  on  the  integrity  of 
the  reflex  arc  in  the  lumbar  cord  has  made  it  useful  as  a  diagnostic 
indication  in  lesions  of  the  cord,  particularly,  of  course,  for  the 
lumbar  region.  It  is  mainly  on  account  of  its  practical  value  and 
the  ease  with  which  it  is  ordinarily  obtained  that  the  phenom- 
enon has  been  studied  so  extensively.  In  the  disease  known  as 
progressive  locomotor  ataxia  the  posterior  root  fibers  in  the  pos- 
terior columns  in  the  lumbar  region  are  affected,  and,  as  a  con- 
sequence, the  jerk  is  diminished  or  abolished  altogether  according 
to  the  stage  of  the  disease.  So  also  lesions  affecting  the  anterior 
horns  of  the  gray  matter  will  destroy  the  reflex  by  cutting  off  the 
motor  path,  while  in  other  cases  lesions  in  the  brain  or  the  lateral 
columns  of  the  cord  affecting  the  pyramidal  system  of  fibers  may 
be  accompanied  by  an  exaggeration  of  this  and  similar  reflexes. 
This  latter  fact  agrees  with  the  experimental  results  (see  p.  147) 
upon  ablation  of  the  brain.  After  such  operations  in  the  frog 
and  lower  mammals  at  least  the  spinal  reflexes  may  show  a  marked 
increase.  Interruption  of  the  descending  connections  between  brain 
and  cord  at  any  point,  therefore,  may  be  accompanied  by  a  strik- 
ing increase  in  sensitiveness  of  the  spinal  reflexes.  The  explana- 
tion usually  given  is  that  the  inhibitory  influences  of  the  brain 
centers  upon  the  cord  are  thereby  weakened  or  destroyed. 

Other  Spinal  Reflexes. — Various  other  distinctive  reflexes 
through  the  spinal  cord  may  be  obtained  readily,  and  since  the 
motor  cells  concerned  lie  at  different  levels  in  the  cord  the 
•  presence,  absence,  or  modified  character  of  these  reflexes  has 
been  used  frequently  for  diagnostic  purposes.  In  the  first 
place  there  are  a  number  of  so-called  deep  reflexes  which  may 
be  aroused  by  sensory  stimulation  of  parts  beneath  the  skin, 
such  as  the  tendons,  ligaments,  and  periosteum.  Almost  any 
tendon  if  stimulated  mechanically  may  give  a  jerk  of  the  cor- 
responding muscle,  just  as  in  the  case  of  the  knee-kick.  Such 
reactions  have  been  described  and  used  in  the  case  of  the  wrist- 
jerk,  the  jaw-jerk,  the  Achilles-jerk,  etc.  The  last  named  is 
obtained  by  putting  the  foot  into  a  position  of  dorsiflexion  and 
then  tapping  the  tendo  calcaneus  (Achillis).  The  result  is  a 
contraction  of  the  gastrocnemius,  causing  plantar  flexion  of  the 
foot.  A  variation  of  this  reflex  is  the  phenomenon  known  as 
ankle  clonus.  This  is  obtained  by  giving  a  quick  forcible 
dorsiflexion  to  the  foot  thus  putting  the  tendon  and  muscle 
under  a  sudden  mechanical  strain.  In  some  cases  there  results 
a  rhythmical  series  of  contractions  of  the  gastrocnemius.  A 
second  group  of  reflexes  may  be  obtained  by  stimulation  of 
special  points  on  the  skin,  the  cutaneous  reflexes.  For  example, 


Acusticus 
Vestibuiaris 

Gustos 
(cum  Trigemino) 

Pharynx 


ulla 


Musculi  faciei 
Mm.  pharyngis,  palati 
Mm.  laryngis 
Mm.  linguae 


Larynx,  Trachea 
Intestina 

(ThoraUbdomen) 

Regio  occipitalis 
Regio  colli 
Regio  nuchae 
Regio  humeri 
Regio  Nervi  radialis 
Regio  N.  mediani 
Regio  N.  ulnaris 


Sternocleidomastoiueus 
Musculi  colli  et  nuchae 
Scaleni,  Splenius 

Cucullaris 

Rhomboidei,  Levator  anguli  scapulae 


Supra-,  infraspinatus 

,  Supinator  longus 


cruris 


anterior 


Serratus  anticus,  Supinator  brevis 

Pectoralis  major  (portiociavicui.) 

Teres  minor 

Prate*  Brachialis  internus 

Triceps 

Extensores  carpi  et  (Jigilor.  long! 

Pectoralis  major  (portio  costalis] 
Latissimus  dorsiteres  major 

Flexores  carpi  et  digitor.  longi 

Eitensores  pollicis 
Interossei  lumbricales 
Thenar  Hpthenar 


(  posterior 

I   mediana 

'    lateralis 

Scrotum,  penis, 

Perineum 

Vesica 


Sartorius 

Quadriceps  temoris 

Glutaei,  tensor  fasc.lat. 

Adductores  femoris 
Abductores  temoris 
Tibialis  anticus 
Gastrocnemius,  Soleus 
Biceps  Semitendi-Semimembranosus 
Obturator,  pyriformis,  quadratic  femor. 


Peronei 
Flexores  digitorum 


Anus 


Mm.  vesicates 
Mm.  rectales 


Fig.   72. 


REFLEX    ACTIONS.  161 

the  plantar  reflex,  which  consists  in  a  flexion  of  the  toes  when  the 
sole  of  the  foot  is  stimulated  by  tactile  or  painful  stimuli.  Under 
pathological  conditions  which  involve  a  lesion  of  the  pyramidal 
tracts  in  the  cord  this  reflex  is  altered,  the  great  toe  being 
extended  instead  of  flexed  (Babinski's  phenomenon).  The 
cremasteric  reflex  consists  in  a  contraction  of  the  cremasteric 
muscle  which  raises  the  testis.  It  follows  from  stimulation  of 
the  skin  on  the  inner  side  of  the  thigh  at  the  level  of  the  scrotum. 
The  location  of  the  motor  centers  of  these  and  other  similar 
reflexes  is  shown  in  the  accompanying  illustration  (Fig.  72). 

11 


CHAPTER  VIII. 
THE  SPINAL  CORD  AS  A  PATH  OF  CONDUCTION. 

In  addition  to  the  varied  and  important  functions  performed 
by  the  cord  as  a  system  of  reflex  centers  controlling  the  activities 
of  numerous  glands  and  visceral  organs  as  well  as  the  so-called 
voluntary  muscles,  it  is  physiologically  most  important  as  a  path- 
way to  and  from  the  brain.  All  the  fibers,  numbering  more  than 
half  a  million,  that  enter  the  cord  through  the  posterior  roots  of 
the  spinal  nerves  bring  in  afferent  impulses,  which  may  be  continued 
upward  by  definite  tracts  that  end  eventually  in  the  cortex  of  the 
cerebrum,  the  cerebellum,  or  some  other  portion  of  the  brain.  On 
the  other  hand,  many  of  the  efferent  impulses  originating  reflexly 
or  otherwise  in  different  parts  of  the  brain  are  conducted  downward 
into  the  cord  to  emerge  at  one  or  another  of  the  anterior  roots  of 
the  spinal  nerves.  The  location  and  extent  of  these  ascending  and 
descending  paths  form  a  part  of  the  inner  structure  of  the  cord, 
which  is  most  important  practically  in  medical  diagnosis  and  which 
has  been  the  subject  of  a  vast  amount  of  experimental  inquiry  in 
physiology,  anatomy,  pathology,  and  clinical  medicine.  In  working 
out  this  inner  architecture  the  neuron  conception  has  been  of  the 
greatest  value,  and 'the  results  are  usually  presented  in  terms  of 
these  interconnecting  units. 

The  Arrangement  and  Classification  of  the  Nerve  Cells 
in  the  Gray  Matter  of  the  Cord. — Nerve  cells  are  scattered 
throughout  the  gray  matter  of  the  cord,  but  are  arranged  more 
or  less  distinctly  in  groups  or,  considering  the  longitudinal  aspect 
of  the  cord,  in  columns  the  character  of  which  varies  somewhat  in 
the  different  regions.  From  the  standpoint  of  physiological  anatomy 
these  cells  may  be  grouped  into  four  classes:  (1)  The  anterior 
root  cells,  clustered  in  the  anterior  column  of  gray  matter  (1,  Fig. 
73).  The  axons  of  these  cells  pass  out  of  the  cord  almost  at  once 
to  form  the  anterior  or  motor  roots  of  the  spinal  nerves.  (2)  The 
tract  cells,  so  called  because  their  axons  instead  of  leaving  the  cord 
by  the  spinal  roots  enter  the  white  matter  and,  passing  upward 
or  downward,  help  to  form  the  tracts  into  which  this  white  matter 
may  be  divided  (2  and  3  of  Fig.  73).  These  tract  cells  are  found 
throughout  the  gray  matter,  and,  according  to  the  side  on  which  the 
axon  enters  into  a  tract,  they  maybe  divided  into  three  subgroups: 
(a)  Those  whose  axons  enter  the  white  matter  on  the  same  side  of 

162 


SPINAL    CORD    AS    A    PATH    OF    CONDUCTION. 


163 


the  cord,  the  tautomeric  tract  cells  of  Van  Gehuchten.  (6) 
Those  whose  axons  pass  through  the  anterior  white  commissure 
and  thus  reach  the  tracts  in  the  white  matter  of  the  other  side. 
These  are  known  as  commissural  cells  or  the  heteromeric  tract 
cells  of  Van  Gehuchten.  They  form  one  obvious  means  for  crossed 
conduction  in  the  cord,  (c)  Those  whose  axons  divide  into  two, 
one  passing  into  the  white  matter  of  the  same  side,  the  other  pass- 
ing by  way  of  the  anterior  commissure  to  reach  the  white  matter 
of  the  opposite  side — the  hecateromeric  tract  cells  of  Van  Gehuch- 
ten. (3)  The  Golgi  cells  of  the  second  type — that  is,  cells  whose 


Dorsal 


l/etttral 


Fig.  73. — Schema  of  the  structure  of  the  cord. — After  Lenhossek.)  On  the  right  the 
nerve  cells;  on  the  left  the  entering  nerve  fibers.  Right  side:  1,  Motor  cells,  anterior 
column,  giving  rise  to  the  fibers  of  the  anterior  root;  2,  tract  cells  whose  axons  pass  into 
the  white  matter  of  the  anterior  and  lateral  funiculi;  2,  commissural  cells  whose  axons  pass 
chiefly  through  the  anterior  commissure  to  reach  the  anterior  funiculi  of  the  other  side; 
4,  Golgi  cells  (second  type),  whose  axons  do  not  leave  the  gray  matter;  5,  tract  cells  whose 
axons  pass  into  the  white  matter  of  the  posterior  funiculi.  Left  side:  1,  Entering  fibers 
of  the  posterior  root,  ending,  from  within  outward,  as  follows:  Clarke's  column,  posterior 
column  of  opposite  side,  anterior  column  same  side  (reflex  arc),  lateral  column  of  same  side, 
posterior  column  of  same  side;  2,  collaterals  from  fibers  in  the  anterior  and  lateral  funiculi, 
3,  collaterals  of  descending  pyramidal  fibers  ending  around  motor  cells  in  anterior  column. 

axons  divide  into  a  number  of  small  branches  like  those  of  a 
dendrite.  The  axons  of  these  cells,  therefore,  do  not  become 
medullated  nerve  fibers;  they  take  no  part  in  the  formation  of 
the  spinal  roots  or  the  tracts  of  white  matter  in  the  cord,  but 
terminate  diffusely  within  the  gray  matter  itself.  (4)  The  pos- 
terior root  cells  lying  toward  the  base  of  the  anterior  columns. 
These  cells  have  been  demonstrated  in  some  of  the  lower  verte- 
brates (petromyzon — chick  embryo),  but  their  existence  in  the 
mammal  is  still  a  question  in  some  doubt;  their  axons  pass  out 
from  the  cord  by  the  posterior  root  and  they  form  the  anatomical 
evidence  for  the  view  that  the  posterior  roots  may  contain  some 
efferent  fibers.  Some  of  the  groups  of  tract  cells  have  been  given 
special  names — such,  for  instance,  as  the  dorsal  nucleus  (Clarke's 


164  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

column).  This  group  of  cells  lies  at  the  inner  angle  of  the 
posterior  column  of  gray  matter  (5,  Fig.  76),  and  forms  a  column 
usually  described  as  extending  from  the  middle  lumbar  to  the 
upper  dorsal  region.  The  axons  from  these  cells  pass  to  the 
dorsal  margin  of  the  lateral  funiculi  on  the  same  side  to  con- 
stitute an  ascending  tract  of  fibers  known  as  the  tract  of  Flechsig, 
or  the  fasciculus  cerebellospinalis. 

General  Relations  of  the  Gray  and  White  Matter  in  the 
Cord. — Cross-sections  of  the  cord  at  different  levels  show  that 
the  relative  amounts  of  gray  and  white  matter  differ  considerably 
at  different  levels,  so  that  it  is  quite  possible  to  recognize  easily 
from  what  region  any  given  section  is  taken.  At  the  cervical  and 
the  lumbar  enlargements  the  amounts  of  both  gray  and  white 
matter — that  is,  the  total  cross-area  of  the  cord — show  a  sudden 


•White  matter.  Gray  matter.          DiHre  secrion. 

100 


80 
60 
40 
80 


^Composite  curves  based  on  4  Cases. 


II  BIT  TUMI  n  m  IT    t     u    YJI    mi    ix    x    an    i  mmmiitwm 

Fig.  74. — Curves  to  show  the  relative  areas  of  the  gray  and  white  matter  of  the  spinal 
cord  at  different  levels. — (Donaldson  and  Davis.)  The  Roman  numerals  along  the  abscissa 
represent  the  origin  of  the  different  spinal  nerves. 

increase  owing  to  the  larger  number  of  fibers  arising  at  these  levels. 
The  white  matter,  and  therefore  the  total  cross-area,  shows  also 
a  constant  increase  from  below  upward,  due  to  the  fact  that  in 
the  upper  regions  many  fibers  exist  that  have  come  into  the  cord 
at  a  lower  level  or  from  the  brain,  those  from  the  latter  region  being 
gradually  distributed  to  the  spinal  nerves  as  we  proceed  downward. 
In  the  accompanying  figure  a  curve  is  presented  showing  the  cross- 
area  of  the  cord  and  the  relative  amounts  of  gray  and  white  matter 
at  each  segment. 

Tracts  in  the  White  Matter  of  the  Cord,  Methods  of  Deter- 
mining.— The  separation  of  the  medullated  fibers  of  the  cord 
into  distinct  tracts  of  fibers  possessing  different  functions  has 
been  accomplished  in  part  by  the  combined  results  of  investiga- 
tions in  anatomy,  physiology,  and  pathology.  The  two  methods 
that  have  been  employed  most  frequently  and  to  the  best  advan- 
tage are  the  method  of  secondary  degeneration  (Wallerian  degen- 
eration) and  the  method  of  myelinization.  The  method  of  second- 
ary degeneration  depends  upon  the  fact  that,  when  a  fiber  is  cut 
off  from  its  cell  of  origin,  the  peripheral  end  degenerates  in  a  few 
days.  If,  therefore,  a  lesion,  experimental  or  pathological,  is  made 


SPINAL    CORD    AS    A    PATH    OF    CONDUCTION.  165 

in  the  cord  at  any  level,  those  fibers  that  are  affected  undergo 
degeneration:  those  with  their  cells  below  the  lesion  degenerate  up- 
ward, and  those  with  their  cells  above  the  lesion  degenerate  down- 
ward. According  to  the  law  of  polarity  of  conduction  in  the  neuron 
a  descending  degeneration  in  the  cord  indicates  motor  or  efferent 
paths  as  regards  the  brain,  and  ascending  degeneration  indicates 
sensory  or  afferent  paths.  It  is  obvious  that  localized  lesions  can 
be  used  hi  this  way  to  trace  definite  groups  of  fibers  through  the  cord. 
If,  for  instance,  one  exposes  and  cuts  the  posterior  roots  in  one  or 
more  of  the  lumbar  nerves,  the  portions  of  the  fibers  entering  the 
cord  will  degenerate,  and  the  path  of  some  of  these  fibers  may  be 
traced  in  this  way  upward  to  the  medulla.  The  degenerated  fibers 
may  be  revealed  histologically  by  the  staining  methods  of  Weigert 
or  of  Marchi.  The  latter  method  (preservation  in  Miiller's  fluid, 
staining  in  osmic  acid  and  Miiller's  fluid)  has  proved  to  be  espe- 
cially useful;  the  degenerated  fibers  during  a  certain  period  give 
a  black  color  with  this  liquid,  owing  probably  to  the  splitting  up 
of  the  lecithin  in  the  myelin  and  the  liberation  of  the  fat  from  its 
combination  with  the  other  portions  of  the  molecule.*  The  mye- 
linization  method  was  introduced  by  Flechsig.  It  depends  upon 
the  fact  that  in  the  embryo  the  nerve  fibers  as  first  formed  have 
no  myelin  sheath,  and  that  this  easily  detected  structure  is  in  the 
central  nervous  system  assumed  at  about  the  same  time  by  those 
bundles  or  tracts  of  fibers  that  have  a  common  course  and  func- 
tion. By  this  means  the  origin  and  termination  of  certain  tracts 
may  be  worked  out  in  the  embryo  or  shortly  after  birth.  The 
well-known  system  of  pyramidal  fibers,  for  instance,  is  clearly 
differentiated  in  the  embryo  late  in  intra-uterine  life  or  at  birth, 
owing  to  the  fact  that  the  fibers  composing  it  have  not  at  that 
time  acquired  their  myelin  sheaths.  Flechsig  assumes  that  the 
development  of  the  myelin  marks  the  completed  structure  of  the 
nerve  fiber  and  indicates,  therefore,  the  time  of  its  entrance  into 
full  functional  activity. 

General  Classification  of  the  Tracts. — The  tracts  that  have 
been  worked  out  in  the  white  matter  of  the  cord  have  been  classified 
in  several  ways.  We  have,  in  the  first  place,  the  division  into  as- 
cending and  descending  tracts.  This  division  rests  upon  the  fact 
that  the  axon  conducts  its  impulses  away  from  the  cell  of  origin,  and 
consequently  those  neurons  whose  axons  extend  upward  toward  the 
higher  parts  of  the  cord  or  brain  are  designated  as  ascending,  since 
normally  the  impulses  conducted  by  them  take  this  direction.  They 
constitute  the  afferent  or  sensory  paths,  and  in  case  of  injury  to  the 
fiber  or  cell  the  secondary  degeneration  also  extends  upward.  The 
reverse,  of  course,  holds  true  for  the  descending  or  motor  paths. 

*  See  Halliburton,  "The  Chemical  Side  of  Nervous  Activity,"  London. 
1901;  "Croonian  Lectures." 


166  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

The  tracts  may  be  divided  also  into  long  and  short  (or  segmental) 
tracts.  The  latter  group  comprises  those  tracts  or  fibers  which 
have  only  a  short  course  in  the  white  matter,  extending  over  a  dis- 
tance of  one  or  more  spinal  segments.  Histologically  the  fibers  of 
these  tracts  take  their  origin  from  the  tract  cells  in  the  gray  matter 
of  the  cord  and  after  running  in  the  white  matter  for  a  distance  of 
one  or  more  segments  they  again  enter  the  gray  matter  to  terminate 
around  the  dendritic  processes  of  another  neuron.  These  short 
tracts  may  be  ascending  or  descending,  and  the  impulses  that  they 
conduct  are  conveyed  up  or  down  the  cord  by  a  series  of  neurons, 
each  of  whose  axons  runs  only  a  short  distance  in  the  white  matter, 
and  then  conveys  its  impulse  to  another  neuron  whose  axon  in  turn 
extends  for  a  segment  or  two  in  the  white  matter,  and  so  on. 
These  tracts  are  sometimes  described  as  association  or  short  associa- 
tion tracts,  because  they  form  the  mechanism  by  which  the  activi- 
ties of  different  segments  of  the  cord  are  brought  into  association. 
This  method  of  conduction  by  segmental  relays  involving  the  par- 
ticipation of  a  series  of  neurons  may  be  regarded  as  the  primitive 
method.  It  indicates  the  original  structure  of  the  cord  as  a  series 
of  segments,  each  more  or  less  independent  physiologically.  The 
short  tracts  in  the  mammalian  cord  lie  close  to  the  gray  matter, 
forming  the  bulk  of  what  is  known  as  the  anterior  and  lateral 
proper  fasciculi.  The  long  tracts,  on  the  contrary,  are  com- 
posed of  those  fibers,  ascending  or  descending,  which  run  a  long 
distance,  and,  in  fact,  extend  from  the  cord  to  some  part  of 
the  brain.  It  is  known,  however,  that,  although  the  tracts 
as  tracts  extend  from  brain  to  cord,  many  of  their  constituent 
fibers  may  begin  and  end  in  the  cord  or  in  the  brain,  as  the 
case  may  be.  Some  of  the  fibers  of  the  long  tracts  are,  there- 
fore, so  far  as  the  cord  is  concerned,  simply  long  association 
tracts  which  connect  different  regions — e.  g.,  cervical  and  lum- 
bar— of  the  cord  by  a  single  neuron,  as  the  short  asso- 
ciation tracts  connect  different  segments  of  the  same  region. 
It  is  said  that  in  these  long  tracts  those  fibers  that  have 
the  shortest  course  lie  to  the  inside — that  is,  nearest  to  the  gray 
matter.*  From  the  results  of  comparative  studies  of  the  different 
vertebrates  we  may  conclude  that  the  long  tracts  are  a  relatively 
late  development  in  their  phylogenetic  history,  and  that  in  the 
most  highly  developed  animals,  man  and  the  anthropoid  apes, 
these  long  tracts  are  more  conspicuous  and  form  a  larger  per- 
centage of  the  total  area  of  the  cord.  A  physiological  corollary 
of  this  conclusion  should  be  that  in  man  the  independent  activity 
of  the  cord  is  less  marked  than  in  the  lower  vertebrates,  and 
this  deduction  is  borne  out  by  facts  (see  p.  145). 

*  Sherrington  and  Lasiett,  "Journal  of  Physiology/'  29,  188,  1903;  and 
Sherrington,  ibid.,  14,  255. 


SPINAL    CORD    AS    A    PATH    OF    CONDUCTION.  167 

Specific  Designation  of  the  Spinal  Tracts. — The  tracts  that  are 
most  satisfactorily  determined  for  the  human  spinal  cord  are 
indicated  schematically  in  Fig.  75. 

They  are  named  as  follows:    In  the  posterior  funiculus, 

1.  The  fasciculus  gracilis   (column  of  Goll). 

2.  The  fasciculus  cuneatus  (column  of  Burdach). 


Fig.  75. — Schema  of  the  tracts  in  the  spinal  cord  (Kolliker)  :  0,  Fasciculus  gracilis ; 
6,  fasciculus  cuneatus ;  pc,  fasciculus  cerebrospinalis  lateralis  ;  pd,  fasciculus  cerebrospinalis 
anterior;  /,  fasciculus  cerebellospinalis  ;  gr,  fasciculus  anterolateralis  superficial) s. 

In  the  lateral  funiculus, 

1.  The  fasciculus  cerebrospinalis  lateralis,  known  also  as  the 
lateral  or  crossed  pyramidal  tract. 

2.  The  fasciculus  cerebellospinalis,  known  also  as  Flechsig's 
tract. 

3.  The  fasciculus  anterolateralis  superficial,  known  also  as 
Gowers  tract. 

4.  The  lateral  ground  bundle  (fasciculus  lateralis  proprius), 
made  up  chiefly  of  short  association  fibers. 

In  the  anterior  funiculus, 

1.  The  fasciculus  cerebrospinalis  anterior,  known  also  as  the 
direct  or  anterior  pyramidal  tract. 

2.  The  anterior  ground  bundle  (fasciculus  anterior  proprius). 
Of  these  tracts,  the  fasciculus   gracilis,  fasciculus   cuneatus, 

fasciculus  cerebellospinalis,  and  fasciculus  anterolateralis  super- 
ficialis  represent  ascending  or  sensory  paths,  while  the  lateral 
and  anterior  cerebrospinal  or  pyramidal  fasciculi  form  a  related 
descending  or  motor  path.  The  anterior  and  lateral  ground 


168 


PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 


bundles  are  composed  of  mixed  ascending  and  descending  fibers 
which  have  not  yet  been  separated  satisfactorily  into  specific  tracts, 
although  some  attempts  in  this  direction  have  been  made,  as  is 
described  briefly  below.  At  the  apex  of  the  posterior  horn,  or 
column  of  gray  matter,  there  is  found  a  small  group  of  fibers  known 
as  the  tract  of  Lissauer,  which  is  composed  apparently  chiefly  of 
ascending  fibers. 

The  Termination  in  the  Cord  of  the  Fibers  of  the  Posterior 
Root. — All  fibers  conveying  afferent  impulses  from  the  skin  of  the 
limbs  and  trunk,  from  the  muscles  and  joints,  and  from  the  vis- 
cera and  internal  mem- 
branes enter  the  cord 
through  the  posterior  roots. 
Inasmuch  as  these  roots 
are  superficially  con- 
nected with  the  pos- 
terior funiculi,  the  older 
observers  naturally  sup- 
posed that  this  portion 
of  the  white  matter  of  the 
cord  forms  the  pathway  for 
sensory  impulses  passing  to 
the  brain.  That  this  sup- 
position is  not  entirely  cor- 
rect was  proved  by  experi- 
mental physiology.  Sec- 
tion of  the  posterior  fu- 
niculi causes  little  or  no 
obvious  loss  of  sensations 
in  the  parts  below  the 
lesion.  Histological  inves- 
tigation has  since  shown 
that  only  a  portion  of  the 
fibers  entering  through  the 
posterior  root  continue  up 
the  cord  in  the  posterior 
funiculi;  some  and  indeed 
a  large  proportion  of  the 
whole  number  enter  into 
the  gray  matter  and  end 

around  tract  cells,  whence  the  path  is  continued  upward  by  the 
axons  of  these  latter  cells,  mainly  in  the  lateral  or  anterolateral 
funiculi.  The  several  ways  in  which  the  posterior  root  fibers 
may  end  in  the  cord  are  indicated  in  Fig.  76. 

The  posterior  roots  contain  fibers  of  different  diameters,  and 
those  of  smallest  size  (1)  are  found  collected  into  an  area  known 


Fig.  76. — Schema  to  show  the  terminations 
of  the  entering  fibers  of  the  posterior  root :  1, 
Fibers  entering  zone  of  Lissauer  and  terminating 
in  posterior  column;  2,  fiber  terminating  around  a 
tract  cell  whose  axon  passes  into  white  matter  of 
same  side;  3,  fiber  terminating  around  a  tract  cell 
whose  axon  passes  to  opposite  side  (commissural 
cell);  4,  fiber  terminating  around  motor  cell  of 
anterior  column  (reflex  arc);  5,  fiber  terminating 
in  tract  cell  of  dorsal  nucleus;  6,  fiber  (exog- 
enous) passing  upward  in  posterior  funiculus  to 
terminate  in  the  medulla  oblongata. 


SPINAL    CORD    AS    A    PATH    OF    CONDUCTION.  169 

as  the  tract  of  Lissauer,  lying  between  the  periphery  of  the  cord 
and  the  substantia  gelatinosa  of  the  posterior  column.  These  fibers, 
partly  medullated  and  partly  non-medullated,  terminate  chiefly 
round  the  small  cells  found  in  the  substantia  gelatinosa.*  The 
larger  fibers  of  the  root  lying  to  the  median  side  fall  into  two  groups : 
Those  lying  laterally  (2,  3,  4)  enter  the  gray  matter  of  the  posterior 
column  and  end  in  tract  cells  (2)  whose  axons  are  distributed  to 
the  same  side  of  the  cord,  or  in  tract  cells  whose  axons  (3)  pass 
to  the  other  side  through  the  anterior  white  commissure,  or  (4) 
in  the  motor  cells  of  the  anterior  column,  thus  making  a  typical 
reflex  arc.  Some  of  the  fibers  of  this  group  may  also  pass  through 
the  posterior  commissure,  to  end  in  the  gray  matter  of  the  oppo- 
site side.  The  larger  fibers  lying  nearest  to  the  median  line 
enter  the  fasciculus  cuneatus  and  run  forward  in  the  cord,  some  of 
them  (6)  continuing  upward  to  the  medulla,  and  some  of  them 
(5),  after  a  shorter  course,  turning  into  the  gray  matter  to  end  in 
the  cells  of  the  dorsal  nucleus.  The  axons  of  the  cells  in  the 
dorsal  nucleus  in  turn  pass  out  of  the  gray  matter  to  constitute 
the  ascending  path  in  the  lateral  funiculus,  known  as  the  cerebello- 
spinal  fasciculus. 

This  general  outline  of  the  mode  of  ending  in  the  cord  of  the 
fibers  of  the  posterior  root  is  complicated  further  by  the  fact  that 
these  fibers  are  supposed  to  give  off  collaterals  after  entering  the 
cord.  The  course  of  the  typical  fiber  in  the  posterior  root  is 
represented  in  Fig.  67.  According  to  this  diagram,  the  root 
fiber,  after  entering  the  cord,  makes  a  Y  or  T  division,  one  branch 
passing  downward  or  posteriorly  for  a  short  distance,  the  other, 
longer  division,  passing  upward  or  anteriorly.  Each  of  these 
main  stems  may  give  off  one  or  more  lateral  branches,  sensory 
collaterals.  A  main  stem,  therefore,  which  runs  upward  in  the 
fasciculus  cuneatus  (6)  to  terminate  in  the  medulla  oblongata 
may  give  off  collaterals  at  various  levels  which  terminate  in  the 
gray  matter  of  the  cord,  either  around  tract  cells  or  around  the 
anterior  root  cells,  forming  in  the  latter  case  a  simple  reflex  arc. 
The  existence  of  collaterals  upon  the  root  fibers  within  the  cord 
has  been  demonstrated  in  the  human  embryo,  but  we  have  little 
exact  information  concerning  their  numerical  value  in  the  adult. 
The  schema  given  in  Fig.  76  must,  therefore,  be  accepted  as  an 
entirely  diagrammatic  representation  of  the  chief  possibilities 
of  the  mode  of  ending  of  the  fibers  of  the  posterior  root  by  way 
of  their  collaterals  as  well  as  by  way  of  the  main  stems. 

Ascending    (Afferent    or    Sensory)    Paths    in    the    Posterior 

Funiculi. — The  posterior  funiculi  are  composed  partly  of  fibers 

derived  directly  from  the  posterior  roots  (6  in  schema)  and  arising, 

therefore,  from  the  cells  in  the  posterior  root  ganglia,  and  partly 

*  Hanson,  "The  American  Journal  of  Anatomy,"  16,  97,  1914. 


170 


PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 


from  fibers  that  arise 

4&  Cervical 


8tkCemcal 


2*1  Lumbar 


Fig.  77. — Diagrams  to 
show  course  of  upward  de- 
generation of  fibers  of  poste- 
rior funiculi  after  section  of 
a  number  of  posterior  roots 
of  the  nerves  forming  the 
lumbpsacral  plexus. — (Mott.) 
It  will  be  noted  that  in  the 
cervical  regions  the  degener- 
ated area  is  confined  to  the 
fasciculus  gracilis. 


from  tract  cells  in  the  gray  matter  of  the 
cord  itself.  It  is  convenient  to  speak 
of  the  former  group  as  exogenous  fibers, 
using  this  term  to  designate  nerve  fibers 
which  arise  from  cells  placed  outside 
the  cord;  and  the  latter  group  as  endo- 
genous fibers — that  is,  fibers  that  have 
their  cells  of  origin  in  the  gray  matter  of 
the  cord.  If  we  omit  a  consideration 
of  their  collaterals  the  course  of  the 
exogenous  fibers  is  easily  understood. 
They  come  into  the  cord  at  every  pos- 
terior root,  enter  into  the  fasciculus 
cuneatus,  and  pass  upward.  The  fibers 
of  this  kind  that  enter  at  the  lower 
regions,  sacral  and  lumbar,  are,  however, 
gradually  pushed  toward  the  median 
line  by  the  exogenous  fibers  entering  at 
higher  levels,  so  that  in  the  upper  tho- 
racic or  cervical  regions  the  fasciculus 
gracilis  is  composed  mainly  of  exogenous 
fibers  that  have  entered  the  cord  in  the 
lumbar  or  sacral  region.  These  fibers 
continue  upward  to  end  in  two  groups 
of  cells  that  lie  on  the  dorsal  side  of  the 
medulla  oblongata,  and  are  known, 
respectively,  as  the  nucleus  of  the 
fasciculus  gracilis  (or  nucleus  of  Goll) 
and  the  nucleus  of  the  fasciculus  cunea- 
tus (or  nucleus  of  Burdach).  Their 
path  forward  from  the  medulla  is  con- 
tinued by  new  neurons  arising  in  these 
nuclei,  and  will  be  described  later.  The 
course  of  these  fibers  in  the  cord  may  be 
shown  beautifully  by  the  method  of 
secondary  degeneration.  If  one  or  more 
of  the  posterior  roots  of  the  lumbar 
spinal  nerves  are  cut  or,  better  still,  if 
the  posterior  funiculi  are  severed  in  this 
region,  the  degeneration  will  affect  the 
exogenous  fibers  throughout  their 
course  to  the  medulla,  and  it  will  be  seen 
that  in  the  cervical  region  the  degen- 
erated fibers  are  grouped  in  the  area  of 
the  fasciculus  gracilis  (see  Fig.  77).  The 


SPINAL    CORD    AS    A    PATH    OF    CONDUCTION.  171 

endogenous  fibers,  so  far  as  they  are  ascending,  represent  afferent 
paths  in  which  two  or  more  neurons  are  concerned.  The  pos- 
terior root  fibers  concerned  in  these  paths  end  in  the  gray  matter 
of  the  cord,  and  thence  the  conduction  is  continued  by  one  or 
more  tract  cells.  The  conduction  by  this  set  of  fibers  may  be  on 
the  same  side  of  the  cord  as  that  on  which  the  root  fibers  entered ; 
or  it  may  be  crossed,  or,  using  a  convenient  terminology,  it  may 
be  homolateral  or  contralateral.  The  endogenous  fibers  are  not 
a  conspicuous  feature  of  the  posterior  funiculi  and  little  is  known 
of  their  physiological  significance.  The  physiological  value  of 
the  exogenous  or  root  fibers  in  the  posterior  funiculi  has  been  in- 
vestigated by  a  large  number  of  observers.  The  physiologists  have 
employed  the  direct  method  of  cutting  the  funiculi  in  the  thoracic  or 
lumbar  region  and  observing  the  effect  upon  the  sensations  of  the 
parts  below  the  lesion.  The  positive  results  of  these  experiments 
have  been  difficult  to  define.  Most  of  the  older  observers  found 
that  there  was  no  detectable  change  in  the  sensations  of  the  parts 
below,  but  they  paid  attention  only  to  cutaneous  sensations,  and, 
indeed,  chiefly  to  the  sense  of  pain.  Later  observers*  have  differed 
also  in  their  description  of  the  effects  of  this  operation;  but 
most  of  them  state  that  the  animal  shows  an  awkwardness  or 
lack  of  skill  in  the  movements  of  the  hind  limbs,  especially  in 
the  finer  movements,  and  this  effect  is  interpreted  to  mean  that 
there  is  some  loss  of  muscle  sense.  This  conclusion  is  strength- 
ened by  the  results  of  pathological  anatomy.  In  the  disease 
known  as  tabes  dorsalis  the  posterior  funiculi  of  the  cord  in  the 
lumbar  region  are  affected  and  the  striking  symptom  of  this 
condition  is  an  interference  with  the  power  of  co-ordinating 
properly  the  movements  of  the  lower  limbs,  particularly  in  the 
act  of  maintaining  body  equilibrium  in  standing  and  walking, — 
a  condition  known  as  locomotor  ataxia.  So  far  as  the  cutaneous 
sensations  are  concerned, — that  is,  the  sensations  of  touch 
(pressure),  pain,  and  temperature, — all  observers  agree  that  the 
two  latter  are  not  affected  by  section  of  the  funiculi,  while  regarding 
touch,  opinions  have  differed  radically.  Schiff  contended  that 
touch  sensations  are  detectable  as  long  as  these  funiculi  are  intact, 
and  are  seriously  interfered  with  when  they  are  sectioned;  but  most 
of  the  results,  pathological  and  experimental,  indicate  that  when 
the  continuity  of  these  fibers  is  destroyed,  the  sense  of  touch  is 
still  present  in  the  parts  supplied  by  the  cord  below  the  lesion. 
An  explanation  of  the  confusion  in  the  reported  results  may  be 
found  perhaps  in  the  fact  reported  below  (see  p.  175)  that  fibers 
conveying  the  impulses  necessary  to  tactile  discrimination  pass 
upward  in  these  funiculi,  while  other  touch  (pressure)  impulses 

*Borchert,  "Archiv  f.  Physiologic,"  1902,  389.     See  also  Sherrington, 
"Journal  of  Physiology,"  14,  255,  1893. 


172 


PHYSIOLOGY    OF    CENTRAL    NEKVOUS    SYSTEM. 


cross  in  the  cord  and  pass  upward  in  the  anterior  funiculi.  To 
summarize,  therefore,  we  may  say  that  the  evidence  at  hand 
proves  that  the  ascending  fibers  of  the  posterior  funiculi  do  not 
convey  impulses  of  pain  or  temperature,  that  if  they  convey 
any  cutaneous  touch  (pressure)  impulses,  they  certainly  do  not 
form  the  only  path  of  conduction  for  this  sense,  and  that  most 
probably  their  chief  function  is  the  conduction  of  impulses  of  muscle 
sense, — that  is,  they  consist  of  those  deep  sensory  fibers  from  the 
voluntary  muscles,  the  tendons,  and  the  joints,  through  which  we 
obtain  an  idea  of  the  position  of  the  limbs  and  the  state  of  con- 
traction of  the  muscles.  The  sensations  thus  aroused  in  the  higher 
parts  of  the  brain  are  necessary  to  the  proper  co-ordination  of  the 
movements  of  the  muscles.  Injury  to  these  funiculi,  therefore, 
while  it  does  not  cause  paralysis,  is  followed  by  disorderly — that 
is,  ataxic — movements.  On  the  histological  side  it  has  been  shown, 
as  stated  above,  that  these  fibers  end  in  nuclei  of  the  medulla, 
and  thence  are  continued  forward  by  the  great  sensory  tract 
known  as  the  "lemniscus,"  to  end  eventually  in  that  part  of  the 
cortex  of  the  cerebrum  designated  as  the  area  of  the  body  senses. 
Ascending  (Afferent  or  Sensory)  Paths  in  the  Lateral  Funiculi. — 
The  two  best  known  ascending  tracts  in  these  funiculi  are  those  of 
the  cerebellospinal  and  the  superficial  anterolateral  fasciculi.  Both 
of  these  tracts  are  composed  of  endogenous  fibers.  The  former 
takes  its  origin  in  the  lower  thoracic  region,  and  is  composed  of 

axons  connected  with  the  tract 
cells  of  the  dorsal  nucleus.  The 
impulses  which  its  fibers  con- 
vey are  brought  into  the  cord 
through  those  fibers  of  the 
posterior  root  that  end  around 
the  cells  of  the  dorsal  nu- 
cleus. A  number  of  the  fibers 
in  this  funiculus  end  doubt- 
less in  the  gray  matter  of 
the  upper  regions  of  the  cord, 
but  most  of  them  continue 
upward  on  the  same  side, 
enter  the  inferior  peduncle  of 
the  cerebellum  (restiform 
body),  and  terminate  in  the 
posterior  and  median  portions 

of  the  vermiform  lobe,  mainly  on  the  same  side,  but  partly  also  on 
the  opposite  side.  The  superficial  anterolateral  fasciculus,  situ- 
ated ventrally  to  the  cerebellospinal  fasciculus  (gr,  Fig.  75), 
may  extend  forward  into  the  anterior  funiculi  along  the  periphery 
of  the  cord.  The  two  bundles  may  be  more  or  less  intermingled 


a.c 


Fig.  78. — To  show  the  course  of  the  fibers 
of  the  cerebellar  tracts  of  the  cord  (Molt): 
v.a.c..  Ventral  tract  (superficial  anterolateral); 
d.a.c.,  dorsal  tract  (cerebellospinal);  s.v., 
superior  vermis;  P.C.Q.,  inferior  colliculus. 


SPINAL    CORD    AS    A    PATH    OF    CONDUCTION.  173 

at  the  points  of  contact.  This  tract  begins  in  the  lumbar  region,  its 
fibers  arising  on  the  same  side  from  tract  cells  situated  in  the  inter- 
mediate portions  of  the  gray  matter,  or,  according  to  Bruce,*  in  the 
lower  cells  of  the  column  of  Clarke.  This  author  states  also  that 
fibers  belonging  to  this  tract  in  the  lower  thoracic  region  may  pass 
over  into  the  tract  of  Flechsig  at  higher  levels.  Many  of  the  fibers  in 
this  tract  possibly  terminate  in  the  cord  itself,  since  the  bundle  does 
not  increase  regularly  in  size  as  it  passes  up  the  cord.  Most  of  the 
bundle  continues  forward,  however,  along  the  ventral  side  of  the 
pons,  gradually  shifts  more  to  the  dorsal  side,  and  at  the  level  of  the 
superior  peduncles  of  the  cerebellum  turns  backward,  for  the  most 
part,  at  least,  and  passes  to  the  cerebellum  by  way  of  the  superior 
peduncle  (brachium  conjunct ivum)  and  the  anterior  medullary 
velum,  to  end  in  the  vermiform  lobe  chiefly  on  the  same  side,  but  to 
some  extent  on  the  opposite  sidef  (Fig.  78).  The  area  of  dis- 
tribution of  these  fibers  lies  anterior  or  headward  of  those  arising 
in  the  dorsal  cerebellospinal  tract  (Flechsig).  Where  this  tract 
separates  from  the  cerebellospinal  fasciculus  it  is  stated  t  that  it 
gives  off  a  number  of  fibers  which  enter  the  restiform  body  with 
the  cerebellospinal  fasciculus  to  end  in  the  cerebellum.  This 
and  other  facts  indicate  that  the  two  tracts  constitute  a  com- 
mon system.  Regarding  the  physiology  of  these  two  tracts 
there  is  little  experimental  and  not  much  clinical  evidence. 
Some  observers  have  cut  the  cerebellospinal  fasciculus  in  ani- 
mals, but  with  no  very  obvious  effect  except  again  a  slight 
degree  of  ataxia  in  the  movements  below  the  lesion  and  some 
loss  of  muscular  tone.§  This  result,  together  with  the  fact 
that  the  bundle  ends  in  the  cerebellum,  gives  reason  for  be- 
lieving that  the  fibers  convey  afferent  impulses  from  the  muscles. 
As  we  shall  see,  much  evidence  of  various  kinds  connects  the  cere- 
bellum with  the  co-ordination  of  the  muscles  of  the  body  in  the 
complex  movements  of  standing  and  locomotion.  This  power 
of  co-ordination  in  turn  depends  upon  the  afferent  impulses 
from  the  muscles  and  the  joints  and  other  so-called  deep  sen- 
sory parts,  and  since  the  fibers  of  the  cerebellospinal  fasciculus 
end  in  the  cerebellum,  and  since  experimental  lesion  of  them 
gives  no  loss  of  cutaneous  sensibility,  but  some  degree  of  ataxia, 
it  seems  justifiable  to  conclude  that  these  fibers  are  physiolog- 
ically muscle-sense  fibers.  The  similar  fibers  in  the  posterior 
funiculi  end  eventually  in  the  cortex  of  the  cerebrum,  and  may 
be  supposed,  therefore,  to  mediate  our  conscious  muscular  sensa- 

*  Bruce,  "Quarterly  Journal  of  Exp.  Physiology,"  3,  391,  1910. 

t  For  the  literature  upon  these  tracts  see  Van  Gehuchten,  "Le  NeVraxe," 
3,  157,  1901;  Horsley  and  Macnalty,  "Brain,"  1909,  237,  and  Bruce,  loc.  cit. 

tSchafer  and  Bruce,  "Journal  of  Physiology,"  1907  ("Proc.  Physiol. 
Soc."). 

§Bing,  "ArchivfUr  Physiologic,"  1906,  250;  also  Horsley  and  Macnalty, 
loc.  cit. 


174  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

tions,  but  these  fibers  in  the  cerebellospinal  tract  end  in  the  cere- 
bellum, an  organ  which,  so  far  as  we  know,  gives  rise  to  no  con- 
scious sensations.  To  speak  of  them,  therefore,  as  muscle-sense 
fibers  may  be  somewhat  misleading,  and  it  may  be  better  to  follow 
the  plan  of  designating  them  as  the  non-sensory  afferent  fibers 
arising  from  tissues  beneath  the  skin,  such  as  the  muscles,  the 
tendons,  and  the  ligaments  round  the  joints.  The  superfi- 
cial anterolateral  fasciculus  has  been  the  subject  of  some  ex- 
perimental study  from  the  physiological  side,  but  the  results 
have  been  negative.  Clinically,  the  tract  may  be  involved 
in  pathological  or  traumatic  lesions  of  the  lateral  funiculi.  Gow- 
ers*  gives  a  history  of  some  such  cases,  which  lead  him  to  be- 
lieve that  this  tract  constitutes  a  pathway  for  pain  impulses, 
and  this  view  or  the  view  that  it  conducts  the  impulses  of  both  pain 
and  temperature  has  been  more  or  less  generally  accepted.  Entire 
confidence,  however,  cannot  be  placed  in  this  conclusion,  since  the 
lesions  in  question  were  not  strictly  confined  to  the  fasciculus 
in  question,  although  clinical  evidence  indicates  that  the  fibers 
conveying  impulses  of  pain  or  of  pain  and  temperature  lie  in  the 
ground  bundles  in  the  neighborhood  of  this  tract.  The  only  posi- 
tive indication  that  we  have  concerning  the  physiological  value  of 
this  specific  tract  of  fibers  is  given  by  their  histology  in  the  fact  that 
they  end,  for  the  most  part,  in  the  cerebellum.  The  cerebellum, 
we  know,  may  be  removed  in  dogs  and  monkeys  without  loss  of  the 
sensation  of  pain,  temperature,  or  touch,  and  this  fact  speaks 
strongly  against  the  view  that  either  the  cerebellospinal  or  the 
superficial  anterolateral  fasciculus  is  concerned  in  the  conduction  of 
these  cutaneous  sensations.  From  a  physiological  standpoint  we 
should  be  inclined  to  believe  that  both  of  these  tracts  conduct  non- 
sensory  afferent  impulses  from  the  tissues  lying  under  the  skin, 
particularly  from  the  muscles,  tendons,  and  joints.  It  would  seem, 
therefore,  that  all  the  long  ascending  tracts  in  the  posterior  and 
lateral  funiculi  of  the  cord  may  be  made  up  of  fibers  of  muscular 
sensibility,  using  this  term  in  a  wise  sense  to  include  the  deep 
sensibility  of  the  joints,  tendons,  and  muscles.  The  immense 
importance  of  muscular  control  in  the  maintenance  of  life  and  in 
defense  against  enemies  may  explain,  upon  the  doctrine  of  the 
struggle  for  existence,  why  the  long  paths  should  have  been  devel- 
oped first  in  connection  with  this  sense. 

The  Spinal  Paths  for  the  Cutaneous  Senses  (Touch,  Pain, 
and  Temperature). — From  the  facts  stated  in  the  last  two  para- 
graphs it  would  seem  probable  that  the  spinal  paths  for  touch, 
pain,  and  temperature  must  be  along  the  short  association 
tracts  of  the  proper  fasciculi  of  the  lateral  and  anterior  funiculi. 
There  is  evidence  from  the  clinical  side  that  the  paths  of  con- 
*  Cowers,  "Lancet,"  1886. 


SPINAL    CORD    AS    A    PATH    OF    CONDUCTION.  175 

duction  for  these  senses  are  separate.  In  the  pathological 
condition  known  as  syringomyelia,  cavities  are  formed  in  the 
cord  affecting  chiefly  the  central  gray  matter  and  the  contiguous 
portions  of  the  white.  In  these  cases  a  frequent  symptom  is 
what  is  known  as  the  dissociation  of  sensations;  the  patient 
loses,  in  certain  regions,  the  sensations  of  pain  and  temperature 
(analgesia  and  thermo-anesthesia),  but  preserves  that  of  pressure 
(touch).  Facts  of  this  kind  indicate  that  the  paths  of  conduc- 
tion for  touch  are  separate  from  those  for  pain  and  temperature, 
but  little  that  is  positive  is  known  regarding  the  exact  location  of 
these  paths.  The  fibers  of  pain  and  temperature  probably  end 
in  the  gray  matter  of  the  cord  (posterior  column)  soon  after  their 
entrance,  and  the  path  is  continued  upward  by  tract  cells  whose 
axons  enter  the  proper  fasciculi  in  the  anterolateral  funicuh,* 
but  the  number  of  such  neurons  concerned  in  the  conduction  as  far 
as  the  medulla  is  not  known.  Regarding  the  path  for  the  touch 
impulses  a  singular  amount  of  uncertainty  has  prevailed.  This 
sense  is  not  lost  or,  at  least,  is  rarely  lost  in  cases  of  syringomyelia 
in  which  the  other  cutaneous  senses  are  affected.  On  the  other 
hand,  the  posterior  funiculi,  as  we  have  seen,  may  be  completely 
sectioned  in  lower  animals  without  destroying  the  sense  of  touch 
and  in  the  case  of  man  extensive  pathological  lesions  of  the  same 
funiculi  are  reported  in  which  the  sense  of  touch  was  not  lost. 
Some  authors,  therefore,  have  been  led  to  believe  that  the  touch 
impulses  may  be  conveyed  up  the  cord  by  several  paths:  by  the 
long  association  fibers  of  the  posterior  funiculi,  and  by  the  short 
association  fibers  of  the  lateral  funiculi.  Such  a  view  receives 
little  support  from  the  experimental  work  on  the  lower  mammals. 
In  these  animals  the  evidence  tends  to  show  that  the  conduction 
is  by  way  of  the  lateral  or  anterolateral  funiculi,  by  means  of  tract 
cells  and  short  association  tracts.  The  fact  that  in  man  the 
clinical  evidence  seems  to  point  to  the  posterior  funiculi  as  a  pos- 
sible or,  indeed,  probable  path  for  these  fibers  may  serve  to  ex- 
emplify the  fact  that  in  these  matters  the  various  mammalia 
differ  more  or  less  according  to  the  degree  of  their  development. 
It  seems  possible  that,  so  far  as  man  is  concerned,  an  explanation 
of  the  difference  of  opinion  regarding  the  spinal  paths  of  the  sense 
of  touch  is  found  in  the  distinction  made  by  Head  and  Thompson  f 
between  tactile  discrimination  and  cutaneous  sensibility  to  touch. 
By  the  former  is  meant  the  ability  to  discriminate  between  two 
stimuli  applied  simultaneously  to  the  skin  at  a  certain  distance 
apart,  by  the  latter,  the  ability  to  perceive  and  locate  accurately 
a  light  pressure  stimulus  applied  to  the  skin.  These  two  forms  of 

*  For  discussion,  see  Bertholet,  "Le  Nevraxe,"  1906,  vii.,  283,  for  the 
lower  animals;  Head  and  Thompson,  "Brain,"  1906,  p.  537,  and  Thompson, 
"Lancet,"  1909,  for  man. 

t  Head  and  Thompson,  "Brain,"  1906;  also  Saunders,  "Brain,"  36, 166, 1913. 


176  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

cutaneous  touch  sensations  are  mediated  according  to  these  authors 
by  separate  systems  of  fibers.  As  the  result  of  a  spinal  lesion  the 
power  of  discrimination  may  be  lost  over  a  given  area  of  skin 
which  otherwise  is  completely  sensitive  to  all  cutaneous  stimuli. 
They  find  that  the  fibers  of  tactile  discrimination  travel  up  the 
cord  uncrossed  in  the  posterior  funiculi,  together  with  the  fibers 
of  muscle  sense — that  is,  the  fibers  which  give  us  a  sense  of  posi- 
tion and  movement  of  the  limbs.  The  fibers  of  cutaneous  touch 
sensations  in  general,  on  the  contrary,  cross  to  the  other  side  be- 
fore reaching  the  medulla,  and  pass  upward  in  the  anterolateral 
ground-bundles. 

Homolateral  and  Contralateral  Conduction  of  the  Cutaneous 
Impulses. — Great  interest,  from  the  medical  side,  has  been  shown 
in  the  question  of  the  crossed  or  uncrossed  conduction  of  the 
cutaneous  impulses  in  the  cord.  The  matter  is  naturally  one 
of  importance  in  diagnosis.  In  human  beings  it  was  pointed 
out  by  Brown-Sequard*  that  unilateral  lesions  of  the  cord  are 
followed  by  muscular  paralysis  below  on  the  same  side,  and  loss 
of  cutaneous  sensibility  on  the  opposite  side.  This  syndrome 
has  been  held  clinically  to  establish  the  diagnosis  of  a  unilateral 
lesion,  and  has  led  to  the  view  that,  while  the  conduction  of 
motor  impulses  in  the  cord  is  homolateral,  that  of  the  cutaneous 
sensory  impulses  is  contralateral.  Experimental  work  on  lower 
animals,  on  the  contrary,  has  not  supported  this  view.  While 
results  in  this  direction  have  varied,  as  would  be  expected  from 
the  intrinsic  difficulties  connected  with  the  interpretation  of 
the  sensations  of  an  animal,  the  general  outcome  has  been  to 
show  that  the  sensory  conduction  is  bilateral,  but  mainly  on 
the  same  side.  That  is,  if  the  cord  is  cut  on  one  side  only  (hemi- 
sected)  in  the  thoracic  region,  the  cutaneous  sensibility  of  the  parts 
below  the  lesion  is  impaired  upon  the  same  side,  but  not  com- 
pletely abolished,  showing  that  some  crossing  has  taken  place,  f 
In  fact,  it  is  stated  that  pain  sensations  in  the  lower  animals  are 
not  abolished  by  a  double  hemisection,  {  that  is  to  say,  by  a  hemi- 
section  below,  in  the  thoracic  cord  for  example,  on  one  side,  and  a 
hemisection  above,  cervical  cord,  on  the  other  side.  That  the 
pain  impulses  get  through  to  the  brain  under  this  condition  would 
seem  to  imply  that  they  are  conveyed  either  diffusely  through  the 
central  gray  matter,  or  that  they  cross  a  number  of  times  from  one 
side  to  the  other.  In  man  the  evidence  from  the  clinical  side,  as 
far  as  it  goes,  indicates  that  the  paths  for  touch,  pain,  and  tempera- 
ture are  more  specialized  than  in  the  lower  mammals,  so  that  the 
results  obtained  from  experiments  upon  the  latter  must  be  used 

*  Brown-Sequard,  "Journal  de  Physiologic,"  6,  124,  232,  581,  1863. 
t  Mott,  "Brain,"  1895,  1,  and  Bertholet,  "Le  Nevraxe,"  1906,  vii.,  283. 
t  Karplus  and  Kreidl,  "Pfluger's  Archiv,"  158,  275,  1914. 


SPINAL    CORD    AS    A    PATH    OF    CONDUCTION. 


177 


with  caution  in  the  diagnosis  of  human  lesions.  Head  and  Thomp- 
son, in  the  paper  previously  referred  to,  conclude,  upon  the  basis  of 
extensive  clinical  studies,  that  in  man  all  the  fibers  of  cutaneous 
sense  cross  in  the  cord  except  those  mediating  tactile  discrimination. 
As  stated  above,  these  latter  pass  upward  in  the  posterior  funiculi 
together  with  some  of  the  fibers  of  muscle  sense,  and  do  not  cross 


Fig.  79. — Diagram  of  the  afferent  nerve-fibers  and  their  course  in  the  spinal  cord:  a,  Specific 
receptor  for  painful  impulses;  b,  specific  receptor  for  heat  impulses;  c,  specific  receptor  for  cold 
impulses;  d,  specific  receptor  for  tactile  impulses;  e,  specific  receptor  for  impulses  of  passive 
position  and  tactile  discrimination;  /,  specific  receptor  for  non-sensory  afferent  impulses;  1, 
sensory  fibers  of  the  second  order  for  pain,  heat,  and  cold;  2,  sensory  fibers  of  the  second  order 
for  touch;  3,  sensory  fibers  of  the  second  order  for  passive  position  and  tactile  discrimination; 
4,  long  fibers  (uncrossed)  in  the  P9sterior  column  of  the  cord;  5,  spinocerebellar  tracts  (lateral 
columns)  for  non-sensory  afferent  impulses  (from  Thompson,  slightly  modified). 

until  after  they  reach  the  medulla.  These  authors  in  studying  the 
sensory  paths  in  the  spinal  cord  make  a  distinction,  in  the  first  place, 
between  cutaneous  sensibility  and  deep  sensibility.  By  the  latter 
term  they  designate  the  senses  of  pressure,  of  pain,  and  of  position 
resident  in  the  muscles,  tendons,  and  other  parts  beneath  the  skin. 
Cutaneous  sensibility  they  divide  further  into  epicritic  sensibility 
12 


178 


PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 


(touch,  cold,  heat)  and  protopathic  sensibility  (cold,  heat,  pain), 
see  p.  278.  The  fibers  of  these  three  general  varieties  are  regrouped 
in  the  cord  in  such  a  way  that  the  epicritic  and  protopathic 
temperature  fibers  are  brought  together  into  a  common  tract, 
which  is  contralateral;  the  deep  and  cutaneous  pain  fibers  are 
likewise  united  into  a  common  tract,  which  is  contralateral,  and 
cutaneous  pressure  fibers,  except  those  mediating  tactile  discrim- 
ination, unite  with  the  deep  pressure  fibers  to  form  a  common  tract 
which  crosses  the  mid-line  less  promptly.  This  conception  is 
indicated  in  the  accompanying  schema  (Fig.  79).  According 
to  their  interpretation,  a  complete  unilateral  lesion  of  the 

cord  in  the  cervical  region  would 
be  followed  by  a  homolateral 
loss  of  motion  in  the  parts  below, 
and  also  of  tactile  discrimination 
and  muscle  sense,  using  the  latter 
term  to  cover  the  deep  sensibility  in 
regard  to  position  and  movements 
of  the  limbs.  On  the  contralateral 
side  there  would  be  a  loss  of  pain, 
temperature,  and  pressure. 

The  Descending  (Efferent  or 
Motor)  Paths  in  the  Antero-lateral 
Funiculi. — The  main  descending 
path  in  the  cord  is  the  pyramidal 
or  cerebrospinal  system  of  fibers. 
In  mant  as  shown  in  Fig.  75,  there 
are  two  fasciculi  belonging  to  this 
system — the  anterior  and  the  lat- 
eral pyramidal  tracts.  Both  tracts 
arise  from  the  anterior  pyramids  on. 
the  ventral  face  of  the  medulla, 
whence  the  name  of  the  pyramidal 
system.  At  the  junction  of  the 
medulla  and  cord  the  fibers  of  the 
pyramids  decussate  in  part,  form- 
ing a  conspicuous  feature  of  the 
internal  structure  at  this  point, 
known  as  the  pyramidal  decussa- 
tion.  According  to  the  general 
schema  of  this  decussation  (see  Fig. 
80),  the  larger  number  of  the  fibers 
in  the  pyramid  of  one  side  pass 
over  to  form  the  lateral  pyramidal 
fasciculus  of  the  other  side  of  the  cord  (4,  5),  while  a  smaller  part 
(3)  continues  down  on  the  same  side  to  form  the  anterior  pyra- 


Fig.  80. — Schema  representing 
the  course  of  the  fibers  of  the  pyra- 
midal or  cerebrospinal  system:  1, 
Fibers  to  the  nuclei  of  the  cranial 
nerve;  2,  uncrossed  fibers  to  the 
lateral  pyramidal  fasciculus;  3,  fibers 
to  the  anterior  pyramidal  fasciculus 
crossing  in  the  cord;  4  and  5,  fibers 
that  cross  in  the  pyramidal  decussa- 
tion to  make  the  lateral  pyramidal 
fasciculus  of  the  opposite  side. 


SPINAL    CORD    AS    A    PATH    OF    CONDUCTION.  179 

midal  fasciculus.  Eventually,  however,  these  latter  fibers  also 
cross  the  mid-line  in  the  anterior  white  commissure,  not,  however, 
all  at  once,  as  at  the  pyramidal  decussation,  but  some  at  the  level 
of  each  spinal  nerve.  These  pyramidal  fibers  have  their  origin 
in  large  pyramidal  cells  (Betz  cells)  lying  in  the  cortex  of  the  ante- 
rior central  convolution  of  the  cerebrum;  some  of  them  cross 
the  mid-line  before  reaching  the  medulla  to  end  around  the  cells 
of  origin  of  the  cranial  nerves,  but  the  greater  number  continue 
into  the  cord  and,  after  crossing  the  mid-line  in  the  pyramidal 
decussation  or  in  the  anterior  white  commissure,  terminate 
around  the  motor  cells  of  the  anterior  columns  which  give  rise 
to  the  motor  roots  of  the  spinal  nerves.  Both  fasciculi,  the 
lateral  and  the  anterior,  continue  throughout  the  length  of  the 
cord,  diminishing  in  area  on  the  way  as  some  of  their  fibers  ter- 
minate in  each  segment.  This  system  of  fibers  is  supposed  to 
represent  the  mechanism  for  effecting  voluntary  movements, 
and  according  to  the  general  schema  the  voluntary  motor  path 
from  cerebrum  to  muscle  comprises  two  neurons, — the  pyra- 
midal or  cerebrospinal  neuron  and  the  spinal  or  the  cranial 
neuron.  Moreover,  as  represented  in  the  schema,  the  innerva- 
tion  is  crossed,  the  right  side  of  the  brain  controlling  the  mus- 
culature of  the  left  side  of  the  body  and  vice  versa.  As  we  shall 
see,  however,  when  we  come  to  study  the  motor  areas  of  the 
brain,  this  rule  has  important  exceptions,  and  histologically 
there  is  proof  that  some  of  the  fibers  in  each  pyramid  (2  in 
Fig.  80).  continue  into  and  terminate  in  the  cord  on  the  same 
side.  The  pyramidal  system  varies,  among  the  different  verte- 
brates, in  an  interesting  way,  in  the  extent  of  its  development  and 
in  its  location  in  the  cord.*  It  reaches  its  highest  development  in 
man  and  the  anthropoid  apes.  In  the  other  mammalia  it  is  rela- 
tively less  important  and  the  anterior  fasciculus  may  be  lacking 
altogether.  In  the  birds  what  represents  the  same  system  is 
found  in  the  anterior  funiculus  (Sandmeyer),  while  in  the  frog 
the  system  does  not  exist  at  all. 

The  relative  importance  of  the  system  in  the  different  mammalia 
is  indicated  in  the  accompanying  table,  taken  from  Lenhossek,f 
in  which  the  area  of  the  pyramidal  system  is  given  in  percentage 
of  the  total  cross-area  of  the  cord: 

Mouse 1.14  per  cent. 

Guinea  pig 3.0 

Rabbit.. 5.3 

Cat 7.76 

Man 11.87 

Evidently,    therefore,    the   importance   of   the   pyramidal   system 

*  Simpson,  "Quarterly  Journal  of  Exp.  Physiology,"  8,  79,  1914. 
t  Lenhossek,  "Bau  des  Nervensystems,"  second  edition,  1895. 


180  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

varies  in  different  animals,  and  it  is  necessary  to  bear  this  fact 
in  mind  in  applying  the  results  of  experiments  on  the  lower  animals 
to  man.  In  the  lowest  vertebrates  there  are  undoubtedly  motor 
paths  between  the  brain  and  cord  through  which  so-called  voluntary 
movements  are  effected,  but  these  are  probably  short  paths  in- 
volving a  number  of  neurons.  The  higher  the  position  of  the 
animal  in  the  phylogenetic  scale,  the  more  complete  is  the  develop- 
ment of  the  long  pyramidal  system;  but  even  in  the  higher  mam- 
mals it  is  probable  that  motor  paths,  other  than  the  pyramidal 
system,  connect  the  cortex  and  subcortical  centers  with  the  motor 
nuclei  in  the  cord.  In  the  dog,  for  example,  section  of  the  pyramids 
is  not  followed  by  complete  paralysis,  and,  indeed,  after  such  sections 
stimulation  of  the  motor  areas  of  the  cortex  still  causes  definite  mus- 
cular movements.*  One  such  indirect  motor  path  is  referred  to  be- 
low in  connection  with  the  rubrospinal  tract  (Monakow's  bundle) . 

Less  Well-Known  Tracts  in  the  Cord. — In  addition  to  the 
tracts  just  described  there  are  a  number  of  others — mainly,  descend- 
ing tracts — concerning  which  our  anatomical  knowledge  is  less 
complete,  and  the  physiological  value  of  which  is  entirely  un- 
known or  at  best  is  a  matter  of  inference  from  the  anatomical 
relations,  f 

Descending  Tracts  in  the  Posterior  Funiculus — Comma  Tract; 
Oval  Field. — In  the  posterior  funiculi  several  tracts  of  descending 
fibers  have  been  described.  The  comma  tract  of  Schultze  is 
found  in  the  cervical  and  the  upper  thoracic  cord.  The  bundle 
lies  at  the  border-line  between  the  fasciculus  gracilis  and  the 
fasciculus  cuneatus.  In  the  lower  regions  of  the  cord,  lumbar 
and  sacral,  similar  small  areas  of  descending  fibers  are  found — 
oval  field  (Flechsig),  median  triangle  (Gombault  and  Philippe) — 
which  represent  possibly  different  systems.  These  fibers  have  been 
explained  as  descending  association  tracts  connecting  distant  parts 
of  the  gray  matter  of  the  cord,  but  recent  workj  indicates  that 
they  may  represent  simply  the  descending  limb  of  entering  poste- 
rior root  fibers.  When  the  latter  enter  the  cord  they  divide  in  T, 
one  branch  passing  upward,  the  other  downward  for  a  short  dis- 
tance. On  this  interpretation  the  fibers  in  question  do  not  consti- 
tute a  descending  tract,  physiologically  speaking,  in  spite  of  their 
descending  degeneration. 

Descending  Tracts  in  the  Anterolateral  Funiculus. — The  pre- 
pyramidal  tract,  known  also  as  Monakow's  bundle,  the  fasciculus 
intermediolateralis,  or  the  rubrospinal  tract,  is  a  conspicuous 

*Rothmann,  "Zeitschrift  f.  klin.  Med.,"  vol.  xlviii.,  1903;  Schafer, 
"Quarterly  Journal  of  Exp.  Physiology,"  3,  355,  1910. 

t  Collier  and  Buzzard,  "Brain,"  1901,  177;  Fraser,  "Journal  of  Physi- 
ology," 28,  366,  1902.  For  summary  and  literature  consult  Van  Gehuchten, 
"Anatomic  du  systeme  nerveux  de  rhomme." 

t  "Brain,"  vol.  xxxvi.,  1913. 


SPINAL    CORD    AS    A    PATH    OF    CONDUCTION.  181 

bundle  forming  a  wedge-shaped  or  triangular  area  in  the  lateral 
columns  between  the  lateral  pyramidal  fasciculus  and  the 
superficial  anterolateral  fasciculus  (Gower's),  or,  perhaps,  more 
correctly  speaking,  forming  the  anterior  portion  of  the  lateral 
pyramidal  fasciculus;  the  two  systems  being  more  or  less  inter- 
mingled. The  fibers  composing  this  bundle  are  descending 
fibers  that  take  their  origin  in  the  midbrain  in  the  cells  of  the 
red  nucleus.  Shortly  after  their  origin  they  cross  to  the  opposite 
side  and,  passing  through  the  pons  and  medulla,  enter  the  spinal 
cord  in  the  lateral  funiculi,  in  which  they  may  be  detected  as  far 
as  the  sacral  region.  These  fibers  terminate  around  cells  lying  in 
the  posterior  part  of  the  anterior  column  of  gray  matter,  whose 
axons,  in  turn,  probably  emerge  through  the  anterior  roots.  This 
tract,  therefore,  constitutes  a  crossed  motor  path  from  midbrain 
to  the  anterior  roots,  and,  since  the  red  nucleus,  in  turn,  is  con- 
nected with  the  cerebrum,  either  directly  or  by  way  of  the  cere- 
bellum, it  represents  a  cerebrospinal  motor  path  in  addition 
to  that  offered  by  the  pyramidal  system. 

The  vestibulospinal  fibers  lie  anterior  to  the  preceding  tract 
in  the  anterolateral  funiculus;  they  may  extend  into  the  anterior 
funiculus  as  far  as  the  anterior  pyramidal  fasciculus.  It  is  stated 
that  they  arise  in  cells  of  the  nucleus  of  Deiters  and  the  nucleus  of 
Bechterew,  and  similar  cells  lying  in  the  region  of  the  pons.  In 
the  cord  these  fibers  end  around  cells  in  the  anterior  column. 
Since  the  Deiters  nucleus  forms  a  termination  for  the  sensory 
fibers  of  the  vestibular  branch  of  the  eighth  cranial  nerve,  and  since 
these  fibers  are  believed  to  give  us  a  sense  of  the  position  of  the  body 
and  to  be  concerned  in  the  reflex  adjustment  of  the  muscles  in  the 
movements  used  to  maintain  equilibrium,  their  connection  in 
Deiters'  nucleus  with  a  spinal  motor  path  becomes  very  significant 
as  furnishing  a  reflex  arc  through  which  sensory  impressions  from 
the  vestibular  apparatus  in  the  ear  may  automatically  control 
the  musculature  of  the  body.  A  number  of  other  descending 
paths  in  the  anterior  and  lateral  funiculi  have  been  described, 
such  as  Helweg's  bundle  or  the  olivospinal  tract,  lying  on  the 
margin  of  the  cord  at  the  junction  of  the  anterior  and  the  lateral 
funiculi  and  supposed  to  arise  in  the  olivary  bodies;  the  anterior 
and  the  lateral  reticulospinal  tracts  arising  from  cells  in  the 
reticular  formation  of  medulla,  pons,  and  midbrain;  and  the 
continuation  into  the  cord  of  the  important  medial  longitudinal 
fasciculus  (post.  long,  bundle),  which  extends  from  the  midbrain 
through  to  the  cord  and  connects  the  motor  nuclei  of  the  cranial 
nerves  with  the  motor  centers  of  the  cord.  Concerning  these 
and  similar  tracts  our  physiological  knowledge  is  scanty,  and  it 
is  not  possible  at  present  to  employ  them  with  certainty  in 
explaining  the  activity  of  the  neuromuscular  apparatus. 


CHAPTER  IX. 

THE  GENERAL  PHYSIOLOGY  OF  THE  CEREBRUM 
AND  ITS  MOTOR  FUNCTIONS. 

From  the  time  of  Galen  in  the  second  century  of  the  Christian 
era  the  cerebrum  has  been  recognized  as  the  organ  of  intelligence 
and  conscious  sensations.  Galen  established  this  view  not  only  by 
anatomical  dissections,  confirming  the  older  work  of  the  Alexandrian 
school  (third  century  B.C.)  in  regard  to  the  origin  from  the  brain 
of  the  cranial  nerves,  but  also  by  numerous  vivisection  experiments 
upon  lower  animals.  All  modern  work  has  confirmed  this  belief 
and  has  tended  to  show  that  in  the  cerebral  hemispheres  and,  indeed, 
in  the  cortex  of  gray  matter  lies  the  seat  of  consciousness. 
It  is  perhaps  still  an  open  question  as  to  the  existence  of  a 
conscious  or  psychical  factor  in  the  activities  of  other  parts  of  the 
nervous  system,  but  there  is  no  doubt  that  the  highest  develop- 
ment of  psychical  activity  in  man  is  associated  with  the  cortical  mat- 
ter of  the  cerebrum.  In  the  young  infant  the  dawn  of  its  mental 
powers  is  connected  with  and  dependent  on  the  development  of  the 
normal  cortical  structure,  while  in  extreme  age  the  failure  in  the 
mental  faculties  goes  hand  in  hand  with  an  atrophy  of  the  elements 
of  the  cortex.  If  this  cortex  were  removed  all  the  intelligence,  sen- 
sation, and  thought  that  we  recognize  as  characterizing  the  highest 
psychical  life  of  man  would  be  destroyed,  and  abnormalities  hi  the 
structure  of  this  cortical  material  are  accepted  as  the  probable 
causal  factor  of  those  perversions  in  reasoning  and  in  character 
which  are  exhibited  by  the  insane  or  the  degenerate.  The  cortical 
gray  matter,  therefore,  is  the  chief  organ  of  the  psychical  life,  the 
tissue  through  whose  activity  the  objective  changes  in  the  external 
world,  so  far  as  they  affect  our  sense  organs,  are  converted  into 
the  subjective  changes  of  consciousness.  The  nature  of  this  reac- 
tion constitutes  the  most  difficult  problem  of  physiology  and  psy- 
chology, a  problem  which  perhaps  is  beyond  the  possibility 
of  a  satisfactory  scientific  explanation.  For  it  is  held  that 
the  methods  of  science  are  applicable  only  to  the  investiga- 
tion of  the  objective — that  is,  the  physical  and  chemical — changes 
within  the  nervous  matter,  while  the  psychical  reaction  is  of  a 
nature  that  cannot  be  approached  through  the  conceptions  or 
methods  of  physical  science.  In  other  words,  there  is  a  physicochem- 
ical  mechanism  in  the  brain  matter  which  is  capable  of  giving  us  a 

182 


GENERAL  PHYSIOLOGY  OF  THE  CEREBRUM.         183 

reaction  in  consciousness.  The  methods  of  physiology  are  adapted 
to  the  investigation  of  the  nature  of  this  mechanism,  but  the  reac- 
tion in  consciousness  deals  with  a  something  which  so  far  as  we 
know  is  not  matter  or  energy,  and  which,  therefore,  is  not  within 
the  scope  of  physiological  or,  indeed,  scientific  explanation.  In 
what  follows,  therefore,  attention  is  called  only  to  the  mechanical 
side, — the  facts  that  have  been  discovered  regarding  the  anatomical 
structure  and  the  physical  and  chemical  properties  of  the  nervous 
mechanism. 

The  Histology  of  the  Cortex. — The  finer  structure  of  the 
different  regions  of  the  cortex  has  been  the  subject  of  much  investi- 
gation, but  in  this  connection  it  is  only  necessary  to  recall  the 
elementary  facts  so  far  as  they  are  useful  in  physiological  explana- 
tions. Leaving  aside  differences  in  the  shape  and  stratification 
of  the  cells,  it  is  an  interesting  fact  that  the  cortex  everywhere 
has  a  similar  structure.  It  consists  of  four  or  five  layers  more  or 
less  clearly  distinguishable  (see  Fig.  81). 

1.  The  superficial,  plexiform,  or  molecular  layer,  lying  imme- 
diately beneath  the  pia  mater,  and  having  a  thickness  of  about 
0.25  mm.     In  this  layer,  in  addition  to  the  supporting  neuroglia, 
there  are  found  a  number  of  very  small  nerve  cells  of  several  types 
lying  with  their  processes  parallel  to  the  surface  of  the  brain.     The 
axons  and  dendrites  of  these  small  cells  terminate  within  the  layer, 
so  that  they  take  no  direct  part  in  the  formation  of  the  white 
matter  of  the  brain,  but  have,  probably,  a  distributive  or  associa- 
tive function.     In  this  layer,  also,  end  many  of  the  dendrites  of  the 
larger  nerve  cells  of  the  deeper  layers  and  the  terminal  arboriza- 
tion of  entering  nerve  fibers  (axons)  from  other  regions. 

2.  The  layer  of  pyramidal  cells.     This  layer  is  characterized 
by  the  presence  of  numerous  pyramidal  cells  (see  D,  Fig.  84), 
which  in  general  increase  in  size  in  passing  from  the  upper  to  the 
lower  strata.     The  apices  of  these  cells  are  directed  toward  the 
external  surface.     The  dendrites  from  the  apical  process  terminate 
in  the  molecular  layer,  while  the  axon  arising  from  the  basal  side 
of  the  cell  passes  inwardly  to  constitute  one  of  the  nerve  fibers  of 
the  medullary  portion  of  the  cerebrum.     This  thick  lamina  of 
cells  is  sometimes  subdivided  into  three  layers  of  small,  medium, 
and  large  pyramidal  cells. 

3.  The  granular  or  stellate  layer  composed  of  many  small  cells, 
some  of  which  are  pyramidal  and  some  stellate  in  form,  with  short 
branching  axons.     These  latter  belong  to  Golgi's  second  type  of 
nerve  cell. 

4.  The  deep  pyramidal  layer  or  layer  of  large  or  medium-sized 
pyramidal  cells,  similar  in  form  to  those  in  layer  two,  and  the  axons 
of  which  pass  into  the  medulla  or  white  matter  of  the  cerebrum 
as  nerve  fibers. 


184 


PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 


5.  The  layer  of  fusiform  or  polymor- 
phic nerve  cells.  A  layer  of  cells  whose 
!  form  is  more  irregular  than  that  of  the 
pyramidal  cells,  but  whose  axons  also 
pass  into  the  medullary  portion  of  the 
cerebrum,  while  their  dendrites  stretch 
externally  into  the  layers  of  pyramidal 
cells.  In  this  layer  are  found  also  some 
cells  belonging  to  the  second  type  of 
Golgi  (Martinotti  cells). 

2  The  medulla  of  the  cerebrum.     The 
white   matter   of  the  cerebrum  begins 
immediately  below  the  last-named  layer, 
and  consists  (1)  of  nerve  fibers  which 
originate  from  the  pyramidal  and  poly- 
morphic cells  immediately  exterior  to  it, 
and  which  carry  outgoing  impulses  from 
that  part  of  the  cortex,  and  (2)  of  fibers 
arising  elsewhere  in  the  cortex  or  in  the 

3  lower  portions  of  the  brain,  which  termi- 
nate in  the  cortex  and  carry  the  incoming 
impulses — impulses  which  are  afferent  as 
regards  that  part  of  the  cortex.     The 

4  fibers  in  this  white  matter  may  be  classi- 
fied under  three  heads:  First,  the  projec- 
tion system  (A,  B,  C,  D,  and  E  of  Fig.  82), 
comprising   those    fibers,   afferent   and 
efferent,  which  connect  the  cortex  with 
underlying  parts  of  the  central  nervous 
system, — the  spinal  cord,  medulla,  pons, 

a  midbrain,  or  thalamus.  This  great  pro- 
jection system  emerges,  for  the  most 
part,  through  the  internal  capsule  and 
the  peduncles  of  the  cerebrum.  Second, 
the  association  system.  Certain  parts 
of  the  cortex  are  seemingly  lacking  in  a 
projection  system;  the  fibers  arising  from 
these  parts  do  not  enter  the  capsule  to 
make  connection  with  the  motor  and  sen- 
sory paths  below,  but  pass  to  other 
parts  of  the  cortex,  forming  a  part  of  the 
system  of  association  fibers.  This  sys- 

Fig.  81. — Section  through  the  cortex  of  the  third  frontal  convolution  (Broca's  convolu- 
tion) to  show  the  stratification  of  the  nerve  cells:  1,  The  plexiform  or  molecular  layer;  2. 
the  outer  layer  of  pyramidal  cells;  3,  the  granular  layer;  4,  the  deep  or  inner  pyramidal 
layer;  5,  the  fusiform  or  polymorphic  layer  (from  a  camera  lucida  drawing  by  Mellus). 


L 


GENERAL  PHYSIOLOGY  OF  THE  CEREBRUM. 


185 


Fig.  82. — Schema  of  the  projection  fibers  of  the  cerebrum  and  of  the  peduncles  of  the 
cerebellum;  lateral  view  of  the  internal  capsule  :  A,  Tract  from  the  frontal  gyri  to  the  pons 
nuclei,  and  so  to  the  cerebellum  (frontal  cerebro-cortico-pontal  tract)  ;  B,  the  motor 
(pyramidal)  tract ;  C,  the  sensory  (lemniscus)  tract ;  D,  the  visual  tract ;  E,  the  auditory 
tract ;  F,  the  fibers  of  the  superior  peduncle  of  the  cerebellum  ;  G,  fibers  of  the  middle  pedun- 
cle uniting  with  A  in  the  pons  ;  H,  fibers  of  the  inferior  peduncle  of  the  cerebellum  ;  J,  fibers 
between  the  auditory  nucleus  and  the  inferior  colliculus  ;  K,  motor  (pyramidal)  decussation 
in  the  bulb ;  Vt,  fourth  ventricle.  The  numerals  refer  to  the  cranial  nerves. — (Modified 
from  Starr.) 


Fig.  83. — Lateral  view  of  a  human  hemisphere,  showing  the  bundles  of  association 
fibers  (Starr)  :  A,  A,  Between  adjacent  gyri;  B,  between  frontal  and  occipital  areas;  C, 
between  frontal  and  temporal  areas,  cingulum  ;  D,  between  frontal  and  temporal  areas, 
fasciculus  uncinatus  ;  E,  between  occipital  and  temporal  areas,  fasciculus  longitudinalia 
inferior  ;  C.N,  caudate  nucleus  ;  O.T,  thalamus. 

tern  may  be  defined  as  comprising  those  fibers  which  connect  one 
part  of  the  cortex  with  another  (Fig.  83).     There  are  short  associ- 


186  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

ation  tracts  (A,  A)  connecting  neighboring  convolutions  and  long 
tracts  passing  from  one  lobe  to  another.  Third,  the  commissural 
system,  consisting  of  association  fibers  that  cross  the  mid-line  and 
connect  portions  of  one  cerebral  hemisphere  with  the  cortex  of  the 
other.  These  fibers  make  up  the  commissural  bands,  known  in 
gross  anatomy  as  the  corpus  callosum,  anterior  white  commissure, 
fornix,  etc. 

Physiological  Deductions  from  the  Histology  of  the  Cortex. 
— Cajal*  especially  lays  stress  upon  some  anatomical  features  which 
seem  to  justify  certain  generalizations  of  a  physiological  nature.  In 
the  first  place,  every  part  of  the  cortex  receives  incoming  impulses 
and  gives  rise  to  outgoing  impulses.  Every  part  of  the  cortex  is, 
therefore,  both  a  termination  of  some  afferent  path  and  the  begin- 
ning of  some  efferent  path;  it  is,  in  other  words,  a  reflex  arc  of 
a  greater  or  less  degree  of  complexity.  We  may  suppose  that 
every  efferent  discharge  from  any  part  of  the  cortex  is  occasioned 
by  afferent  impressions  reaching  that  point  from  some  other  part 
of  the  nervous  system.  Whether  or  not  there  is  such  a  thing  as 
absolutely  spontaneous  mental  activity  cannot  be  determined  by 
physiology,  but  on  the  anatomical  side  at  least  all  the  structures 
exhibit  connections  that  fit  them  for  reflex  stimulation,  and  many 
of  our  apparently  spontaneous  acts  must  be  of  this  character. 
Secondly,  all  parts  of  the  cortex  exhibit  an  essentially  similar 
structure.  Modern  physiology  has  taught  that  different  parts 
of  the  cerebrum  have  different  functions,  but  the  differentiation 
in  structure  which  usually  accompanies  a  specialization  in  func- 
tion is  not  at  first  very  evident.  Definite  differences  in  the 
thickness  of  the  layers,  in  the  size  or  shape  of  the  cells,  or  in  the 
character  of  the  fibrillation,  have  been  pointed  out  (see  p.  229),  but 
it  is  perhaps  something  of  a  disappointment  to  find  so  little  of  an 
anatomical  distinction  between  structures  whose  reaction  in  con- 
sciousness may  be  separated  so  widely.  Numerous  special  studies 
made  upon  the  lamination  of  different  parts  of  the  human  cortex 
(see  p.  229),  and  comparative  observations  upon  the  cerebral  cor- 
tex in  different  vertebrates,  have  served  to  give  an  anatomical 
foundation  for  various  interesting  speculations  which  subsequent 
work  may  or  may  not  confirm,  f  It  is  pointed  out  that  if  we  omit 
the  outer  or  molecular  layer  the  other  cells  of  the  cortex  fall  into 
three  groups,  namely,  the  granular  layer  (3  in  Fig.  81),  the  supra- 
granular  layer  (2),  comprising  the  pyramidal  cells  external  to  the 

*  Cajal,  "Les  nouvelles  idees  sur  la  structure  du  systeme  nerveux,  etc.," 
Paris,  1894. 

or 

Van 


GENERAL  PHYSIOLOGY  OF  THE  CEREBRUM. 


187 


granular  layer,  and  the  infragranular  layer  (4  and  5),  comprising 
the  pyramidal  and  fusiform  cells  internal  to  the  granular  layer. 
Comparison  of  the  cerebral  cortex  in  the  brains  of  the  different 
vertebrates  indicates  that  the  supragranular  cells  have  appeared 
relatively  late  in  the  phylogeny  of  the  vertebrates,  and  have 
reached  their  greatest  development  in  the  human  brain.  The 
suggestion  occurs,  therefore,  that  these  cells  have  a  different  func- 
tional significance  from  those  in  the  infragranular  layer.  It  has 
been  supposed  that  the  supragranular  cells  mediate  the  so-called 


Fig.  84. — A-D,  Showing  the  phylogenetic  development  of  mature  nerve  cells  in  a 
series  of  vertebrates:  a-e,  the  ontogenetic  development  of  growing  cells  in  a  typical  mam- 
mal (in  both  cases  only  pyramidal  cells  from  the  cerebrum  are  shown) ;  A,  frog;  B,  lizard; 
C,  rat;  Z>,  man;  a,  neuroblast  without  dendrites;  6,  commencing  dendrites;  c,  dendrites 
further  developed;  d,  first  appearance  of  collateral  branches;  e,  further  development  of 
collaterals  and  dendrites. — (From  Ratndn  y  Cajal.) 

higher  psychical  processes,  which  characterize  man  and  the  related 
mammalia  as  compared  with  the  lower  vertebrates.  The  infra- 
granular  cells,  on  the  other  hand,  constitute  a  primitive  layer  which 
has  obvious  connections,  through  projection  fibers,  with  the  under- 
lying parts  of  the  brain  and  of  the  body  at  large.  These  cells 
form,  therefore,  a  mechanism  through  which  the  brain  is  connected 
directly  with  the  rest  of  the  body,  and  through  which  the  older 


188 


PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 


instinctive  reactions  are  controlled.  In  the  matter  of  lami- 
nation and  distinct  variations  in  size  and  appearance  of  the 
strata  of  cells  and  fibers  the  human  cortex  shows  a  greater  dif- 
ferentiation than  in  the  lower  animals,  and  it  is  especially 
characterized  by  a  large  development  of  what  are  known  as 
associational  areas  (p.  223),  particularly  in  the  frontal  lobe. 
In  the  third  place,  the  central  nervous  system  throughout  the 
vertebrates  is  constructed  upon  the  same  lines,  a  mechanism  of 
interconnecting  neurons.  There  is  a  vast  difference  in  the  men- 


*' 


Fig.  85. — Sections  through  corresponding  parts  of  the  cortex  in:  a,  Man;  6,  dog; 
and  c,  mole,  to  show  the  greater  separation  of  tne  nerve  cells  in  the  higher  animals. — • 
(Bethe,  after  Nissl.) 

tal  activity  of  a  frog  and  a  man,  but  the  cortex  of  the  cerebrum 
shows  a  fundamental  similarity  in  structure  in  the  two  cases. 
In  addition  to  the  variations  in  stratification  or  lamination  referred 
to  above  one  general  distinction  that  comparative  anatomy  is  able 
to  make  is  that  in  the  higher  animals  the  greater  mental  develop- 
ment is  associated  with  a  greater  complexity  and  richness  in  the  con- 


GENERAL  PHYSIOLOGY  OF  THE  CEREBRUM.         189 

nections  of  the  neurons.  As  shown  in  Figs.  84  and  85,  the  number  of 
processes,  particularly  the  dendritic  processes,  is  much  greater  in 
the  cortical  cells  of  the  higher  animals;  or,  to  put  this  fact  in  another 
way,  the  number  of  cells  in  the  cortex  of  the  higher  animals  is  much 
less  for  an  area  of  the  same  size  than  in  lower  animals.  The  amount 
of  in-between  substance  or  the  richness  of  the  network  of  processes 
is  increased.  This  anatomical  fact  would  indicate  that  the  greater 
mental  activity  in  the  higher  animals  is  dependent,  in  part,  upon  the 
richer  interconnection  of  the  nerve  cells,  or,  expressed  physiologic- 
ally, our  mental  processes  are  characterized  by  their  more  numer- 
ous and  complex  associations.  A  visual  or  auditory  stimulus  that, 
in  the  frog,  for  instance,  may  call  forth  a  comparatively  simple 
motor  response,  may  in  man,  on  account  of  the  numerous  associa- 
tions with  the  memory  records  of  past  experiences,  lead  to  psychi- 
cal and  motor  responses  of  a  much  more  intricate  and  indirect 
character.  From  a  physiological  standpoint  these  responses  are 
of  the  order  of  reflex  actions.  They  must  be  investigated  and,  if 
possible,  explained  from  this  point  of  view.  The  problem  is  diffi- 
cult and  complex.  The  methods  that  have  been  employed  for  its 
solution  are  described  and  illustrated  in  the  summary  of  results 
given  in  the  following  pages,  but  it  is  obvious  that  new  methods  of 
approach  are  much  needed.  One  such  attempt  that  is  now  being 
made  is  known  under  the  term  of  " conditioned  reflexes." 

The  Phenomenon  of  Conditioned  Reflexes. — The  usual  reflexes 
effected  through  the  spinal  cord  and  the  lower  centers  of  the  brain 
are  of  a  fixed  nature.  Light  thrown  on  the  retina  causes  always  a 
constriction  of  the  pupil;  a  touch  applied  to  the  cornea  causes  a 
winking  movement ;  acid  in  the  mouth  is  followed  by  a  secretion  of 
saliva.  These  and  similar  reflexes  are  essentially  invariable 
responses  to  appropriate  stimuli,  and  the  mechanism  involved,  the 
reflex  arc,  is  an  inherited  structure  already  elaborated  for  use. 
Pawlow  designates  such  acts  as  unconditioned  reflexes.  In  contrast 
to  them  he  describes  a  class  of  reflexes  obtained  through  the  cortex 
of  the  cerebrum  which  he  calls  conditioned  reflexes,  because  they 
may  be  elaborated  under  certain  conditions.  They  may  be 
brought  into  existence  by  a  process  of  training  or  education,  and 
they  are  subject  to  various  forms  of  inhibition,  internal  and  external. 
He  has  made  a  special  study  of  these  reflexes  in  connection  with 
the  salivary  glands.  If  a  certain  sensory  stimulus  is  given,  for 
example,  a  note  of  800  vibrations  per  second,  it  has  no  effect  on 
the  flow  of  saliva.  But  if  repeatedly  the  salivary  gland  is  stimu- 
lated by  acid  or  food  simultaneously  with  the  sounding  of  the 
note  a  conditioned  reflex  will  be  established,  and  the  note,  when 
given  alone,  will  cause  a  flow  of  saliva.  When  this  conditioned 


190  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

reflex  is  first  established  it  may  be  obtained  also  with  neighboring 
tones,  but  with  training  the  reflex  becomes  more  and  more  special- 
ized, so  that  finally  as  small  an  interval  as  one-eighth  of  a  tone 
may  be  differentiated — a  sound  of  800  vibrations  causes  a  flow 
of  saliva  while  a  sound  of  812  vibrations  is  ineffective.  The 
process  of  differentiation  is  explained  as  being  due  to  an  internal 
inhibition,  as  shown  by  the  following  experiment.  If  a  tone  of  812 
vibrations  is  sounded  no  saliva  is  obtained,  and  if  immediately 
afterward  the  effective  tone,  800  vibrations,  is  sounded  no  effect 
follows.  Only  after  a  wait  of  fifteen  to  twenty  minutes  does  the 
tone  of  800  again  cause  a  flow  of  saliva.  He  argues  from  this  that 
the  tone  of  812  vibrations  is  accompanied  by  a  process  of  inhibi- 
tion, whose  effect  passes  off  only  after  some  minutes.  By  these 
objective  methods  Pawlow*  has  brought  to  light  some  interesting 
peculiarities  in  the  action  of  the  cortex,  and  has  established  a 
method  by  means  of  which  it  may  be  possible  to  study  the  nature 
and  development  of  the  mechanisms  elaborated  in  the  plastic 
cortical  centers  by  education  and  experience  during  the  life  of  the 
individual. 

Extirpation  of  the  Cerebrum. — One  of  the  methods  used  in 
physiology  to  determine  the  general  functional  value  of  the  cerebral 
hemispheres  has  been  to  remove  them  completely,  by  surgical 
operation,  and  to  study  the  effect  upon  the  psychical  responses  of 
the  animal.  Upon  the  cold-blooded  animals  and  the  birds  the 
operation  may  be  performed  with  ease,  but  in  these  animals  the 
positive  results  are  not  striking  and  the  experiments  are  valuable 
chiefly  for  their  negative  results.  If  the  cerebral  hemispheres  are 
removed  from  the  frog,  for  example,  the  animal  after  recovering 
from  the  immediate  effects  of  the  operation — that  is,  the  effects 
of  the  anesthetic  and  the  shock — shows  surprisingly  little  difference 
from  the  normal  animal.  It  maintains  a  normal  posture  and  shows 
no  loss  at  all  in  its  power  of  equilibration.  When  placed  on  its 
back  it  quickly  regains  its  usual  position.  If  thrown  into  water 
it  swims  to  a  solid  support  and  crawls  out  like  a  normal  animal. 
It  jumps  when  stimulated  and  is  careful  to  avoid  obstacles  placed 
in  its  way,  showing  that  its  visual  reflexes  are  not  impaired.  It 
is  said,  however,  that  the  more  complicated  reactions  that  depend 
upon  the  memory  of  past  experiences  or  the  instincts  are  absent  or 
imperfect.  This  latter  peculiarity  is  manifested  most  impressively 
in  birds  (pigeons)  after  removal  of  a  part  or  all  of  the  cerebrum.  As 
a  result  of  such  an  operation,  the  nervous,  active  animal  is  changed 
at  once  to  a  stupid,  lethargic  creature  which  reacts  only  when 

*  Pawlow,  "Livre  jubilaire  du  Professeur  Ch.  Richet,"  1912,  p.  325.  See 
also  Morgulis,  "The  Journal  of  Animal  Behavior,"  4,  362,  1914. 


GENERAL  PHYSIOLOGY  OF  THE  CEREBRUM.         191 

stimulated.     It  sits  in  a  drowsy   attitude,  with  its  head  drawn  in 
to  the  shoulders,  its  eyes  closed,  and  its  feathers  slightly  erected; 
occasionally   it  will  open  its  eyes,  stretch  the  neck,  gape,  preen 
its  feathers  perhaps,  and  then  sink  back  into  its  somnolent  attitude. 
The  animal  in  this  condition  maintains  its  equilibrium  perfectly, 
flies  well  if  thrown  into  the  air  and  perches  comfortably  upon  a 
narrow  support.     It  may  be  kept  alive  apparently  indefinitely  by 
appropriate  feeding  and  so  long  as  it  is  well  fed  retains  its  stupid 
and  impassive  appearance.     If  allowed  to  starve  for  a  while  it 
becomes  restless  from  the  effects  of  hunger,  may  walk  to  and  fro, 
and  peck  aimlessly  at  the  ground.     If  surrounded  by  grain  it  may 
peck  at  the  separate  grains,  but  never  actually  seizes  one  in  its 
beak  and  swallows  it.     The  striking  defect  in  these  animals  is  the 
loss  of  those  responses  that  depend  upon  memory  of  past  or  in- 
herited experiences.     Its  motor  reactions  are  all  of  a  simple  kind. 
If  placed  upon  a  hot  plate  it  will,  for  a  time,  lift  first  one  foot,  then 
the  other,  and  finally  squat,  but  never  flies  away.     When  dosing 
a   loud  noise   awakens  it,  but  it   exhibits  no  signs  of  fear,  and 
quickly  relapses  into  somnolence  when  the  auditory  stimulus  ceases. 
The  one  positive  conclusion  that  we  may  draw  from  the  behavior 
of  these  animals  is  that  in  them  the  cerebrum  is  the  organ  in 
which  the  memory  associations  are  mediated,  and  that  when  it 
is  removed  the  actions  of  the  animal  become  much  more  direct 
and  predictable,  since  the  stimulus  awakens  no  associations  with 
past  experiences.     The  complete  removal  of  the  cerebrum  in  mam- 
mals is  attended  with  more  difficulty.     When  taken  out  at  once 
by  a  single  operation,  the  animal  survives  but  a  short  time  and 
the  permanent  effects  of  the  operation  cannot  be  detected.    Goltz,* 
however,  has  succeeded,  in  dogs,  in  removing  by  a  peculiar  opera- 
tion all  of  the  cerebral  cortex.     The  operation  was  performed  in 
several  successive  stages  with  an  interval  of  several  months  between. 
In  the  most  successful  experiment  the  animal  was  kept  alive  for 
a  year  and  a  half  and  the  postmortem  examination  showed  that 
all  of  the  cortex  had  been  removed  except  a  small  portion  of  the 
tip  of  the  temporal  lobe,  and  this  latter,  since  its  connection  with 
the  other  parts  of  the  brain  had  been  destroyed,  was,  of  course, 
functionless.     In  addition,  a  large  part  of  the  corpora  striata  and 
the  thalami  and  a  small  portion  of  the  midbrain  had  been  re- 
moved.    The  behavior  of  this  animal  was  studied  carefully.    After 
the  immediate  effects  of  the  operation — paralysis,  etc. — had  disap- 
peared the  animal  moved  easily;  in  fact,  showed  a  tendency  to  keep 
moving  continually.    There  was  no  permanent  paralysis  of  the  so- 
called  voluntary  movements.     He  answered  to  sensory  stimuli  of 

*  Goltz,  "Archiv  f .  die  gesammte  Physiologic,"  51,  570,  1892. 


192  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

various  kinds,  but  not  in  an  intelligent  way.  If,  for  instance,  a 
painful  stimulus  was  applied  to  the  skin,  he  would  growl  or  bark, 
and  turn  his  head  toward  the  place  stimulated;  but  did  not  attempt 
to  bite.  No  caressing  could  arouse  signs  of  pleasure,  and  no 
threatening  signs  of  fear  or  anger.  Like  the  pigeon,  the  most  con- 
spicuous defect  in  the  animal  was  a  lack  of  intelligent  response, — 
that  is,  the  responses  to  sensory  stimuli  were  simple,  and  evidently 
did  not  involve  complex  associations  with  past  experiences.  His 
memory  records,  for  the  most  part,  had  been  destroyed.  Goltz 
records  that  when  starved  he  showed  signs  of  hunger,  and  that 
eventually  he  learned  to  feed  himself  when  his  nose  was  brought 
into  contact  with  the  food,  although  he  was  not  able  to  recognize 
food  placed  near  him.  He  would  reject  food  with  a  disagreeable 
taste.  When  sleeping  he  gave  no  signs  of  dreaming,  differing  in 
this  respect  from  normal  dogs.  On  human  beings  observations  of 
a  similar  character  have  been  made  on  children  born  without  the 
brain.  In  one  interesting  case*  of  this  kind,  in  which  autopsy  re- 
vealed a  total  destruction  of  the  cerebral  hemispheres,  the  child 
lived  for  nearly  four  years.  During  that  time  no  signs  of  intelli- 
gence could  be  detected.  The  child  never  showed  any  recogni- 
tion of  its  mother  and  lay  for  the  most  part  in  a  somnolent  condi- 
tion without  movement,  the  arms  and  legs  showing  also  a  condition 
of  contracture.  No  cutaneous  or  general  sensibility  could  be 
determined. 

Localization  of  Functions  in  the  Cerebrum. — When  the 
belief  was  established  that  the  cerebrum  is  the  organ  of  the  higher 
psychical  activities  there  arose  naturally  the  question  whether  dif- 
ferent parts  of  the  cortex  have  different  functions  corresponding 
to  the  various  faculties  of  the  mind,  or  whether  the  cerebrum  is 
functionally  equivalent  throughout,  in  the  same  sense,  for  instance, 
as  the  liver.  This  question  of  the  localization  of  functions  in  the 
brain  (cerebrum)  has  been  much  debated,  but  the  most  interesting 
and  important  discussions  upon  the  subject  belong  to  the  nine- 
teenth century.  About  the  beginning  of  the  century  Franz  Joseph 
Gall,  at  that  tune  a  physician  in  Vienna,  began  to  teach  publicly  his 
well-known  system  of  cranioscopy  or,  as  it  was  later  designated  by 
his  chief  disciple  (Spurzheim),  system  of  phrenology,  f  Gall,  from 
his  early  youth,  was  possessed  with  the  idea  that  the  different  facul- 
ties of  the  mind  are  mediated  through  different  parts  of  the  brain, 
that  in  it  we  have  to  deal  not  with  a  single,  but  with  a  plurality  of 
organs.  This  belief  was  in  opposition  to  the  current  ideas  of  his 

*  Edinger  and  Fischer,  "Pfliiger's  Archiv,"  152,  535,  1913. 
t  Gall  (and  Spurzheim),  "Recherches  sur  la  systeme  nerveux  en  general 
et  sur  celui  du  cerveau  en  particulier,"  1810-19. 


GENERAL  PHYSIOLOGY  OF  THE  CEREBRUM.         193 

times  and  Gall  devoted  his  entire  life  to  an  earnest  effort  to  estab- 
lish and  popularize  his  views.  He  and  his  disciples  contributed 
many  very  important  facts  to  our  knowledge  of  the  finer  anatomy 
of  the  brain;  but,  so  far  as  the  view  of  separate  organs  in  the 
cerebrum  is  concerned,  the  methods  that  he  employed,  although 
perhaps  the  only  ones  that  he  could  make  use  of  at  that  time, 
have  since  been  demonstrated  to  be  fallacious  when  used  as  he 
used  them.  He  conceived  that  the  more  developed  any  given 
mental  quality  is  the  larger  will  be  the  organ  representing  it  in 
the  cerebrum,  and  since  the  cranium  fits  closely  to  the  cerebrum 
the  relative  prominence  of  the  parts  of  the  cerebrum  may  be  judged 
by  a  study  of  the  exterior  of  the  skull.  This  method  of  study  con- 
stituted the  essential  feature  of  cranioscopy  or  phrenology,  and 
by  observation  upon  people  with  particularly  marked  mental 
qualities  Gall  and  his  disciples  supposed  that  they  had  located  the 
organs  for  thirty-five  different  faculties.  While  the  general  idea 
of  this  method  may  be  defended,  it  is  obvious  that  the  application 
of  it  scientifically,  so  that  positive  and  demonstrable  results  can 
be  obtained,  is  practically  impossible.  The  system  of  phrenology 
and  its  methods  quickly  fell  into  disrepute,  since  they  were  ex- 
ploited by  frauds  and  charlatans.  Gall's  ideas  in  the  begin- 
ning excited  the  greatest  interest,  but  it  seems  that  he  was  never 
able  to  convince  the  majority  of  the  scientific  men  of  his  day 
of  the  conclusiveness  of  his  results.  At  the  time  that  he  was 
teaching  his  doctrines  in  Paris,  where  he  spent  the  later  years  of 
his  life,  Flourens  began  his  celebrated  experimental  work  upon  the 
functions  of  the  brain, — work  which  was  mainly  instrumental  in 
convincing  physiologists  that  the  cerebrum  is  a  single  organ, 
functionally  equivalent  in. all  of  its  parts.*  Flourens'  chief  ex- 
periments were  made  upon  pigeons,  and  in  these  animals  he  found 
that  successive  ablations  of  parts  of  the  cerebrum  from  before 
backward  or  from  side  to  side  were  not  followed  by  a  corresponding 
series  of  defects  in  the  animals'  psychical  life.  On  the  contrary, 
when  the  quantity  of  brain  substance  removed  was  sufficiently 
large,  all  these  qualities  went  at  once.  The  choice  of  animals 
for  these  experiments  was  an  unfortunate  one,  but  the  results 
were  corroborated  in  part  by  a  number  of  instances  in  which  human 
beings  by  accident  or  wounds  in  battle  had  lost  a  part  of  the  brain 
without  any  apparent  defect  in  their  mental  powers.  Therefore 
toward  the  middle  of  the  nineteenth  century  the  prevalent  view 
in  physiology  was  that  the  cerebrum  is  functionally  equivalent  in 
all  of  its  parts.  One  fact  was  known  in  medicine  at  that  time 

*  Flourens,  "Recherches  expeVimentales  sur  les  proprietes  et  les  fonctions 
du  systeme  nerveux  dans  les  animaux  verte"bre"s,"  1824. 
13 


194  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

which  distinctly  contradicted  this  belief, — namely,  that  an  injury 
to  the  region  of  the  third  frontal  convolution  in  man,  on  the 
left  side,  causes  a  loss  of  articulate  speech  (motor  aphasia).  But 
this  fact,  so  significant  to  us  now,  was  not  properly  valued  at 
the  time.  The  beginning  of  our  modern  views  of  cerebral  localiza- 
tion is  found  in  the  work  of  Fritsch  and  Hitzig*  (1870),  in  which 
they  exposed  and  stimulated  electrically  the  cortex  cerebri  in 
dogs.  They  observed  that  stimulation  of  certain  definite  areas, 
particularly  in  the  sigmoid  gyms,  gave  distinct  and  constant 
movements  in  the  limbs,  face,  etc.  (see  Fig.  86).  This  work 
was  followed  quickly  by  experiments  of  a  similar  kind  made 
by  numerous  observers,  in  which  the  cerebrum  was  stimulated  in 
various  animals  and  finally  in  man.  In  addition,  the  method  of 
ablation  of  these  areas  was  employed  with  subsequent  study  of 
the  animal  in  regard  to  the  motor  or  sensory  defects  resulting 
therefrom,  and  the  results  obtained  were  further  extended  by 
careful  autopsies  upon  human  beings  in  whom  paralyses  of  various 
kinds  and  sensory  defects  were  associated  with  more  or  less  defi- 
nite lesions  of  the  cerebrum.  The  first  outcome  of  this  work  was 
to  lead  to  an  extreme  view  of  localization  of  function  in  the  brain, 
in  which  the  different  motor  and  sensory  areas  were  definitely 
circumscribed  and  separated  one  from  the  other,  making  the 
cerebrum  a  plurality  of  organs,  to  use  Gall's  term.  The  more 
recent  work  has  tended  to  modify  these  extreme  views  of  local- 
ization and  to  emphasize  the  fact  that  histologically  and  physio- 
logically the  entire  cerebrum  is  connected  so  intimately,  part  to 
part,  that,  although  the  different  regions  mediate  different  func- 
tions, nevertheless  an  injury  or  defect  in  one  part  may  influence 
to  some  extent  the  functional  value  of  all  other  regions  in  the 
organ.  The  general  idea  of  a  localization  of  function  has  been 
accepted,  but  the  modern  view  is  that  the  cerebrum  is  com- 
posed of  a  plurality  of  organs,  not  completely  separated  one 
from  the  other,  as  taught  by  Gall,  but  intimately  associated 
and  to  a  certain  extent  dependent  one  on  another  for  their  full 
functional  importance.  The  functional  interrelation  of  different 
parts  of  the  cortex  is  shown  by  the  fact  that  a  cortical  lesion  at  one 
point  may  involve  not  only  the  activity  primarily  connected  with 
that  region,  but  may  influence  also  the  functional  performance  of 
far  distant  uninjured  parts  of  the  cortex  or  even  of  the  underlying 
portions  of  the  central  nervous  system,  the  medulla,  and  the 
spinal  cord.  Monakow  states,  for  example,  that  in  lesions  of  the 
pyramidal  system  we  may  observe  among  the  temporary  symp- 

•*  Fritsch  and  Hitzig,  "Archiv  f.  Anatomie  und  Physiologic  und  wissea- 
schaftliche  Medizin,"  1870,  300. 


GENERAL  PHYSIOLOGY  OF  THE  CEREBRUM. 


195 


toms  accompanying  the  hemiplegia  a  disturbance  of  the  swallowing 
reflex  or  a  diminution  in  the  spinal  reflexes.  The  nuclei  in  the 
medulla  and  the  cord  suffer  a  diminution  in  irritability,  although 
not  directly  involved  in  the  lesion.  Monakow  designates  this  re- 
sult or  condition  under  the  term  diaschisis*  which  he  defines  as  a 
diminution  in  irritability  within  the  whole  connected  functional 
complex  without  anatomical  lesion.  It  must  also  be  borne  in  mind 
in  this  connection  that  most  of  the  efforts  made  hitherto  to  localize 
the  functional  activities  of  the  brain  have  had  reference  chiefly  to 
planes  of  separation  vertical  to  the  cortex.  As  indicated  on  p.  187, 


Fig.  86. — To  show  the  motor  areas  in  the  dog's  brain  as  originally  determined  by  Fritsch 
and  Hitzig:  s,  Sigmoid  gyrus;  A,  center  for  the  neck  muscles;  -K,  center  for  the  extensors  and 
adductors  of  the  forelimb;  +,  center  for  the  flexors  and  rotation  of  forelimb;  #,  center  for  the 
hind  limb;  Q— O.  center  for  the  muscles  innervated  by  the  facial. 


recent  investigations  have  indicated  that  it  will  be  necessary  to 
consider  also  the  separation  of  function  along  horizontal  planes 
(von  Valkenburg).  That  is  to  say,  it  seems  quite  possible  that  the 
several  strata  in  the  cortex,  such  as  the  granular,  the  infra- 
granular,  and  the  supragranular  layers  may  mediate  different  ac- 
tivities of  the  brain,  or  even  different  psychical  functions. 

*  von  Monakow,  "Ergebnisse  der  Physiologie,"  vol.  xiii.,  1913. 


196 


PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 


The  Motor  Area. — The  first  experiments  of  Fritsch  and  Hitzig 
disclosed  the  location  of  a  cortical  region  in  the  dog  which  upon 
stimulation  gave  definite  movements.  The  later  experiments  of 
Ferrier,  Schafer,  Horsley,  and  Beevor,  particularly  upon  the  apes, 
gave  reason  for  believing  that  this  motor  area  surrounds  the 
central  sulcus  of  Rolando  and  extends  inward  upon  the  mesial 
surface  of  the  cerebrum.  Its  exact  boundaries  marked  out  by 


Eyelid  /Closure 

Nose   °f j"»  Opening 


cords 


Fig.  87. — Location  of  motor  areas  in  brain  of  chimpanzee. — (Sherrington  and  Green- 
baum.) The  extent  of  the  motor  areas  is  indicated  by  stippling;  it  lies  entirely  in  front 
of  the  fissure  of  Rolando  (sulcus  centralis).  Much  of  the  motor  area  is  hidden  in  the  sulci. 
The  regions  marked  eyes  indicate  the  areas  whose  stimulation  gives  conjugate  movements 
of  the  eyeballs.  It  is  doubtful,  however,  whether  these  represent  motor  areas  proper. 

careful  stimulation  of  the  region  in  monkeys  was  more  or  less 
verified  upon  man,  since  in  operations  upon  the  brain  it  was 
often  necessary  to  stimulate  the  cortex  in  order  to  localize  a 
given  motor  area.  By  these  means  charts  have  been  made 
showing  the  cortical  area  for  the  musculature  of  each  part  of 
the  body.  It  was  found  that  in  general  the  distribution  of 
the  areas  lies  along  the  central  sulcus  of  Rolando  and  follows 
the  order  of  the  cranial  and  spinal  nerves.  Within  each  area 
smaller  centers  may  be  located  by  careful  stimulation;  thus,  the 
hand  and  arm  area  may  be  subdivided  into  centers  for  the  wrist, 
fingers,  thumb,  etc.  Sherrington  and  Greenbaum,*  making 

*" Reports  of  the  Thompson- Yates  and  Johnson  Laboratories,"  4,  351, 
1902;  5,  55,  1903.  Also  Ley  ton  and  Sherrington,  -"Quarterly  Journal  of 
Exp.  Physiology,"  11,  135,  1917. 


GENERAL  PHYSIOLOGY  OF  THE  CEREBRUM. 


197 


use  of  electrical  stimulation,  unipolar  method,  have  explored 
carefully  the  motor  areas  in  the  monkey.  They  state  that 
these  areas  do  not  extend  back  of  the  central  sulcus,  but  lie 
chiefly  along  the  anterior  central  convolution,  as  represented 
in  Figs.  87  and  88,  and  extend  for  only  a  small  distance  on  to 
the  mesial  surface  of  the  cerebrum.  The  area  thus  delimited 
by  physiological  experiments  is  the  region  from  which  arises 
the  pyramidal  system  of  fibers,  and  clinical  experience  has 


Sulc.  General. 


Sutlc-ccdLoso 


8ulc,parteCo 


Svlc.precen6r.marg. 


Sulc-calcarin. 


C.S.3.  dd. 


Fig.  88. — To  show  extension  of  motor  areas  on  to  the  mesial  surface,  brain  of  chim- 
panzee.— (Sherrington  and  (jreenbaum).  Mesial  surface  of  left  hemisphere:  Stippled  region 
marked  LEG  gives  the  motor  area  for  lower  limb;  /,  «,  and  h  indicate  regions  from  which 
movements  were  obtained  occasionally  with  strong  stimuli;  /,  foot  and  leg;  st  shoulder  and 
chest;  h,  thumb  and  fingers.  The  shaded  area  marked  EYES  indicates  a  region  stimulation 
of  which  gives  conjugate  movements  of  the  eyes. 

shown  that  lesions  in  this  part  of  the  cortex  are  accompanied 
by  a  paralysis  of  the  muscles  on  the  other  side,  particularly 
in  the  limbs.  Pathological  or  experimental  lesions  here,  more- 
over, are  followed  by  a  degeneration  of  the  pyramidal  neurons, 
— a  degeneration  which  extends  to  the  termination  of  the  neurons 
in  the  cord.  With  these  data  we  can  construct  a  fairly  complete 
account  of  the  mechanism  of  voluntary  or  non-automatic  move- 
ments. The  initial  outgoing  or  efferent  impulses  arise  in  the  large 
pyramidal  cells  of  the  motor  areas,  and  proceed  along  the  axons  of 
their  neurons  to  the  motor  nuclei  of  the  cranial  or  spinal  nerves. 
The  neurons  of  the  pyramidal  tract  constitute  the  motor  tract  for 
voluntary  movements;  a  lesion  anywhere  along  this  tract  causes 
paralysis,  more  or  less  complete,  and  on  the  other  side  of  the  body  in 
general,  if  the  lesion  is  anterior  to  the  decussation.  The  path  of  the 
motor  fibers  is  represented  in  the  schema  given  in  Fig.  89.  Arising 
in  the  cortex,  they  take  the  following  route  (see  also  Fig.  82,  B) : 


PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

1.  Corona  radiata. 
2    Internal  capsule. 

3.  Peduncle  of  cerebrum. 

4.  Pons  Varolii,  in  which  they  are  broken  into  a  number  of 

smaller  bundles  by  the  fibers  of  the  middle  peduncle  of 
the  cerebellum  (brachium  pontis).  In  this  region,  also, 
some  of  the  fibers  cross  the  mid-line,  to  end  in  the 
motor  nuclei  of  the  cranial  nerves:  Third,  fourth,  fifth, 
sixth,  and  seventh. 

5.  Anterior  pyramids. 

6.  Pyramidal  decussation. 

7.  Anterior  and  lateral  pyramidal  fasciculi  in  the  cord. 
After  ending  in  the  motor  nuclei  of  the  cranial  or  spinal  nerves  the 

path  is  continued  by  a  second  neuron  from  these  nuclei  to  the  mus- 
cles. The  entire  path  involves,  therefore,  at  a  minimum,  two  neu- 
rons, and  injury  to  either  will  cause  paralysis  of  the  corresponding 
muscles. 

Difference  in  the  Paralysis  from  Injury  to  the  Spinal  and  the 
Pyramidal  Neuron. — With  regard  to  the  musculature  of  the  limbs 
especially  a  difference  has  been  observed  in  the  paralysis  caused  by 
injury  to  the  spinal  and  pyramidal  (cerebrospinal)  neurons, 
respectively.  Lesions  of  the  anterior  root  cells  in  the  cord 
or  of  the  axons  arising  from  them  cause  complete  paralysis  of 
the  corresponding  muscles,  since  these  muscles  are  then  re- 
moved not  only  from  voluntary  control,  but  also  from  reflex 
effects.  The  muscles  are  entirely  relaxed  and  in  time  exhibit 
a  more  or  less  complete  atrophy.  When  the  pyramidal  neurons 
are  affected,  as  in  the  familiar  condition  of  hemiplegia  resulting 
from  a  unilateral  lesion  of  the  motor  cortex,  there  is  paralysis  as 
regards  voluntary  control,  but,  the  spinal  neuron  being  intact,  the 
muscles  are  still  subject  to  reflex  stimulation  through  the  cord, 
especially  to  the  so-called  tonic  impulses.  Under  these  conditions, 
especially  if  the  lesion  is  in  the  cord,  it  is  frequently  noticed  that  the 
paralyzed  muscles  are  thrown  into  a  state  of  continuous  contraction, 
contracture,  in  which  they  exhibit  a  spastic  rigidity.  This  fact, 
therefore,  may  be  used  in  diagnosing  the  general  location  of  the 
lesion.  A  satisfactory  explanation  of  the  cause  of  the  tonic  con- 
traction has  not  been  furnished.  It  may  be  due  to  uncontrolled 
reflex  excitation  of  the  spinal  neurons,  or,  as  suggested  by  Van 
Gehuchten,  to  the  action  of  the  indirect  motor  path  by  way  of  the 
rubrospinal  tract  (fasciculus  intermediolateralis). 

Is  the  Pyramidal  System  the  Only  Means  of  Voluntary  (Cor- 
tical) Control  of  the  Muscles? — Much  discussion  has  arisen 
regarding  this  question.  It  is,  in  fact,  one  of  those  questions  of 
nervous  mechanism  in  which  experiments  upon  lower  animals 


GENERAL    PHYSIOLOGY    OF    THE    CEREBRUM. 


199 


must  be  applied  with  caution  to  the  conditions  in  man.  As 
we  have  seen,  the  entire  cerebral  cortex  may  be  removed  from 
the  frog,  the  pigeon,  and  the  dog  without  causing  permanent 
paralysis,  although  in  the  animal 
last  named  there  is  at  first  a  more 
or  less  marked  loss  of  voluntary 
control.  In  man  and  the  anthro- 
poid apes  the  pyramidal  system  is 
more  highly  developed  and,  in  ac-  (J 
cordance  with  this  fact,  we  might 
expect  paralyses  resulting  from  le- 
sions of  the  motor  cortex  to  before 
permanent.  In  regard  to  man  it  is 
difficult  to  get  exact  data,  but  it  has 
been  stated,  on  the  basis  of  surgical 
operations,  that  the  paralysis  does 
not  pass  off  completely  with  time; 
there  remains  some  degree  of  pare- 
sis. The  more  complete  observa- 
tions made  on  the  anthropoids* 
indicate,  on  the  contrary,  that  after 
ablations  of  considerable  extent  in 
the  limb  areas  the  initial  paralysis 
soon  disappears  almost  completely, 
and  when  a  second  operation  is 
made  on  the  corresponding  area  in 
the  other  hemisphere,  there  is  no 
recrudescence  of  paresis  in  the  limb 
which  had  recovered  from  the  first 
operation.  The  way  in  which  this 
vicarious  substitution  is  effected  is 
not  definitely  known.  In  the  dog 
and  animals  still  lower  in  the  scale 
of  development  one  thinks  of  theru- 
brospinal  tract  and  its  connections 
with  the  basal  ganglion  of  the  cere- 
brum as  offering  a  mechanism,  in  addition  to  the  pyramidal  system, 
for  carrying  out  the  highly  co-ordinated  movements  of  locomotion, 
etc.,  but  the  exact  distribution  of  function  between  the  pyramidal 
(cortical)  and  the  subcortical  motor  systems  is  not  understood. 

The  Crossed  Control  of  the  Muscles  and  Bilateral  Represen- 
tation in  the  Cortex. — It  has  been  known  from  very  ancient  times 
that  an  injury  to  the  brain  on  one  side  is  accompanied  by  a  paral- 
ysis of  voluntary  movement  on  the  other  side  of  the  body,  a  condi- 
*  Leyton  and  Sherrington,  Loc.  tit. 


Fig.  89. — Schema  representing 
the  course  of  the  fibers  of  the  pyra- 
midal system:  1,  Fibers  to  the  nuclei  of 
the  cranial  nerve  ;  2,  uncrossed  fibers 
to  the  lateral  pyramidal  fasciculus ; 
3,  fibers  to  the  anterior  pyramidal 
fasciculus  crossing  in  the  cord ;  4  and 
5,  fibers  that  cross  in  the  pyramidal 
decussation  to  make  the  lateral 
pyramidal 'tract  of  the  opposite  side. 


200  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

tion  known  as  hemiplegia.  The  facts  given  above  regarding  the 
origin  and  course  of  the  pyramidal  system  of  fibers  explain  the 
crossed  character  of  the  paralysis  quite  satisfactorily.  The 
schema  thus  presented  to  us  is,  however,  not  entirely  without  ex- 
ception. In  cases  of  hemiplegia  in  which  the  whole  motor  area  of 
one  side  is  included  it  is  known  that  the  paralysis  on  the  other  side 
does  not  involve  all  the  muscles,  and,  in  the  second  place,  it  is 
said  that  there  is  some  muscular  weakness  on  the  same  side.  The 
paralysis  in  hemiplegia  affects  but  little,  if  at  all,  those  muscles 
of  the  trunk  which  are  accustomed  to  act  in  unison, — the  muscles 
of  inspiration,  for  instance,  the  diaphragm,  abdominal  and  inter- 
costal muscles,  and  the  muscles  of  the  larynx.  It  would  appear 
that  these  muscles  are  bilaterally  represented  in  the  cortex;  so 
that  if  one  side  of  the  brain  is  intact  the  muscles  of  both  sides  are 
still  under  voluntary  control;  or,  possibly,  these  more  or  less  auto- 
matic movements  may  be  under  the  control  of  subcortical  motor 
mechanisms  such  as  are  referred  to  in  the  preceding  paragraph. 

Are  the  Motor  Areas  Only  Motor  in  Function? — The  great 
number  of  nerve  cells  in  the  cortex  in  addition  to  the  large 
pyramidal  cells  that  give  origin  to  the  fibers  of  the  pyramidal 
system  makes  it  possible  histologically  that  other  functions  may 
be  mediated  in  the  same  region.  This  possibility  has  been  kept 
in  view  since  the  early  experiments  of  Munk,  in  which  he  showed 
that  lesions  in  the  Rolandic  region  are  followed  by  disturbances 
in  what  are  designated  as  the  body  sensations,  that  is,  in 
muscular  and  cutaneous  sensibility,  but  especially  the  former. 
It  was  suggested,  therefore,  at  one  time  that  one  and  the  same 
spot  in  the  cortex  might  serve  as  the  origin  of  the  motor  impulses 
to  a  given  muscle  and  as  the  cortical  termination  of  the  sensory 
impulses  coming  from  the  same  muscle,  the  reaction  in  con- 
sciousness, the  muscular  sensations,  being  mediated  perhaps 
through  cells  other  than  those  giving  rise  to  the  pyramidal  fibers. 
Recent  physiological  and  clinical  work  has,  however,  not  tended 
to  support  this  view.  The  motor  areas  appear  to  be  confined 
to  the  region  in  front  of  the  central  sulcus  of  Rolando,  while  the 
cortical  area,  in  which  the  afferent  fibers  mediating  body  sensibility 
(muscular-cutaneous)  make  their  final  termination  extends  back  of 
this  sulcus  in  the  posterior  central  convolution.  Whether, 
on  the  other  hand,  the  sense  areas  for  the  body  (cutaneous  and 
muscular)  extend  forward  into  the  cortex  of  the  frontal  lobe  is 
not  clearly  shown  by  experimental  or  clinical  evidence.  Flechsig, 
from  his  studies  upon  the  time  of  myelinization  of  the  afferent 
fibers  in  the  embryo  brain,  concludes  that  this  is  the  case,  and 
that,  therefore,  the  motor  and  sensory  areas  overlap  for  a  part 
at  least  of  their  extent  (see  p.  226  and  Fig.  98).  On  the  con- 


GENERAL  PHYSIOLOGY  OF  THE  CEREBRUM.        201 

trary,  in  an  interesting  report  by  Gushing*  of  two  cases  in  which 
the  anterior  central  convolution  was  stimulated  in  conscious 
patients,  it  is  stated  that  there  was  no  sensation  other  than  that 
arising  from  the  change  in  position  of  the  muscles  which  were 
thrown  into  contraction.  In  the  motor  area  there  are  numerous 
connections  by  association  tracts  with  other  parts  of  the  brain. 
By  this  means  the  motor  area,  without  doubt,  is  brought  into 
relation  with  many  other  parts  of  the  cortex,  and  the  sensations 
or  perceptions  aroused  elsewhere  may  react  upon  the  motor  paths. 
A  voluntary  movement,  however  simple  it  may  be,  is  a  psychologi- 
cal act  of  some  complexity,  that  is  to  say,  every  movement  is  pre- 
ceded or  accompanied  by  certain  sensations  and  perceptions  which 
depend  upon  sensory  stimulations  occurring  at  that  time,  or  upon 
experiences  derived  from  conditions  of  excitation  that  have 
occurred  at  some  previous  period — every  action  is  part  of  a 
train  of  conscious  or  subconscious  processes  whose  neural  mech- 
anism extends  over  wide  regions  of  the  cortex.  The  mental 
processes,  the  associations  that  lead  to  and  originate  the  motor 
discharge,  the  mental  image  of  the  movement  to  be  effected, 
cannot  be  definitely  located  in  the  cortex,  and  it  is  possible  that 
the  so-called  motor  area  itself  participates  in  these  psychical  ante- 
cedents. But  what  may  be  said  with  confidence  is  that  the  im- 
mediate origin  of  the  outgoing  motor  impulse  lies  in  the  area  along 
the  anterior  margin  of  the  central  sulcus  of  Rolando,  which  con- 
tains the  foci,  so  to  speak,  into  which  all  accessory  processes  are 
gathered,  so  far  as  they  affect  our  voluntary  muscular  acts,  and 
from  which  emerge  the  actual  efferent  stimuli  to  the  different 
muscles. 

*  Gushing,   "American   Journal   of   Physiology,"    1909    ("Proc.    Amer. 
Physiol.  Soc."). 


CHAPTER  X. 

THE  SENSE  AREAS  AND  THE  ASSOCIATION  AREAS  OF 
THE  CORTEX. 

The  delimitation  of  the  sensory  areas  in  the  cortex  is  a  matter 
of  very  considerable  difficulty,  owing  partly  to  the  fact   that   the 
determination  of  the  presence  or  absence  of  certain  states  of  con- 
sciousness in  the  animal  or  person  under  observation  cannot  be 
made  except  by  indirect  means,  and  partly  no  doubt  to  the  fact 
that  the  organization  of   the  sensory  mechanism   in  the  brain  is 
more  complex  and  diffuse  than  in  the  case  of  the  motor  apparatus. 
Moreover,  the  distinction  between  what  we  may  call  simple  sensa- 
tions and  the  more  complex    psychical   representations  and  judg- 
ments of  which  these  sensations  form  a  necessary  constituent  can- 
not be  made  clearly,  even  by  the  individual  in  whom  the  reactions 
occur.     We  recognize  in  ourselves  different  stages  in  the  degree  of 
consciousness    aroused    by    sensory    reactions.     Our    visual    and 
auditory  sensations  are  clearly    differentiated;  but  many  of  the 
lower  senses  escape  recognition  in  the  individual  himself,  since  the 
state  of  consciousness  accompanying    them  is  of  a  lower  order. 
Our  muscular  sensations,  for  instance,    are  so  indefinite  as  to  be 
practically  subconscious.     They  are  most  important  to  us  in  every 
act  of  our  lives,  yet  the  uninformed  person  is  unconscious  of  the 
existence  of  such  a  sensation,  and  if  deprived  of  it  would  recognize 
the  defect  only  in  the  consequent  loss  of  control  of  the  voluntary 
muscular  movements.     In  the  attempts  to  determine  in  what  part 
of  the  brain  the  various  sensations  are    mediated  every  possible 
method  of  inquiry  has  been  used  :  the   anatomical  course  of  the 
sensory  paths,  physiological  experiments  of  stimulation  and  ablation, 
and  observations  upon  individuals  with  pathological  or  traumatic 
lesions  in  the  brain.     The  results  of  these  investigations  are  pre- 
sented briefly  in  the  following  pages.     It  may  be  helpful  in  con- 
sidering these  results  to  bear  in  mind  the  fundamental  physiological 
conception  that  each  specialized  sense  is  supposed  to  have  its  own 
set  of  nerve  fibers.     These  fibers  after  entering  the  cord  in  the 
spinal  nerves,  or  the  brain  in  the  cranial  nerves,  are  assumed  to 
follow  different  intercentral  paths,  which  eventually  terminate  in 
the  cortex  of  the  cerebrum.     The  attempts  made  to  localize  these 
senses  in  the  cortex  reduce  themselves  practically  to  a  considera- 
tion of  the  location  of  the  termini  of  the  several  tracts.     Investi- 

202 


SENSE    AREAS    AND    ASSOCIATION    AREAS.  203 

gallons  made  so  far  indicate  that  these  termini  are  located  in 
different  regions,  and  that  destruction  of  any  terminus  has,  of 
course,  the  same  effect  upon  the  corresponding  sense  as  destruction 
of  the  tract  in  any  part  of  its  course.  If  we  go  beyond  this  point, 
and  endeavor  to  say  what  part  of  the  complex  mental  activity  asso- 
ciated with  each  kind  of  sensory  reaction  is  mediated  by  the  cells 
located  in  these  termini,  we  are  met  at  once  with  difficulties  which, 
at  present,  cannot  be  overcome.  Each  terminus  is  connected  by 
association  fibers  with  various  other  parts  of  the  cortex,  and  this 
whole  complex  of  neurons  is  concerned  no  doubt  in  the  psychical 
reactions  aroused. 

The  Body -sense  Area. — In  his  early  experiments  Munk 
insisted  that  lesions  of  the  cortex  involving  the  area  around  the 
central  sulcus  are  accompanied  by  a  state  of  anesthesfe  on  the 
other  side  of  the  body,  hemianesthesia,  particularly  as  regards 
the  tactile  and  muscular  sensations.  It  is  not  necessary,  perhaps, 
to  go  into  the  details  of  the  long  controversy  that  arose  in 
connection  with  this  point.  Both  the  clinical  and  the  experi- 
mental evidence  has  been  contradictory  in  the  hands  of  different 
observers,  but  the  tendency  of  recent  studies  has  been  to  show, 
as  stated  above,  that,  whereas  the  motor  areas  lie  anterior  to 
the  central  sulcus,  the  sensory  areas  concerned  with  the  cutaneous 
and  muscular  sensations  extend  posterior  to  this  sulcus.*  Posi- 
tive cases  are  recorded  in  which  lesions  involving  the  anterior 
central  convolutions  were  accompanied  by  paralysis  on  the 
other  side,  hemiplegia,  without  any  detectable  disturbance  of 
sensibility,  and,  on  the  other  hand,  lesions  have  been  described 
in  the  posterior  central  and  neighboring  parietal  convolutions 
in  which  there  was  a  hemianesthesia  more  or  less  distinctly 
marked  without  any  paralysis.  As  stated  above,  Gushing,  f 
in  his  report  upon  the  stimulation  of  the  cortex  in  two  conscious 
patients,  states  that  no  sensations  were  aroused  by  stimuli 
applied  to  the  anterior  central  convolution,  while  stimulation 
of  the  posterior  convolution  aroused  distinct  sensations  of 
numbness  and  of  touch.  Such  cases  tend  to  support  the  view 
that  the  motor  and  body  sense  areas,  although  contiguous,  do 
not  overlap.  Regarding  the  sensory  defects  associated  with 
lesions  of  the  parietal  lobe  posterior  to  the  central  sulcus  (pos- 
terior central  convolution,  supramarginal,  superior,  and  possibly 
inferior  parietal  convolutions),  it  seems  probable  that  they 
involve  chiefly  the  muscular  sense,  pressure  and  temperature 
sense,  and  the  judgments  or  perceptions  based  upon  these 
sensations,  while  the  sense  of  pain  is  affected  but  little,  if  at 
all.  Monakow  gives  the  order  in  which  sensory  defects  manifest 

*  Consult  von  Monakow,  "Ergebnisse  der  Physiol.,"  1902,  vol.  i,  part  i, 
p.  621.  t  Gushing,  loc/cit. 


204 


PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 


themselves  after  such  lesions,  as  follows :  The  localizing  and  muscle 
senses  are  chiefly  affected,  in  fact,  almost  lost  on  the  opposite  side; 
the  temperature  and  pressure  sense  may  be  affected,  while  the 
pain  sense  is  retained  or  but  slightly  affected.  The  clinicians  have 
observed  that  the  most  positive  and  invariable  symptom  of  lesions 
in  this  region  is  a  condition  of  astereognosis,  that  is,  a  diminution 
in  what  may  be  called  the  stereognostic  perceptions.  By  stereog- 
nostic  perception  is  meant  the  power  to  judge  concerning  the  form 
and  consistency  of  external  objects  when  handled,  and  it  must  be 
regarded  as  a  perception  based  upon  localized  sensations  of  touch, 

Central  Su Iocs 


eus  offuniculus 
-  cuneatos 


^Internal  arcuate  fibers 


of/oinal  Cord. 


Fig.  90. — Schema  representing  the  origin  and  course  of  the  fibers  of  the  median  fillet, — the 
intercentral  paths  of  the  fibers  of  body  sense. 

together  perhaps  with  those  of  temperature  and  muscular  sen- 
sibility. On  the  whole,  therefore,  we  must  infer  that  the  cortex  in 
this  postcentral  area  is  concerned  with  the  sensations  of  pressure, 
temperature,  and  muscular  conditions,  and  especially  the  higher 
type  of  these  sensations,  which  we  can  project  or  localize  accurately. 
This  conclusion  is  strengthened  by  the  fact  that,  as  described  in 


SENSE    AREAS    AND    ASSOCIATION    AREAS. 


205 


the  next  paragraph,  the  fibers  of  the  lemniscus  terminate  in  this 
same  region.  Secondly,  in  this  region  there  are  mediated  also 
possibly  some  of  the  syntheses  and  associations  of  these  sensations, 
which  we  designate  as  perceptions  or  judgments,  and  it  is  possible 
that  injuries  or  defects  here  may  be  followed  by  an  impairment  of 
these  higher  perceptive  reactions,  without  any  definite  loss  of  sen- 
sibility in  the  skin.  Such  a  defect  falls  under  the  general  head  of 
agnosia,  and  is  illustrated  by  the  condition  of  astereognosis  re- 
ferred to  above,  which  might  be  defined  as  chiefly  a  tactile  agnosia. 
The  part  of  the  cortex,  if  any,  in  which  the  tract  of  pain  fibers  makes 
its  final  terminus  has  not  been  definitely  localized. 

The  Histological  Evidence. — Course  of  the  "  Lemniscus." — 
On  the  histological  side  there  is  very  strong  corroborative  evi- 
dence for  the  view  that  cortical  centers  for  the  sensory  fibers 
of  the  skin  and  muscles  lie  in  the  parietal  lobe  in  the  region  in- 
dicated above.  This  evidence  is  connected  with  the  path  taken 


Fig.  91. — Cross-section  through  midbrain  (Kolliker)  to  show  the  position  of  the  lemniscus 
(L,  L):    Nr,  The  red  nucleus;  Sn,  the  substantia  nigra;  Fp,  the  peduncle. 

by  the  sensory  fibers  in  the  cord,  especially  those  of  the  pos- 
terior funiculi,  after  ending  in  the  nucleus  of  the  funiculus  gra- 
cilis  and  the  nucleus  of  the  funiculus  cuneatus  of  the  medulla. 
This  path  is  represented  in  a  schematic  way  in  the  accompanying 
diagram  (Fig.  90).  The  second  sensory  neurons  arise  in  the 
nuclei  mentioned.  For  the  most  part,  at  least,  these  new  neu- 
rons run  ventrally,  as  internal  arcuate  fibers,  cross  the  mid-line, 
and  then  pass  forward  or  anteriorly.  The  crossing  occurs  mainly 
just  in  front  of — that  is,  cephalad  to — the  pyramidal  decussa- 
tion,  forming  thus  a  sensory  decussation  (decussation  of  the 


206  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

lemniscus),  which  explains  the  crossed  sensory  control,  as  the 
pyramidal  decussation  explains  the  crossed  motor  control  of 
the  cerebrum  in  relation  to  the  body.  After  this  decussation 
the  sensory  fibers  form  a  longitudinal  bundle  on  each  side  known 
as  the  median  fillet  or  lemniscus,  which  in  the  pons  lies  just 
dorsal  to  the  pyramidal  system  of  fibers. 

The  lemniscus  fibers  may  be  traced  forward  (see  Fig.  91)  as 
far  as  the  superior  colliculus  of  the  corpora  quadrigemina  and 
the  thalamus,  the  important  termination  being  in  the  thalamus 
(ventral  or  lateral  nucleus).  Those  neurons  that  end  in  the 
thalamus  are  continued  forward  by  a  third  set  of  neurons,  which 
end  in  the  parietal  lobe  of  the  cerebrum  (see  Fig.  82,  C).  On  its 
way  through  the  medulla  and  pons  the  lemniscus  is  believed  to 
receive  accessions  of  sensory  fibers  from  the  sensory  nuclei  of 
the  cranial  nerves  of  the  opposite  side.  The  course  of  the  lem- 
niscus has  been  traced  by  various  means,  but  especially  by  the 
method  of  myelinization  during  embryonic  life  and  by  degenera- 
tion consequent  upon  long-standing  disuse.  As  was  stated  in 
the  section  upon  Nerve  Degeneration,  injury  to  an  axon  is 
followed  quickly  by  degeneration  of  the  peripheral  end,  and 
much  more  slowly  by  a  degeneration  of  the  central  end  and  the 
nerve  cell  itself,  when  the  path  is  not  again  established.  Certain 
long-standing  cystic  lesions  (porencephaly)  in  the  parietal  cor- 
tex have  resulted  in  an  atrophic  degeneration  of  the  lemniscus 
fibers,  thus  adding  materially  to  the  evidence  that  this  sensory 
tract  ends  eventually  in  the  region  indicated.*  Further  evidence 
of  the  same  character  is  found  in  the  observations  made  by 
Campbellf  upon  cases  of  tabes  dorsalis.  The  lesion  in  such  cases 
is  in  the  posterior  funiculi  of  the  spinal  cord,  but  eventually 
the  whole  upward  path  is  affected  and  degenerative  changes  are 
found  in  the  cells  of  the  posterior  central  convolution. 

From  the  connections  of  the  lemniscus  with  the  tracts  of  the 
posterior  funiculi  of  the  cord  it  is  evident  that  it  forms  one 
pathway  at  least  for  the  fibers  of  muscle  sense.  Whether  or  not 
the  fibers  of  pressure,  pain,  and  temperature  take  the  same  route 
is  not  known,  but  it  seems  probable,  at  least,  from  the  known 
connections  of  the  lemniscus  with  the  sensory  nuclei  of  the 
cranial  nerves  and  with  the  sensory  tracts  of  the  lateral  as  well 
as  the  posterior  funiculi  of  the  cord.  The  lemniscus  ends 
chiefly  in  the  thalamus,  before  passing  on  to  the  cortex,  and 
here,  as  in  other  similar  cases,  we  have  the  possibility  that  the 
lower  centers,  in  addition  to  the  reflex  connections  which  they 
make,  may  mediate  also  some  form  of  conscious  reaction. 
While  the  general  tendency  has  been  to  confine  the  conscious 

*H6sel,   "Archiv  f.  Psychiatric, "  24,  452,   1892. 

t  Campbell,  ' '  Histological  Studies  on  Localisation  of  Cerebral  Functions, " 
Cambridge,  1905. 


SENSE    AREAS    AND    ASSOCIATION    AREAS.  207 

quality  of  the  central  reactions  to  the  cortex,  there  is  no  proof 
that  the  lower  centers  are  entirely  lacking  in  this  property. 
In  Goltz's  dog  without  cerebral  cortex,  for  instance,  the  animal 
responded  to  various  sensory  stimuli,  and  when  hungry  gave 
evidence,  so  far  as  his  actions  were  concerned,  of  experiencing 
the  sensations  of  hunger;  but  whether  or  not  these  actions  were 
associated  with  conscious  sensations  is  hidden  from  us,  and  we  can 
hope  to  arrive  at  positive  conclusions  upon  this  point  only  by  obser- 
vations upon  man  himself. 

The  Center  for  Vision. — The  location  in  the  cortex  of  the 
general  area  for  vision  has  been  established  by  anatomical,  physio- 
logical, and  clinical  evidence.  The  physiologists  have  experimented 
chiefly  by  the  method  of  ablation.  Munk,  Ferrier,  and  later  ob- 
servers have  found  that  removal  of  both  occipital  lobes  is  followed 
by  defects  in  vision.  According  to  Munk,  removal  of  both  occip- 
ital lobes  is  followed  by  complete  loss  of  visual  sensations,  or,  as  he 
expresses  it,  by  cortical  blindness.  Goltz,  however,  contends  that 
in  the  dog  at  least  removal  of  the  entire  cerebral  cortex  leaves 
the  animal  with  some  degree  of  vision,  since  he  will  close  his  eyes 
if  a  strong  light  is  thrown  upon  them.  All  the  experiments  upon 
the  higher  mammals  (monkeys)  and  clinical  experience  upon  man 
tend,  however,  to  support  the  view  of  Munk.  Complete  removal 
of  the  occipital  lobes  is  followed  by  apparently  total  blindness. 
If  any  degree  of  vision  remains  it  is  not  sufficient  for  recogni- 
tion of  familiar  objects  or  for  directing  the  movements.  In  an 
animal  in  this  condition  the  pupil  is  constricted  when  light  is 
thrown  upon  the  eye;  but  this  reaction  we  may  regard  as  a  reflex 
through  the  midbrain,  and  there  is  no  reason  to  believe  that  it  is 
accompanied  by  a  visual  sensation.  When  the  injury  to  the  occip- 
ital cortex  is  unilateral  the  blindness  affects  symmetrical  halves  of 
the  two  eyes,  a  condition  known  as  hemiopia.  Destruction  of  the 
right  occipital  lobe  causes  blindness  in  the  two  right  halves  of  the 
eyes,  or,  in  accordance  with  the  law  of  projection  of  retinal  stimuli, 
in  the  two  left  halves  of  the  normal  visual  field  when  the  eyes 
are  fixed  upon  any  object.  Destruction  of  the  left  occipital  lobe 
is  followed  by  blindness  in  the  two  left  halves  of  the  retinas  or  the 
right  halves  of  the  visual  field.  This  result  of  physiological  ex- 
periments is  borne  out  by  clinical  experience.  Any  unilateral 
injury  to  the  occipital  lobes  is  followed  by  a  condition  of  hemiopia 
more  or  less  complete  according  to  the  extent  of  the  lesion.  Obser- 
vation, however,  has  shown  that  this  general  symmetrical  relation 
has  one  interesting  and  peculiar  exception.  The  most  important 
part  of  the  retina  in  vision  is  the  region  of  the  fovea  centralis, 
whose  projection  into  the  visual  field  constitutes  the  field  of  direct 
or  central  vision.  It  is  said  that  the  hemiopia  caused  by  unilateral 
lesions  of  the  cortex  does  not  involve  this  part  of  the  retina. 


208  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

The  Histological  Evidence. — The  histological  results  supple- 
ment in  a  very  satisfactory  way  the  findings  from  physiology  and 
pathology.  The  retina  itself,  considered  from  an  embryological 
standpoint,  is  an  outgrowth  from  the  brain  vesicles,  and  is  there- 
fore an  outlying  portion  of  the  central  nervous  system.  The  optic 
fibers,  in  terms  of  the  neuron  doctrine,  must  be  considered  as 
axons  of  the  nerve  cells  in  the  retina.  If,  therefore,  an  eye  is  enu- 
cleated or  an  optic  nerve  is  cut  the  fibers  connected  with  the 
brain  undergo  secondary  degeneration  and  their  course  can  be 
traced  microscopically  to  the  brain.  By  this  means  it  has  been 
shown  that  in  man  and  the  mammalia  there  is  a  partial  decus- 
sation  of  the  optic  fibers  in  the  chiasma.  The  fibers  from  the 
inner  side  of  each  retina  cross  at  this  point  to  the  opposite  optic 
tract;  those  from  the  outer  side  of  the  retina  do  not  decussate, 


Occipital  lobe. 


Occipito-thalamic  radiation. 
Superior  colliculus. 


Lateral  geniculate. 
Thalamus. 


Retina. 


Fig.  92. — Diagram  to  indicate  the  general  course  of  the  fibers  of  the  optic  nerves  and  the 
bilateral  connection  between  cortex  and  retina. 

but  pass  into  the  optic  tract  of  the  same  side.  The  fibers  of  the 
optic  tract  end  mainly  in  the  gray  matter  of  the  lateral  genicu- 
late body,  but  some  pass  also  to  the  thalamus  (pulvinar)  and 
some  to  the  superior  colliculus  of  the  corpora  quadrigemina. 


SENSE    AREAS   AND    ASSOCIATION    AREAS.  209 

These  locations,  therefore,  particularly  the  lateral  geniculates, 
must  be  considered  as  the  primary  optic  centers.  From 'these 
points  the  path  is  continued  toward  the  cortex  by  new  neurons 
whose  axons  constitute  a  special  bundle,  the  occipitothalamic 
radiation,  lying  in  the  occipital  part  of  the  internal  capsule 
(see  Fig.  82,  Z)).  A  schema  representing  this  course  of  the 
optic  fibers  is  given  in  the  accompanying  diagram  (Fig.  92). 
According  to  this  schema,  the  general  relations  of  each  occipital 
lobe  to  the  retinas  of  the  two  eyes  is  such  that  the  right  occip- 
ital cortex  represents  the  cortical  center  for  the  two  right  halves 
of  the  retinas,  while  the  left  occipital  lobe  is  the  center  for  the 
two  left  halves  of  each  retina, — a  relation  that  agrees  completely 
with  the  results  of  experimental  physiology  and  clinical  studies. 

In  addition  to  the  fibers  described,  which  may  be  regarded  as 
the  visual  fibers  proper,  there  are  other  fibers  in  the  optic  tracts 
and  optic  nerves  whose  physiological  value  is  not  entirely  clear. 
The  fibers  of  this  kind  that  have  been  described  are:  (1)  Inferior 
or  Gudden's  commissure.  Fibers  that  pass  from  one  optic  tract 
to  the  other  along  the  posterior  border  of  the  chiasma.  These 
fibers  form  a  commissural  band  connecting  the  two  internal 
(or  median)  geniculate  bodies,  and  possibly  also  the  inferior 
colliculi.  It  seems  probable  that  they  belong  to  the  central 
auditory  path  rather  than  to  the  visual  system.  (2)  Fibers 
passing  from  the  chiasma  into  the  floor  of  the  third  ventricle. 
The  further  course  of  these  fibers  is  not  clearly  known,  but  it  is 
possible  that  they  make  connections  with  the  nuclei  of  the  third 
nerve.  They  will  be  referred  to  in  the  section  on  Vision  in  con- 
nection with  the  light  reflex  of  the  iris.  (3)  A  superior  com- 
missure. Several  observers  have  claimed  that  there  is  a  com- 
missural band  along  the  anterior  margin  of  the  chiasma  which 
connects  one  optic  nerve  or  retina  with  the  other. 

There  are  many  points  in  connection  with  the  course  of  the 
optic  fibers  and  the  physiology  of  the  different  parts  of  the  occip- 
ital cortex  which  are  unknown  and  require  further  investigation. 
Some  of  these  points  may  be  referred  to  briefly. 

The  Amount  of  Decussation  in  the  Chiasma. — According 
to  the  schema  given  above,  half  of  the  fibers  in  each  optic  nerve 
decussate  in  the  chiasma.  There  is,  however,  no  positive  proof 
that  the  division  of  the  fibers  is  so  symmetrically  made.  In  the 
lower  vertebrates, — fishes,  amphibia,  reptiles,  and  most  birds — 
the  crossing  is  said  to  be  complete,  while  in  the  mammalia  a  certain 
proportion  of  the  fibers  remain  in  the  optic  tract  of  the  same  side. 
In  a  general  way,  it  would  appear  that  the  higher  the  animal  is 
in  the  scale  of  development  the  larger  is  the  number  of  fibers  that 
do  not  cross  in  the  chiasma.  At  least  it  is  true  that  a  larger  num- 
14 


210 


PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 


ber  remain  uncrossed  in  man  than  in  any  of  the  mammalia,  and  it  is 
also  possible  or  probable  that  the  extent  of  decussation  in  man 
shows  individual  differences.  There  seems  to  be  no  acceptable 
suggestion  regarding  the  physiological  value  of  this  partial  decus- 
sation other  than  that  of  a  probable  relation  to  binocular  vision.  It 
has  been  used  to  explain  the  physiological  fact  that  simultaneous 
stimulation  of  S3^mmetrical  points  in  the  two  retinas  gives  us  a 
single  visual  sensation. 

The  Projection  or  Localization  of  the  Retina  on  the 
Occipital  Cortex. — It  would  seem  most  probable  that  the  paths 
from  each  spot  in  the  retina  terminate  in  a  definite  region  of 
the  occipital  cortex,  and  attempts  have  been  made  by  various 
methods  to  determine  this  relation.  According  to  Henschen,*  the 


Fig.  93. — Perimeter  fields  in  quadrant  hemianopia.  The  outline  of  the  visual  fields 
is  given  by  the  dotted  lines.  Blindness  in  the  left  upper  quadrants;  cortical  lesion  in  and 
below  the  calcarine  fissure  (taken  from  Beevor  and  Collier). 

visual  paths  in  man  end  around  the  calcarine  fissure  on  the  mesial 
surface  of  the  brain,  and  this  portion  of  the  occipital  lobe  should 
be  regarded  as  the  true  cortical  terminus  of  the  optic  fibers. 
There  seems  to  be  much  evidence,  indeed,  that  the  immedi- 
ate ending  of  the  optic  paths  lies  in  this  region.  Thus, 
Donaldson  f  found,  upon  examination  of  the  brain  of  Laura 
Bridgman,  the  blind  deaf-mute,  that  the  cuneus  especially 
showed  marked  atrophy,  and  Flechsig,  J  by  means  of  the  myeliniza- 
tion  method,  arrived  at  the  conclusion  that  the  optic  fibers  end 
chiefly  along  the  margin  of  the  calcarine  fissure.  Clinical  cases 
are  frequently  quoted  in  which  lesions  of  the  region  of  the  calcarine 
fissure  were  followed  by  a  more  or  less  complete  hemiopia.  When, 
as  seems  to  be  the  most  common  occurrence,  such  lesions  occur 
above  the  fissure,  in  the  cuneus,  or  below  the  fissure,  in  the  gyrus 
lingualis,  the  resulting  hemiopia  is  confined  to  corresponding 

*  Henschen,  "Brain,"  1893,  170. 

t  Donaldson,  "American  Journal  of  Physiology,"  1892,  4. 

j  Flechsig,  "Localisation  der  geistigen  Vorgange,"  Leipzig,  1896. 


SENSE    AREAS    AND    ASSOCIATION    AREAS.  211 

quadrants  of  the  retina,  and  is  designated  frequently  as  quadrant 
hemiopia  (see  Fig.  93).  It  has  been  assumed  that  the  fibers  from 
the  fovea  end  perhaps  in  the  fissure  itself — according  to  some 
authors  (Henschen) ,  along  the  anterior  third  of  the  fissure,  according 
to  others  (Schmid  and  Laqueur*)  along  the  posterior  portion  of  the 
fissure.  Moreover,  since  unilateral  lesions  in  this  region,  however 
extensive,  do  not  cause  complete  blindness  in  the  fovea,  it  has 
been  supposed  that  this  important  part  of  the  retina  is  bilaterally 
represented  in  the  cortex,  so  that  complete  foveal  blindness — 
that  is,  blindness  of  the  centers  of  the  visual  fields — can  only 
occur  when  both  occipital  lobes  are  injured  in  the  region  of  the 
calcarine  fissure.  While  the  general  opinion  seems  to  be  that  this 
last-named  region  is  the  main  cortical  ending  of  the  retinal  fibers, 
especially  of  those  arising  from  the  foveal  area,  other  observers 
contend  that  the  entire  occipital  cortex,  lateral  as  well  as  mesial 
surfaces,  must  be  regarded  as  the  cortical  termination  of  the 
visual  paths,  and  that  even  the  foveal  portion  of  the  retina  is  con- 
nected with  a  wide  area  in  this  lobe.  Those  who  hold  this  view 
explain  the  known  fact  that  lesions  in  the  region  of  the  calcarine 
fissure  give  the  most  permanent  condition  of  hemiopia,  on  the 
view  that  these  lesions  involve  the  underlying  fibers  of  the 
occipitothalamic  radiation.  Monakow,f  for  instance,  points 
out  that  while  extensive  lesions  of  the  occipital  cortex  on  both 
sides  leave,  with  a  few  exceptions,  some  degree  of  central  vision, 
no  cases  are  reported  of  cortical  lesions  involving  only  or  mainly 
the  vision  in  the  macular  region.  He,  therefore,  argues  that 
while  the  paths  from  the  retina  to  the  lower  visual  centers 
(lateral  geniculate)  may  be  isolated,  the  further  connections 
with  the  cortex  must  be  widespread.  The  cortical  center  for 
distinct  vision  according  to  this  view  is  not  limited  to  a  narrow 
area,  but  must  involve  a  large  region  in  the  occipital  cortex. 
It  is  difficult  to  reconcile  this  view  with  the  ideas  of  isolated 
conduction  and  specific  function  of  each  part  of  the  cortex.  Some 
additional  facts  of  interest  have  been  obtained  from  experiments 
involving  the  stimulation  of  the  occipital  cortex.  Stimulation 
of  this  kind  causes  movements  of  the  eyes,  and  the  movements 
vary  with  the  place  stimulated,  t  Stimulation  of  the  upper  border 
of  the  lobe  causes  movements  of  the  eyes  downward,  stimulation 
of  the  lower  border  movements  upward,  and  of  intermediate  regions 
movements  to  the  side.  Assuming  that  the  direction  of  the  move- 
ment is  toward-that  part  of  the  visual  field  from  which  a  normal 
visual  stimulus  would  come,  it  is  evident  that  movements  of  the 

*  Schmid  and  Laqueur,  "Virchow's  Archiv,"  158,  1900. 

t  Monakow,  loc.  cit.,  also  "Ergebnisse  d.  Physiologic,"  1907. 

i  Schafer,  " Brain,"  11,  1,  1889,  and  13,  165,  1890. 


212  PHYSIOLOGY  <pF    CENTRAL   NERVOUS   SYSTEM. 

eyes  downward  would  imply  stimulation  of  the  upper  half  of  the 
retina,  since  objects  in  the  lower  part  of  the  visual  field  form  their 
image  on  the  upper  half  of  the  retina.  This  fact,  that  stimulation 
of  the  occipital  cortex  causes  definite  movements  of  the  eyeballs, 
seems  to  imply  that  there  are  efferent  fibers  in  the  occipitothal- 
amic  radiation  running  from  the  occipital  cortex  to  the  midbrain, 
where  they  make  connections  with  the  motor  nuclei  of  the  third, 
fourth,  and  sixth  cranial  nerves. 

The  Function  of  the  Lower  Visual  Centers. — The  first  ending 
of  the  optic  fibers  lies  in  the  lateral  geniculate  and  to  a  lesser 
extent  in  the  thalamus  and  superior  colliculus.  It  is  conceiv- 
able, of  course,  that  some  degree  of  visual  sensation  may  be 
mediated  through  these  centers.  Goltz  observed  that  in  dogs 
with  the  cerebrum  removed  the  animals  showed  a  constriction 
of  the  pupils  when  a  bright  light  was  thrown  upon  the  eyes  or 
even  closed  the  eyes.  It  is  the  general  belief  that  reactions  of 
this  kind  are  mechanical  or  unconditioned  reflexes  accompanied  by 
no  higher  psychical  reaction  than  in  the  case  of  spinal  reflexes. 
The  existence  in  the  midbrain  of  the  motor  nuclei  of  the  third  nerve* 
and  of  the  medial  longitudinal  fasciculus  through  which  con- 
nections are  established  with  the  motor  nuclei  of  other  cranial 
nerves,  furnishes  us  with  a  possible  reflex  arc  through  which  the 
visual  impulses  brought  into  the  lower  optic  centers,  especially 
the  superior  colliculus,  may  cause  co-ordinated  movements  of 
the  eyes  or  of  the  head.  Usually  it  is  assumed  that  conscious 
visual  sensations,  and  especially  visual  associations  and  mem- 
ories, are  aroused  only  after  the  impulses  reach  the  occipital 
cortex.  In  the  fishes  the  midbrain  forms  the  final  ending  of  the 
optic  fibers,  and  in  these  animals,  therefore,  whatever  psychical 
activity  accompanies  the  visual  processes  must  be  mediated 
through  this  portion  of  the  brain.  In  the  higher  animals,  how- 
ever, the  development  of  a  cerebral  cortex  is  followed  by  the 
evolution  of  the  occipitothalamic  radiation,  and  as  the  connec- 
tions of  the  occipital  cortex  increase  in  importance,  those  of  the 
midbrain  (with  the  optic  fibers)  dwindle  correspondingly.  Here, 
as  in  other  cases,  the  psychical  activity  is  concentrated  in  the  por- 
tions of  the  brain  lying  most  anteriorly,  and  doubtless  the  degree 
of  consciousness  is  greatly  intensified  in  the  higher  animals  in  cor- 
respondence with  the  development  of  the  cerebral  cortex,  whose 
striking  characteristic  is  its  capacity  to  evoke  a  psychical  reaction. 

The  Auditory  Center. — The  location  of  the  auditory  area  has 
been  investigated  along  lines  similar  to  those  used  for  the  visual 
center.  The  experimental  physiological  work  has  yielded  varying 
results  in  the  hands  of  different  observers.  Munk  and  Ferrier 
placed  the  cortical  center  for  hearing  in  the  temporal  lobe,  and 


SENSE    AREAS    AND    ASSOCIATION    AREAS. 


213 


in  spite  of  negative  results  by  Schafer  and  others  this  localization 
has  been  shown  to  be  substantially  correct.  Entire  ablation  of 
both  temporal  lobes  is  followed  by  complete  deafness.  Ablation 
on  one  side,  however,  is  followed  only  by  impairment  of  hearing, 
and  in  the  light  of  the  results  from  histology  and  from  the  clinical 
side  it  seems  probable  that  the  connections  of  the  auditory  cortex 
with  the  ear  follow  the  general  schema  of  the  optical  system  rather 
than  that  of  the  body  senses.  That  is,  it  is  probable  that  the 


Posterior  nucleus. 


Deiters's  nucleus. 

Dorsal  nucleus. 
Ventral  nucleus. 

Cochlear  branch. 


Vestibular  branch. 


Semicircular 
canals. 

Scar  pa's  ganglion. 
Cochlea. 
Spiral  ganglion. 
Fig.  94. — The  medullary  nuclei  of  the  eighth  nerve. — (From  Poireer  and  Charpy.) 

auditory  fibers  from  each  ear  end  partly  on  the  same  side  and 
partly  or  mainly  on  the  opposite  side  of  the  cerebrum.  The  exact 
portion  of  the  temporal  lobe  that  serves  as  the  cortical  terminus 
of  the  auditory  tract  of  fibers  cannot  be  determined  with  certainty, 
but  it  seems  probable  that  it  lies  mainly  in  the  superior  temporal 
gyrus  and  the  transverse  gyri  extending  from  this  into  the  lateral 
fissure  of  the  cerebrum  (fissure  of  Sylvius). 

The  Histological  Evidences. — On  the  histological  side  the  paths 
of  the  auditory  fibers  have  been  followed  with  a  large  measure  of 
success,  although  in  many  details  the  opinions  of  the  differ- 
ent investigators  vary  considerably.  The  eighth  cranial  nerve 


214 


PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 


springs  from  the  bulb  by  two  roots:  the  external  and  the 
internal.  The  former  has  been  shown  to  supply,  mainly  at 
least,  the  cochlear  portion  of  the  internal  ear,  and  is,  there- 
fore, the  auditory  nerve  proper.  This  division  is  spoken  of 
as  the  cochlear  branch.  The  internal  root  supplies  mainly 
the  vestibular  branch  of  the  internal  ear,  and  is,  therefore, 
spoken  of  as  the  vestibular  branch  (see  Fig.  94).  It  seems  cer- 
tain that  the  latter  is  not  an  auditory  nerve,  but  is  concerned 
with  peculiar  sensations  from  the  semicircular  canals  and  vestibule 
that  have  an  important  influence  on  muscular'  activity,  especially 
in  complex  movements.  The  central  course  of  these  two  roots  is 
quite  as  distinct  as  their  peripheral  distribution, — a  fact  that  bears 
out  the  supposition  that  they  mediate  different  functions.  The 
vestibular  branch  ends  in  the  nucleus  of  Deiters,  the  nucleus  of 
Bechterew,  and  the  nucleus  fastigii  of  the  cerebellum.  Through 
these  nuclei  reflex  connections  are  made  with  the  motor  centers 
of  the  cord  and  midbrain,  and  probably  also  with  the  cerebellum. 
The  path  is  not  known  to  be  continued  forward  to  the  cerebrum. 
The  central  course  of  the  cochlear  branch  is  indicated  schematically 

in  Figs.  94  and  95.  The 
fibers  constituting  this 
branch  arise  from  nerve 
cells  in  the  modiolus  of 
the  cochlea, — the  spiral 
ganglion.  These  cells, 
like  those  in  the  poste- 
rior root  ganglia,  are  bi- 
polar. One  axon  passes 
peripherally  to  end 
around  the  sense  cells 
of  the  cochlea,  at  which 
point  the  sound  waves 
arouse  the  nerve  im- 
pulses. The  other  axon 
passes  toward  the  pons, 
forming  one  of  the  fibers 
of  the  cochlear  branch. 
On  entering  the  pons 
these  cochlear  branches 
end  in  two  nuclei,  one 
lying  ventral  to  the  res- 
tiform  body  and  known 
as  the  ventral  or  acces- 
sory nucleus  (V.n.,  Fig. 

95),  and  one  dorsally,  known  as  the  dorsal  nucleus  or  the  tuber- 
culum  acusticum  (D.n.).  From  these  nuclei  the  path  is  continued 


if. 


Fig.  96. — Diagram  to  show  central  course  of 
auditory  fibers  (modified  from  Van  Gehuchten): 
D.n.,  Dorsal  nucleus  giving  rise  to  the  fibers  that 
form  the  medullary  strise  (a.s.);  V.n.,  the  ventral 
nucleus,  giving  origin  to  the  fibers  of  the  corpus 
trapezoideum  (c.tr.);  s.o.,  superior  olivary  nucleus; 
l.f.,  lateral  lemniscus;  n.s.,  nucleus  of  the  lateral 
lemniscus;  t.g.i.,,  the  inferior  colliculus. 


SENSE    AREAS    AND    ASSOCIATION    AREAS.  215 

by  secondary  sensory  neurons,  and  its  further  course  toward  the 
brain  is  still  a  matter  of  much  uncertainty  in  regard  to  many 
of  the  details.*  The  general  course  of  the  fibers,  however,  is 
known.  Those  axons  that  arise  from  the  accessory  nucleus  pass 
mainly  to  the  opposite  side  by  slightly  different  routes  (Fig.  95). 
Some  strike  directly  across  toward  the  ventral  side  of  the  pons, 
forming  a  conspicuous  band  of  transverse  fibers  that  has  long 
been  known  as  the  corpus  trapezoideum ;  others  pass  dorsally 
around  the  restiform  body  and  then  course  downward  through 
the  tegmental  region  to  enter  the  corpus  trapezoideum.  The 
fibers  of  this  cross  band  end,  according  to  some  observers,  in 
certain  nuclei  of  gray  matter  on  the  opposite  side  of  the  pons, 
especially  in  the  superior  olivary  body  and  the  trapezoidal 
nucleus,  and  thence  the  path  forward  is  continued  by  a  third 
neuron.  Certainly  from  the  level  of  the  superior  olivary  body 
the  auditory  fibers  enter  a  distinct  tract  long  known  to  the  anat- 
omist and  designated  as  the  lateral  fillet  or  lateral  lemniscus. 
Authors  differ  as  to  whether  the  auditory  fibers  of  this  tract  arise 
from  nerve  cells  in  the  superior  olivary  and  neighboring  nuclei, 
or  are  the  fibers  from  the  accessory  nucleus  which  pass  by  the 
superior  olivary  body  without  ending  and  then  bend  to  run  for- 
ward in  a  longitudinal  direction.  This  last  view  is  represented 
in  the  schema  (Fig.  95).  The  secondary  sensory  fibers  that 
arise  in  the  tuberculum  acusticum  pass  dorsally  and  then 
transversely,  forming  a  band  of  fibers  that  comes  so  near  to  the 
surface  of  the  floor  of  the  fourth  ventricle  as  to  form  a  structure 
visible  to  the  eye  and  known  as  the  medullary  or  auditory  striae. 
The  fibers  of  this  system  dip  inward  at  the  raphe,  cross  the 
mid-line,  and  a  part  of  them  at  least  eventually  reach  the  lateral 
lemniscus  of  the  other  side  either  with  or  without  ending  first 
around  the  cells  of  the  superior  olivary  nucleus.  According  to 
the  description  of  some  authors,  the  fibers  from  the  accessory 
nucleus  and  tuberculum  acusticum  do  not  all  cross  the  mid-line 
to  reach  the  lateral  lemniscus  of  the  other  side;  some  of  them 
pass  into  the  lateral  lemniscus  of  the  same  side;  so  that  the 
relations  of  the  fibers  of  the  cochlear  nerves  to  the  lateral  lemnis- 
cus resemble,  in  the  matter  of  crossing,  the  relations  of  the  optic 
fibers  to  the  optic  tract.  After  entering  the  lateral  lemniscus 
the  auditory  fibers  pass  forward  toward  the  midbrain  and  end 
in  part  in  the  gray  matter  of  the  inferior  colliculus  and  in  part  in 
the  median  or  internal  geniculate,  and,  according  to  Van  Gehuch- 
ten,  partly  also  in  a  small  mass  of  nerve  cells  in  the  midbrain  known 

*For  literature,  see  Van  Gehuchten,  "Le  Nevraxe,"  4,  253,  1903,  and 
8,  127,  1906. 


216  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

as  the  superior  nucleus  of  the  lemniscus.  From  this  second  or  third 
termination  another  set  of  fibers,  the  auditory  radiation,  continues 
forward  through  the  inferior  extremity  of  the  internal  capsule  to  end 
in  the  superior  temporal  gyrus  (see  Fig.  82,  E).  According  to 
Flechsig,*  who  has  studied  the  course  of  these  fibers  in  the 
embryo  by  the  myelinization  method,  the  main  group  passes 
from  the  median  geniculates  to  the  transverse  gyri  of  the  tem- 
poral lobe  within  the  lateral  fissure  of  the  cerebrum  (fissure 
of  Sylvius).  The  median  geniculates,  in  man  at  least,  have, 
therefore,  the  function  of  a  subordinate  auditory  center,  as  the 
lateral  geniculates  have  the  function  of  a  subordinate  visual 
center.  The  median  geniculates  are  connected  with  the  inferior 
colliculus,  and  also,  it  will  be  remembered,  with  each  other,  by 
commissural  fibers  (Gudden's  commissure)  that  pass  along  the 
optic  tracts  and  the  inferior  margin  of  the  chiasma.  The 
auditory  path,  therefore,  involves  the  following  structures: 
The  spiral  ganglion,  the  cochlear  nerve,  accessory  nucleus  and 
tuberculum  acusticum,  corpus  trapezoideum,  medullary  striae, 
superior  olivary,  lateral  lemniscus,  inferior  colliculus,  median 
geniculate,  Gudden's  commissure,  auditory  radiation,  and 
temporal  cortex. 

The  Motor  Responses  from  the  Auditory  Cortex. — According 
to  Ferrier,  stimulation  of  the  cortex  of  the  temporal  lobe  (inferior 
convolution)  causes  definite  movements,  such  as  pricking  of 
the  ears  and  turning  of  the  head  and  eyes  to  the  opposite  side. 
As  in  the  case  of  the  visual  area,  therefore,  we  must  suppose  that 
distinct  motor  paths  originate  in  the  auditory  region,  and  it  is 
natural  tc  suppose  that  these  paths  give  a  means  for  cortical  reflex 
movements  following  upon  auditory  stimulation. 

The  Olfactory  Center. — The  olfactory  sense  is  quite  un- 
equally developed  in  different  mammals.  Broca  divided  them  from 
this  standpoint  into  two  classes:  the  osmatic  and  the  anosmatic 
group,  the  latter  including  the  cetacea  (whale,  porpoise,  dolphin). 
The  osmatic  group  in  turn  has  been  divided  into  the  microsmatic 
and  macrosmatic  animals,  the  latter  class  including  those  animals 
in  which  the  sense  of  smell  is  highly  developed,  such  as  the  dog 
and  rabbit,  while  the  former  includes  those  animals,  such  as  man, 
in  which  this  sense  is  relatively  rudimentary,  f  The  peripheral  end- 
organ  of  smell  consists  of  the  olfactory  epithelium  in  the  upper 
portion  of  the  nasal  chambers.  The  physiology  of  this  organ  will 
be  considered  in  the  section  on  special  senses.  The  epithelial 
cells  of  which  it  consists  are  comparable  to  bipolar  ganglion 
cells.  The  processes  or  hairs  that  project  into  the  nasal  chamber 

*  Flechsig,  "  Localisation  der  geistigen  Vorgange,"  Leipzig,  1896. 

t  See  Barker,  "  The  Nervous  System,''  1899,  for  references  to  literature. 


SENSE    AREAS   AND    ASSOCIATION    AREAS 


217 


are  acted  upon  by  the  olfactory  stimuli,  and  the  impulses  thus 
aroused  are  conveyed  by  the  basal  processes  of  the  cells,  the  olfac- 
tory fibers,  through  the  cribriform  plate  of  the  ethmoid  bone  into 
the  olfactory  bulb. 

The  Olfactory  Bulb  and  its  Connections. — The  olfactory 
bulbs  are  outgrowths  from  and  portions  of  the  cerebral  hemi- 
spheres. Each  bulb  is  connected  with  the  cerebral  hemispheres 
by  its  olfactory  tract.  The  connections  established  by  the  fibers 


Fig.  96. — Diagram  of  the  central  course  of  the  olfactory  fibers:  /,  Olfactory  bulb} 
77,  olfactory  tract;  ///,  cortex  of  the  hippocampal  lobe  (gyrus  uncinatus) ;  IV,  anterior 
commissure,  olfactory  portion;  A,  olfactory  epithelial  cells  of  nose  (their  fibers,  olfactory 
nerve  fibers,  terminate  in  the  glomeruli  of  the  bulb) ;  B,  glomeruli  of  olfactory  bulb  where 
the  olfactory  fibers  come  in  contact  with  the  dendrites  of  the  mitral  cells;  C,  mitral  and 
brush  cells;  1,  2,  3,  axons  from  the  mitral  cells  constituting  the  fibers  of  the  olfactory 
tract.  Fibers  3,  which  enter  the  commissure,  arise,  according  to  some  observers,  from 
cells  in  the  olfactory  lobe  near  the  base  of  the  tract. 

of  this  tract  are  widespread,  complicated,  and  in  part  incom- 
pletely known.  All  those  portions  of  the  brain  connected  with  the 
sense  of  smell  are  sometimes  grouped  together  as  the  rhinenceph- 
alon.  According  to  von  Kolliker,  the  parts  included  under  this 
designation  are,  in  addition  to  the  olfactory  bulb  and  tract,  Am- 
mon's  horn,  the  fascia  dentata,  the  hippocampal  lobe,  the  f  ornix,  the 
septum  pellucidum,  and  the  anterior  commissure.  The  schematic 
connections  of  the  olfactory  fibers  are  as  follows  (Fig.  96) :  After 
entering  the  olfactory  lobe  the  fibers  terminate  in  certain  globular 
bodies,  the  glomeruli  olfactorii  (B), whose  diameter  varies  from  0.1  to 
0.3  mm.  Here  connections  are  made  by  contact  with  the  dendrites 


218  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

of  nerve  cells  of  the  olfactory  lobe,  the  mitral  and  brush  cells  (C). 
The  axons  of  these  cells  pass  toward  the  brain  in  the  olfactory  tract. 
Three  bundles  of  these  fibers  are  distinguished:  (1)  The  precommis- 
sural  bundle,  the  fibers  of  which  terminate  in  part  in  nerve  cells  sit- 
uated in  the  tract  itself,  but,  for  the  most  part,  enter  the  anterioi 
commissure  and  pass  to  the  same  or  the  opposite  side,  to  end  in  the 
hippocampal  lobes  or  other  gray  matter  belonging  to  the  rhinen- 
cephalon.  (2)  The  mesial  bundle,  the  fibers  of  which  terminate 
in  the  gray  matter  adjacent  to  the  base  of  the  olfactory  tract, 
the  tuberculum  olfactorium,  whence  the  path  is  probably  continued 
by  other  neurons  to  the  region  of  the  hippocampal  lobe.  (3)  The 
lateral  tract,  whose  fibers  seem  to  pass  to  the  hippocampal  lobe  of 
the  same  side.  According  to  Van  Gehuchten,*  none  of  the  fibers 
of  the  anterior  commissure  arise  from  the  nerve  cells  in  the  olfactory 
bulb.  He  considers  that  the  fibers  in  the  olfactory  portion  of  this 
commissure  constitute  an  association  system  connecting  the  olfac- 
tory lobe  of  one  side  with  the  olfactory  bulb  of  the  other  side. 

The  Cortical  Center  for  Smell. — So  far  as  the  histological 
evidence  goes,  it  tends  to  show  that  the  chief  cortical  termination 
of  the  olfactory  paths  is  found  in  the  hippocampal  convolution, 
especially  its  distal  portion,  the  uncus.  The  experimental  evi- 
dence from  the  side  of  physiology  points  in  the  same  direction. 
Ferrier  states  that  electrical  stimulation  in  this  region  is  followed 
by  a  torsion  of  the  lips  and  nostrils  of  the  same  side,  muscular 
movements  that  accompany  usually  strong  olfactory  sensations. 
On  the  other  hand,  ablations  of  these  regions  are  followed  by  de- 
fects in  the  sense  of  smell.  The  experimental  evidence  is  not  very 
satisfactory,  owing  to  the  technical  difficulties  in  operating  upon 
these  portions  of  the  brain  without  at  the  same  time  involving 
neighboring  regions.  There  is  some  clinical  evidence  also  that 
lesions  in  this  region  involve  the  sense  of  smell.  Thus  Carbonieri 
records  that  a  tumor  in  this  portion  of  the  temporal  lobe  occa- 
sioned epileptic  attacks  which  were  accompanied  by  nauseating 
odors. 

The  Cortical  Center  for  Taste  Sensations. — Practically 
nothing  definite  is  known  concerning  the  central  paths  and  cortical 
termination  of  the  taste  fibers.  The  course  of  these  fibers  in  the 
peripheral  nerves  has  been  much  investigated  and  the  facts  are 
mentioned  in  the  section  upon  "  special  senses."  It  is  usually 
assumed,  although  without  much  decisive  proof,  that  the  cortical 
center  lies  also  in  the  hippocampal  convolution  posterior  to  the 
area  of  olfaction.  Experimental  lesions  in  this  region,  according 
to  Ferrier,  are  accompanied  by  disturbances  of  the  sense  of  taste. 
On  embryological  grounds  Flechsig  supposes  that  the  cortical 
*  Van  Gehuchten,  "Le  Nevraxe,"  6,  191,  1904. 


SENSE    AREAS    AND    ASSOCIATION    AREAS.  219 

center  may  lie  in  the  posterior  portion  of  the  gyrus  fornicatus 
(6,  Fig.  99). 

Aphasia. — The  term  aphasia  means  literally  the  loss  of  the 
power  of  speech.  It  was  used  originally  to  indicate  the  condition  of 
those  who  from  accident  or  disease  affecting  the  brain  had  lost  in 
part  or  entirely  the  power  of  expressing  themselves  in  spoken  words, 
but  the  term  as  a  general  expression  is  now  extended  to  include  also 
those  who  are  unable  to  understand  spoken  or  written  language — 
that  is,  those  who  are  word-blind  or  word-deaf.  It  is  usual,  there- 
fore, to  distinguish  sensory  aphasia  from  motor  aphasia.  By  the 
latter  term  is  meant  the  condition  of  those  who  are  unable  to  speak, 
although  there  is  no  paralysis  of  the  muscles  of 'articulation, 
and  by  sensory  aphasia,  those  who  are  unable  to  understand  the 
written,  printed,  or  spoken  symbols  of  words,  although  there  is  no 
loss  of  the  sense  of  vision  or  of  hearing. 

Motor  Aphasia. — A  condition  of  motor  aphasia  not  infrequently 
results  from  injuries  to  the  head  or  from  hemorrhage  in  the  region 
of  the  middle  cerebral  artery.  The  first  exact  statement  of  the 
portion  of  the  brain  involved  seems  to  have  been  made  by  Bouil- 
laud  (1825),  who,  as  the  result  of  numerous  autopsies,  attributed 
the  defect  to  lesions  of  the  frontal  lobe. 


(It  is  a  curious  fact  that  Bouillaud's  observations  were  inspired  by  the  work 
of  Gall.  Gall  having  observed,  as  he  thought,  that  individuals  who  are  fluent 
speakers  or  who  have  retentive  memories  are  characterized  by  projecting  eyes, 
concluded  that  this  peculiarity  is  due  to  the  larger  size  of  the  lower  part  of  the 
frontal  lobe,  and  he  therefore  located  the  faculty  of  speech  in  this  region  of  the 
brain.  In  spite  of  the  vagaries  into  which  he  was  led  by  his  false  methods  Gall 
made  many  most  important  contributions  to  our  knowledge  of  the  anatomy  of 
the  brain  and  the  cord.  The  discovery  of  the  location  of  the  center  of  speech, 
however,  cannot  be  rightly  placed  to  his  credit,  since  his  reasons  for  its  location 
were,  so  far  as  we  know,  entirely  unjustified.  It  cannot  be  reckoned  as  more 
than  a  coincidence  that  in  this  particular  his  phrenological  localization  was 
afterward  in  a  measure  justified  by  facts.) 

The  essential  truth  of  Bouillaud's  observations  was  established 
by  other  observers,  and  Broca  located  the  part  of  the  brain  in- 
volved in  these  lesions  in  the  posterior  part  of  the  third  or  inferior 
frontal  convolution.  He  described  conditions  of  pure  motor 
aphasia,  designated  by  him  as  aphemia,  which  he  thought  were  due 
to  lesions  in  this  gyrus.  This  region  is,  therefore,  frequently 
known  as  Broca's  convolution  or  Broca's  center.  Subsequent  ob- 
servations have  tended  to  confirm  this  localization,  and  what 
is  designated  as  the  "  speech  center  "  has  been  placed  in  the 
inferior  frontal  convolution  in  the  gyrus  surrounding  the  anterior 
or  ascending  limb  of  the  lateral  fissure  (fissure  of  Sylvius,  S, 
Fig.  97).  Many  authors  insist  that  this  localization  is  too  limited, 
and  that  defects  in  the  power  of  speech  may  result  not  only  from 
injuries  to  this  region,  but  also  from  lesions  of  contiguous  areas, 


220  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

including  the  anterior  portion  of  the  island  and  the  opercular  por- 
tion of  the  central  convolution.  Autopsies  have  shown  that  in 
right-handed  persons  the  speech  center  is  placed  or  is  functional 
usually  in  the  left  cerebral  hemisphere,  while,  on  the  other  hand,  it 
is  stated,  although  hardly  demonstrated,  that  in  the  case  of  left- 
handed  individuals  aphasia  is  produced  by  lesions  involving 
the  right  side  of  the  brain.  This  region  is  not  the  direct  cor- 
tical motor  center  for  the  muscles  of  speech.  It  is  possible  that 
aphasia  may  exist  without  paralysis  of  these  latter  muscles.  It  is 
rather  the  memory  center  of  the  motor  innervations  necessary  to 
form  the  appropriate  sounds  or  words  with  which  we  have  learned 
to  express  certain  concepts.  The  child  is  taught  to  express  certain 
ideas  by  definite  words,  and  the  memory  apparatus  through  which 
these  associations  are  transmitted  to  the  motor  apparatus  may  be 
conceived  as  located  in  the  speech  center.  Lesions  of  any  kind 
affecting  this  area  will,  therefore,  destroy  more  or  less  the  ability 
to  use  appropriately  spoken  words,  and  clinical  experience  shows 
that  motor  aphasia  may  be  exhibited  in  all  degrees  of  complete- 
ness and  in  many  curious  varieties.  The  individual  may  retain 
the  power  to  use  a  limited  number  of  words,  with  which  he  ex- 
presses his  whole  range  of  ideas,  as,  for  instance,  in  the  case  de- 
scribed by  Broca,*  in  which  the  individual  retained  for  the  ex- 
pression of  numbers  only  the  word  "  three,"  and  was  obliged  to 
make  this  word  do  duty  for  all  numerical  concepts.  Other  cases 
are  recorded  in  which  the  patient  had  lost  only  the  power  to  use 
names — that  is,  nouns  ("  Marie  ") — or  could  remember  only  the 
initial  letters.  Others  still,  in  which  words  could  be  used  only 
when  associated  with  musical  memories,  as  in  singing;  or  in  which 
the  words  were  misused  or  employed  in  wrong  combinations 
(paraphasia) .  Motor  aphasias  have  been  classified  in  various 
ways  to  suit  the  different  schemata  which  have  been  invented  to 
explain  the  cerebral  mechanism  of  speech,  but  the  whole  subject 
is  in  reality  so  complex  that  most  of  these  classifications  must  be 
received  with  caution.  There  seems  to  be  no  doubt,  however,  that 
a  condition  of  what  may  be  called  pure  motor  aphasia  may  result 
from  localized  injuries  to  the  brain.  In  this  condition  there  is 
loss  of  the  power  of  articulate  speech,  without  paralysis  of  the 
muscles  of  articulation,  and  with  the  preservation  of  what  has  been 
called  internal  language,  that  is,  the  power  to  conceive  the  ideas  for 
which  the  appropriate  verbal  expressions  are  missing.  Most 
authors  conclude  that  this  condition  is  due  to  an  injury  or  lesion  in 
Broca's  convolution,  but  others  contend  that  the  evidence  for 

*  Exner,  "Hermann's  Handbuch  der  Physiologie,"  vol.  iii,  part  u,  p.  342. 
Consult  for  older  literature. 


SENSE    AREAS    AND    ASSOCIATION    AREAS.  221 

this  localization  is  at  present  unsatisfactory.*  It  does  not  seem 
to  be  certain  whether  or  not,  in  the  case  of  complete  lesion  of  the 
center  on  one  side,  the  ability  to  speak  can  be  again  acquired  by 
education  of  new  centers.  |  Some  recorded  cases  seem  to  indicate 
that  this  re-education  is  possible  in  the  young,  while  in  the  old  it 
is  more  difficult  or  impossible.  We  express  our  thoughts  not  only 
in  spoken,  but  also  in  written,  symbols.  As  this  latter  form  of 
expression  involves  a  different  set  of  muscles  and  a  different 
educational  experience,  it  is  natural  to  assume  that  the  complex 
associations  concerned  or,  to  use  a  convenient  expression,  the 
memory  centers,  should  involve  a  different  part  of  the  cortex.  It 
is,  in  fact,  observed  that  in  some  aphasics  the  loss  of  the  power  of 
writing,  a  condition  designated  as  agraphia,  is  the  characteristic 
defect,  rather  than  the  loss  of  the  ability  to  use  articulate  language. 
There  may  be  also,  as  a  result  of  cerebral  injury,  a  loss  of  the  power 
to  make  various  kinds  of  purposive  movements  or  combinations 
of  movements  other  than  those  used  in  speaking  or  writing,  and 
for  this  general  condition  the  term  "  apraxia  "  has  been  employed. 
Using  this  term  in  its  widest  sense,  pure  motor  aphasia  (aphemia) 
might  be  denned  as  an  apraxia  limited  to  the  muscles  of  articula- 
tion, and  agraphia  as  an  apraxia  involving  the  movements  of 
writing.  The  general  evidence  seems  to  show  that  these  conditions 
of  apraxia,  other  than  the  aphemia,  are  associated  with  lesions 
in  the  first  and  second  frontal  convolutions  anterior  to  the  motor 
area. 

Sensory  Aphasia. — In  sensory  aphasia {  the  individual  suffers 
from  an  inability  to  understand  spoken  or  written  language. 
Conditions  of  this  kind  have  been  referred  to  lesions  in  the  cortex 
of  the  temporal  or  temporo-parietal  region  (H  and  V,  Fig.  96), 
and,  as  in  the  case  of  motor  aphasia,  the  lesion  is  usually  on  the 
left  side.  Since  the  cortical  centers  for  hearing  and  seeing  are 
situated  in  distinct  parts  of  the  brain,  we  should  expect  that  the 
mechanism  for  the  association,  in  one  case  of  visual  memories  of 
verbal  symbols  with  certain  concepts,  and  in  the  other  case,  of 
auditory  memories,  should  also  be  located  in  separate  regions. 
Inability  to  understand  spoken  language,  or  word-deafness,  is,  in 
fact,  usually  attributed  to  a  lesion  involving  the  superior  or  middle 
temporal  convolution  contiguous  to  the  cortical  sense  of  hearing 
(H,  Fig.  97),  while  loss  of  power  to  understand  written  or  printed 
language,  word-blindness  (alexia),  is  traced  to  lesions  involving  the 

*  For  these  opposing  views  and  the  work  of  Marie  see  Moutier,  "L'  Aphasia 
de  Broca,"  Paris,  1908. 

t  See  Mills,  "Journal  of  the  Amer.  Med.  Assoc.,"  1904,  xliii. 

t  Consult  Starr,  "Aphasia,"  "Transactions  of  the  Congress  of  American 
Physicians  and  Surgeons,"  vol.  1,  p.  329,  1888;  also  Monakow,  "Gehirn- 
pathologie,"  1906;  Collier,  "Brain,"  1908. 


222 


PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 


s 


inferior  parietal  convolution,  the  gyrus  angularis,  contiguous  to 
the  occipital  visual  center  (V,  Fig.  97).  These  two  conditions 
may  occur  together,  but  cases  are  recorded  in  which  they  existed 
independently.  It  may  be  imagined  that  the  individual  suffering 
from  word-blindness  alone  is  essentially  in  the  condition  of  one 
who  attempts  to  read  a  foreign  language.  The  power  of  vision 
exists,  but  the  verbal  symbols  have  no  associations,  therefore  no 
meaning.  So  one  who  is  word-deaf  alone  may  be  compared  to  the 
normal  individual  who  is  spoken  to  in  a  foreign  tongue.  The  words 

are  heard,  but  they 
have  no  associations 
with  past  experience. 
Sensory  aphasia  may 
be  complete  or  incom- 
plete. In  the  com- 
plete form  there  is 
word-deafness  as  well 
as  word-blindness,  and 
there  may  be  difficul- 
ties as  well  in  the  pow- 
er of  articulate  speech. 
In  the  incomplete  type 
these  symptoms  are 
exhibited  in  milder 
and  varying  form. 
One  may  imagine  that 
our  ability  to  recog- 
nize external  objects 
through  the  senses 

might  be  affected  in  other  ways  than  a  failure  to  comprehend  the 
visual  or  auditory  symbols,  and  some  writers,  therefore,  employ  the 
wider  term  agnosia  to  indicate  any  failure  in  the  intellectual  recog- 
nition of  external  objects.  From  this  point  of  view  word-blindness 
might  be  designated  as  visual  agnosia,  word-deafness  as  auditory 
agnosia,  and  astereognosis  as  chiefly  a  tactile  agnosia.  The  exact 
localization  in  the  cortex  of  the  areas  involved  in  the  auditory  and 
visual  associations  and  perceptions  connected  with  speech  has  not 
been  established  definitely.  The  question  is  a  complex  and  difficult 
one,  and  those  who  have  had  the  most  experience  are  perhaps  the 
most  cautious  in  referring  word-blindness  or  word-deafness  to  the 
lesion  of  circumscribed  areas  of  the  cortex.*  It  may  be  said, 
however,  with  some  certainty,  that  the  phenomena  of  sensory 
aphasia  in  general  are  connected  with  lesions  involving  the  area 

*  For  a  general  review  see  Monakow,  "Ergebnisse  der  Physiologic,"  1907, 
p.  334. 


H 


Fig.  97. — Lateral  view  of  a  human  hemisphere;  cor- 
tical area  V,  damage  to  which  produces  "mind-blind- 
ness" (word-blindness);  cortical  area  H,  damage  to  which 
produces  "mind-deafness"  (word-deafness);  cortical  area 
S,  damage  to  which  causes  the  loss  of  articulate  speech; 
cortical  area  W,  damage  to  which  abolishes  the  power  of 
writing. — (Donaldson . ) 


SENSE    AREAS    AND    ASSOCIATION    AREAS.  223 

along  the  margins  of  the  posterior  portion  of  the  lateral  fissure 
(fissure  of  Sylvius),  and  extending  into  the  parietal  lobe  as  far  as 
the  angular  gyms,  and  with  the  cortex  within  the  fissure  including 
the  cortex  of  the  island. 

The  general  facts  regarding  aphasia  illustrate  very  well  the 
theory  or  idea  usually  held  among  physiologists  in  regard  to  the  dis- 
tribution or  localization  of  mental  activity  in  the  cerebral  cortex. 
The  understanding  and  the  use  of  spoken  or  written  language  is,  so 
to  speak,  a  mental  whole,  both  from  the  standpoint  of  education 
and  of  use.  To  understand  or  to  express  certain  conceptions  im- 
plies the  use  of  definite  words,  and  our  visual,  auditory,  and  motor 
experiences  are  combined  in  these  symbols.  Each  phase  of  this  com- 
plex may  be  cultivated  more  or  less  separately;  in  the  case  of  the 
unlettered  man,  for  instance,  the  written  or  printed  symbols  form 
no  part  in  the  associations  connected  with  his  verbal  concepts.  Cor- 
responding to  these  facts  we  have,  on  the  anatomical  side,  a  portion 
of  the  brain  in  which  the  auditory  memories  are  organized, — that 
is,  they  are  connected  in  some  way  with  a  definite  arrangement 
of  nerve  cells  and  their  processes,  another  part  in  which  the 
visual  memories  are  organized,  and  other  parts  in  which  the 
motor  memories  as  regards  speaking  or  writing  are  laid  down 
in  some  definite  form.  Each  part  is  a  distinct  center,  but 
their  combined  use  in  intellectual  life  would  imply  that  they 
are  connected  by  association  fibers,  so  that,  although  fun- 
damentally distinct,  they  are  practically  combined  in  their 
activity.  Corresponding  with  this  conception  it  is  found  from 
clinical  experience  that  sensory  aphasics  suffer  a  deterioration, 
more  or  less  pronounced,  of  their  general  intellectual  capacity 
according  to  the  extent  of  the  area  involved.  We  may  believe 
that  the  varying  gifts  of  individuals,  in  the  matter  of  the  use  of 
language,  rest  partly  on  the  amount  of  training  received  and 
partly  on  the  inborn  character  and  completeness  of  the  nervous 
machinery  in  the  different  centers. 

The  Association  Areas. — According  to  the  views  presented 
above,  it  will  be  seen  that  the  motor  and  sense  areas  occupy  only 
a  small  portion  of  the  cortex,  forming  islands,  as  has  been  said, 
surrounded  by  much  larger  areas.  Flechsig*  has  designated  these 
latter  areas  as  association  areas,  and  has  advocated  the  view  that 
they  are  the  portions  of  the  cortex  in  which  the  higher  and  more 
complex  mental  activities  are  mediated,  the  true  organs  of  thought. 
His  views  as  to  the  relations  and  physiological  significance  of  these 
areas  have  been  based  chiefly  on  the  study  of  the  embryo  brain 
with  reference  to  the  time  of  acquisition  of  the  myelin  sheaths. 

*  Flechsig,  "Gehirn  und  Seele,"  Leipzig,  1896;  also,  "Archives  de  Neurol- 
ogic," vol.  ii,  1900. 


224  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

Thus  he  finds  that  the  fibers  to  the  sense  areas  acquire  their  myelin, 
and  therefore  according  to  his  view  become  fully  functional  before 
those  distributed  to  the  association  areas.  Moreover,  in  the  em- 
bryo, at  least,  these  latter  areas  are  not  supplied  with  projection 
fibers, — that  is,  they  are  not  connected  directly  with  the  under- 
lying parts  of  the  nervous  systems.  Their  connections  are  with 
each  other  and  with  the  various  sense  centers  and  motor  centers 
of  the  cortex. 

The  association  areas  may  be  regarded  therefore  as  the  regions 
in  which  the  different  sense  impressions  are  synthesized  into  complex 
perceptions  or  concepts.  The  foundations  of  all  knowledge  are 
to  be  found  in  the  sensations  aroused  through  the  various  sense 
organs;  through  these  avenues  alone  can  our  consciousness  come 
into  relaticn  with  the  external  or  the  internal  (somatic)  world, 
and  the  union  of  these  sense  impressions  into  organized  knowledge 
is,  according  to  Flechsig,  the  general  function  of  the  association 
areas.  This  function  of  the  association  areas  is  indicated  by  the 
anatomical  fact  that  they  are  connected  with  the  various  sense 
centers  by  tracts  of  association  fibers,  suggesting  thus  a  mechanism 
by  which  the  sense  qualities  from  these  separate  sense  centers  may 
be  combined  in  consciousness  to  form  a  mental  image  of  a  complex 
nature.  The  sequence  of  phenomena  in  the  external  world  is  or- 
derly, and,  corresponding  to  this  fact,  the  reflection  of  these  phenom- 
ena in  the  sequence  and  combinations  of  sensations  is  also  orderly. 
In  the  association  areas  our  memory  records  of  past  experiences 
and  their  connections  are  laid  down  in  some,  as  yet  unknown, 
material  change  in  the  network  of  nerve  cells  and  fibers.  Here, 
as  elsewhere  in  the  nervous  system,  it  may  be  supposed  that  the 
efficiency  of  the  nervous  machinery  is  conditioned  partly  by  the 
completeness  and  character  of  training,  but  largely  also  by  the 
inborn  character  of  the  machinery  itself.  The  very  marked  differ- 
ences among  intelligent  and  cultivated  persons — for  instance,  in 
trie  matter  of  musical  memory  and  the  power  of  appreciating  and 
reproducing  musical  harmonies — cannot  be  attributed  to  differences 
in  training  alone.  The  gifted  person  in  this  respect  is  one  who  is 
born  with  a  certain  portion  of  his  brain  more  highly  organized  than 
that  of  most  of  his  fellow-men.  This  general  conception  that  the 
special  capacities  of  talented  individuals  rest  chiefly  upon  inborn 
differences  in  structure  or  organization  of  the  brain  may  be  re- 
garded as  one  outcome  of  the  modern  doctrine  of  localization  of 
functions  in  this  organ.  In  the  beginning  of  the  nineteenth  century 
it  seems  to  have  been  the  general  view  that  those  who  had  a  high 
degree  of  mental  capacity  might  direct  their  activity  with  equal 
success  in  any  direction  according  to  the  training  received.  A  man 
who  could  walk  fifty  miles  to  the  north,  it  was  said,  could  just  as 


SENSE    AREAS    AND    ASSOCIATION    AREAS.  225 

easily  walk  fifty  miles  to  the  south,  and  a  man  whose  training 
made  him  an  eminent  mathematician  might  with  different  training 
have  made  an  equally  eminent  soldier  or  statesman.  In  our  day, 
however,  with  our  ideas  of  the  organization  of  the  brain  cortex, 
and  our  belief  that  different  parts  of  this  cortex  may  give  different 
reactions  in  consciousness,  it  seems  to  follow  that  special  talents 
are  due  to  differences  in  organization  of  special  parts  of  the 
cortex. 

Subdivision  of  the  Association  Areas. — On  anatomical  grounds 
Flechsig  distinguishes  three  (or  four)  association  areas :  The  frontal 
or  anterior  35,  Fig.  100),  which  lies  in  front  of  the  motor  area; 
the  median  or  insular, — that  is,  the  cortex  of  the  island  of  Reil; 
and  the  posterior,  which  lies  back  of  the  body  feeling  area,  extending 
to  the  occipital  lobe  and  also  laterally  into  the  temporal  lobe. 
This  area  Flechsig  suggests  may  be  subdivided  into  a  parietal  area, 
34,  Fig.  100,  and  a  temporal  area,  36,  Fig.  100.  The  greater  rela- 
tive development  of  these  areas  is  one  of  the  features  distinguishing 
the  human  brain  from  those  of  the  lower  mammals.  In  accordance 
with  the  general  conception  of  localization  of  functions  Flechsig 
suggests  that  these  areas  have  different  functions, — that  is,  take 
different  parts  in  the  complex  of  mental  activity.  Basing  his 
views  upon  the  nature  of  the  association  tracts  connecting 
them  with  the  sense  centers,  he  suggests  that  the  posterior  area 
is  concerned  particularly  in  the  organization  of  the  experiences 
founded  upon  visual  and  auditory  sensations,  and  shows  especial 
development  in  cases  of  talents,  such  as  those  of  the  musician, 
which  rest  upon  these  experiences.  The  anterior  area,  being  in 
closer  connection  with  the  body  sense  area,  may  possibly  be  espe- 
cially concerned  in  the  organization  of  experiences  based  upon  the 
internal  sensations  (bodily  appetites  and  desires),  and  in  al- 
terations or  defective  development  of  this  portion  of  the  brain 
may  lie  the  physical  explanation  of  mental  and  moral  degen- 
eracy. This  general  idea  is  borne  out  in  a  measure  by  histo- 
logical  studies  of  the  brains  of  those  who  are  mentally  deficient 
(amentia)  or  mentally  deranged  (dementia).  It  is  stated*  that 
the  brain  in  such  cases  shows  a  distinct  thinning  of  the  cortex  and 
that  the  maximum  focus  of  this  change  is  found  in  the  prefrontal 
lobes  (anterior  association  area).  In  the  case  of  the  idiotic  this 
area  is  distinctly  undeveloped  and  in  the  insane  the  atrophy  is 
marked  in  proportion  to  the  degree  of  dementia.  Regarding  the 
peculiar  functions  of  the  cortex  of  the  island  of  Reil  there  are 
no  facts  sufficiently  distinct  to  warrant  a  positive  statement, 
although,  as  stated  above,  the  data  from  pathological  anatomy 

*  Bolton,  "Brain,"  1903,  p.  215,  and  1910,  p.  26. 
15 


226  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

would  seem  to  indicate  that  this  portion  of  the  cortex  may  form 
a  part  of  the  speech  area  both  on  the  motor  and  the  sensory  side. 
The  area  is  much  more  developed  in  man  than  in  the  lower  mam- 
mals, and  its  connections  with  other  parts  of  the  cortex  by  means 
of  association  tracts  are  such  as  to  lead  to  the  supposition  that  its 
general  functions  are  of  the  higher  synthetic  character  attributed 
to  the  association  areas  in  general. 

By  way  of  caution  it  should  be  stated  that  the  general  ideas  developed 
above  in  accordance  with]Flechsig's  views  do  not  meet  with  universal  accept- 
ance. Some  of  the  most  experienced  observers  are  unwilling  to  admit  that 
such  a  degree  of  localization  of  the  psychical  activities  really  exists.  They 
contend  that  the  whole  cortex  may  be  concerned  in  mediating  the  highest 
mental  processes,  and  quote  post-mortem  examinations  of  carefully  studied 
cases  in  support  of  this  view.  Even  in  the  primary  sense  centers  or  motor 
centers  the  character  of  the  lamination  of  the  cortex  indicates  the  possibility 
that  the  higher  synthetic  functions  may  be  mediated  there  in  addition  to  the 
reception  of  sensory  impulses  or  the  generation  of  motor  impulses.  We 
must  recognize,  in  fact,  that  the  schemata  designed  to  show  the  distribution  of 
the  higher  psychical  activities  in  the  cortex  represent  at  present  only  hypotheses 
which  need  confirmation  before  they  can  be  finally  accepted.  We  may  feel 
considerable  confidence  in  the  localizations  of  the  motor  areas,  and  of  some,  at 
least,  of  the  sensory  areas,  but  in  the  matter  of  the  more  complex  mental 
acts,  failure  in  which  expresses  itself  hi  the  conditions  of  aphasia,  dementia, 
perversions,  etc.,  our  knowledge  is  incomplete,  both  as  regards  analysis  of  the 
symptoms  and  the  localities  affected  in  the  brain. 

The  Development  of  the  Cortical  Area. — Flechsig*  has 
published  the  results  of  an  extensive  study  of  the  time  of  mye- 
linization  of  the  fibers  in  the  cerebrum  of  man  from  the  fourth 
month  of  intra-uterine  to  the  fourth  month  of  extra-uterine  life. 
The  first  areas  to  develop  in  the  cortex  are  the  primary  sense 
centers  (smell,  cutaneous  and  muscle  sense,  sight,  hearing,  and 
touch),  and  later  in  connection  with  these  centers  systems  of  motor 
fibers  appear.  There  are  thus  formed  seven  primary  zones,  sensory 
and  motor,  to  which  he  gives  the  name  of  projection  areas.  The 
location  of  these  areas  is  shown  in  part  in  Figs.  98  and  99,  2  ($,  &\ 
5,  6,  7  (7b),  8,  15.  Two  areas  connected  with  the  olfactory  sense 
are  not  shown  in  these  figures;  they  appear  in  the  anterior  per- 
forate lamina  on  the  base  of  the  brain  and  in  the  uncinate  gyrus. 
Later  there  is  developed  around  these  primary  zones  areas  that 
Flechsig  calls  marginal  or  border  zones,  which  have  no  projection 
fibers,  but  which  are  connected  by  short  association  fibers  with 
one  or  more  of  the  primary  projection  zones,  14,  16  to  33,  in  Figs. 
100  and  101.  Later  still  the  great  association  areas — S4,  35,  36, 
Figs.  100  and  101 — acquire  their  myelinated  fibers.  These  latter 
centers,  as  indicated  above,  may  be  considered  as  association  areas 

*  Flechsig,  "Berichte  der  mathematisch-physischen  Klasse  der  konigl. 
Sachs.  Gesellschaft  der  Wissenschaften  zu  Leipzig,"  1904.  For  a  summary  of 
the  results  of  this  work  see  Sabin,  "The  Johns  Hopkins  Hospital  Bulletin,'* 
February,  1905. 


SENSE   AREAS   AND   ASSOCIATION   AREAS. 


227 


Fig.  98.— Lateral  surface  of  the  brain,  showing  the  primordial  areas,  both  sensory  and 
automatic,  in  dotted  zones.— (Flechsig.) 


Fig.  99.— Same  zones  on  the  mesial  surface  of  the  brain.—  (Flechsig). 


228 


PHYSIOLOGY   OF   CENTRAL   NERVOUS   SYSTEM. 


Fig.  100. — Lateral    surfaces    of    the   brain,  showing   the  primordial  and    marginal  zones. 


W^fe 


ii 


Fig.  101.— Same  areas  on  the  mesial  surface.— (Flechsig.} 


SENSE    AREAS    AND    ASSOCIATION    AREAS.  229 

with  more  complex  connections,  and  they  serve  to  mediate,  pos- 
sibly, the  higher  psychical  activities.  Flechsig,  in  his  report, 
designates  these  areas  from  an  anatomical  point  of  view  as  terminal 
or  central  zones.  As  the  result  of  his  histological  work,  as  far 
as  it  has  progressed,  he  distinguishes  thirty-six  areas  in  the  cortex 
in  which  the  myelinization  of  the  fibers  occurs  separately,  and  in 
which,  therefore,  by  inference  different  physiological  activities 
are  mediated.  These  thirty-six  areas  are  subdivided  as  follows: 
L  Primary  areas. 

la.  Primary  projection  areas  (1,  2,  4,  5,  6,  7,  8  (15),  seven  or 
eight  in  number,  and  provided  with  projection  fibers — 
sensory  and  motor. 

I&.  Primary  areas  without  projection  fibers  (3, 9,  10, 11,  IS,  13) 
and  apparently  without  association  fibers.     Functions  un- 
certain. 
II.  Association  areas. 

II^  Intermediate  or  border  areas,  14,  16-33,  provided  with 

short  association  fibers. 

II6*  Terminal  or  central  areas,  34,  35,  36,  provided  with  long 
association  fibers. 

Histological  Differentiation  in  Cortical  Structure. — While 
the  general  structure  of  the  cortex  is  everywhere  similar,  detailed 
examination  has  shown  differences  in  the  shape  of  the  cells,  the 
thickness  and  number  of  the  strata  or  laminae,  the  calibre  of  the 
fibers,  etc.,  which  are  said  to  be  constant  for  any  given  region.  By 
this  means  it  is  possible  to  divide  the  cerebral  cortex  into  a  number 
of  areas  whose  structures  are  sufficiently  distinct  to  be  recognized 
with  some  certainty.  Reasoning  from  analogy,  we  should  infer 
that  a  differentiation  in  structure  implies  a  subdivision  of  physio- 
logical activity,  and  to  this  extent  this  recent  histological  work 
supports  the  view  of  a  localized  distribution  of  function  in  the 
cortex.  Campbell,*  in  a  very  thorough  investigation  of  this  kind, 
has  succeeded  in  separating  some  fifteen  or  sixteen  different  areas, 
and  the  results  obtained  by  him  support  in  a  general  way  the  local- 
izations described  in  the  preceding  pages.  Thus  the  cortex  in  the 
postcentral  convolution  (body-sense  area)  has  a  structure  dis- 
tinctly different  from  that  of  the  precentral  convolution  (motor 
area),  the  latter  being  characterized  among  other  things  by  the 
presence  of  giant  pyramidal  cells  (Betz  cells),  and  a  marked  dimi- 
nution in  the  width  of  the  granular  layer  of  cells.  In  the  occipital 
lobes  the  region  round  the  calcarine  fissure  has  a  structure  differ- 
ent from  that  of  the  contiguous  cortex,  and  a  similar  difference  is 
claimed  for  the  auditory  region.  Campbell  believes  that  the  ex- 
treme end  of  the  frontal  lobe  (prefrontal  region)  has  a  compara- 

*  Campbell,  "Histological  Studies  on  Localisation  of  Cerebral  Functions," 
Cambridge,  1905;  See  also  Brodmann,  "Journal  f.  Psychol.  u.  NeuroL," 
1902,  7. 


230  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

tively  undeveloped  structure,  but  Bolton,*  on  the  contrary,  states 
that  it  has  a  typical  structure  and  believes  that  it  plays  a  part  of 
the  greatest  importance  in  the  higher  or  general  processes  of  as- 
sociation. It  is  the  last  region  of  the  cortex  to  be  evolved.  In 
mental  decadence  or  dementia  it  is,  according  to  this  author,  the 
first  region  to  undergo  dissolution,  and  in  conditions  of  amentia  it 
is  undeveloped. 


Fig.  102. — Diagram  to  show  the  composition  of  the  corpus  callosum  as  a  system  of  oom- 
missural  fibers,  without  projection  fibers. — (Cajal.) 

The  Corpus  Callosum. — The  corpus  callosum  is  the  most 
conspicuous  of  the  bands  of  commissural  fibers  that  connect  one 
cerebral  hemisphere  with  the  other.  Similar  tracts  of  the  same 
general  nature  are  the  anterior  commissure  and  the  fornix. 
The  position  and  great  development  of  the  corpus  callosum 
has  made  it  the  object  of  experimental  as  well  as  anatomical 
investigation.  When  the  corpus  is  divided  by  a  section  along  the. 
longitudinal  fissure  (v.  Koranyi)  no  perceptible  effect  of  either  a 
motor  or  sensory  nature  is  observed  in  the  animal.  When  it  is 
stimulated  electrically  (Mott  and  Schafer)  from  above,  symmetri- 
cal movements  on  the  two  sides  of  the  body  may  be  obtained.  If 
the  motor  cortex  on  one  side  is  removed,  stimulation  in  the  lon- 
gitudinal fissure  causes  movements  only  on  the  side  controlled 
by  the  uninjured  cortex.  These  facts  are  in  harmony  with  the 
results  of  histological  studies,  which  indicate  that  the  fibers  of  the 
corpus  callosum  do  not  enter  directly  into  the  internal  capsules, 
to  be  distributed  to  underlying  portions  of  the  brain,  but  are  truly 
commissural  and  connect  portions  of  the  cortex  of  one  hemisphere 
with  the  cortex  of  the  other  side.  This  relation  is  indicated  in  the 
*  Bolton,  "Brain,"  1910,  p.  26. 


SENSE    AREAS    AND    ASSOCIATION    AREAS.  231 

accompanying  diagram  (Fig.  102).  So  far  as  the  motor  regions  are 
concerned,  there  is  some  evidence  that  the  connection  thus  es- 
tablished is  between  symmetrical  parts  of  the  cortex  (Muratoff) , — 
that  is,  between  parts  having  similar  functions, — and  we  may 
regard  the  corpus  as  a  means  by  which  the  functional  activities 
of  the  two  sides  of  the  cerebrum  are  associated.  On  the  human 
side,  study  of  cases  of  lesions  of  the  corpus  callosum  has  yielded  an 
important  suggestion  in  line  with  the  conclusion  just  stated. 
Liepmann*  has  reported  cases  of  this  kind  in  which  there  were 
apraxic  symptoms  (dyspraxia)  in  the  movements  of  the  left  side 
of  the  body,  although  the  right  cortex  was  uninjured.  He  draws 
the  conclusion  that  in  movement  complexes  in  general  the  left 
hemisphere  leads  or  initiates,  as  in  the  case  of  articulate  speech, 
and  that  through  the  commissural  fibers  of  the  corpus  callosum 
a  stimulus  is  conveyed  to  the  right  cortex  when  the  movement 
affects  the  musculature  of  the  left  side. 

The  Corpora  Striata  and  Thalami. — The  numerous  masses 
of  gray  matter  found  in  the  cerebrum  beneath  the  cortex, 
in  the  thalamencephalon,  and  in  the  midbrain  have  each,  of 
course,  specific  functions,  but,  in  general,  it  may  be  said  that 
they  are  intercalated  on  the  afferent  or  efferent  paths  to  or  from 
the  cortex.  Their  physiology  is  included,  therefore,  in  the 
description  of  the  functions  mediated  by  these  paths.  For 
instance,  the  lateral  geniculate  bodies  form  part  of  the  optic 
path.  In  addition,  however,  these  masses  of  cells  contain 
in  many  cases  reflex  arcs  of  a  more  or  less  complicated  kind, 
through  which  afferent  impulses  are  converted  into  efferent 
impulses  that  affect  the  musculature  or  the  glandular  tissues 
of  the  body.  The  large  nuclei  constituting  the  corpora  striata 
(nucleus  caudatus  and  n.  lenticularis)  and  the  thalami  have 
been  frequently  studied  experimentally  to  ascertain  whether 
they  have  specific  functions  independently  of  their  relations  to 
the  cortex.  Older  experiments  (Nothnagel),  in  which  the  attempt 
was  made  to  destroy  these  nuclei  by  the  localized  injection  of 
chromic  acid,  are  probably  unreliable,  as  the  destruction  involved 
also  the  projection  fibers  passing  to  the  cortex.  More  recent  work 
has  seemed  to  indicate  quite  specific  functions  for  these  structures. 
The  optic  thalamus  is  intercalated  on  the  sensory  paths  and  plays 
an  important  part  in  correlating  the  activity  of  the  afferent  system. 
The  corpus  striatum,  on  the  contrary,  has  motor  functions.  The 
nuclei  of  the  corpus  striatum  (the  nucleus  caudatus,  the  globus 
pallidus,  and  the  putamen)  are  not  connected  directly  with  the 
cortex  of  the  cerebrum,  although  there  are  indirect  connections 
through  the  thalamus;  but  they  are  connected  with  the  red  nucleus 
*  Liepmann,  "Med.  Klin.,"  1907,  725. 


232  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

and  thus  brought  into  relation  with  the  motor  system  to  the  cord 
known  as  the  rubrospinal  tract.  Lesions  of  the  nucleus  caudatus 
are  accompanied  by  marked  disturbances  in  heat  regulation,  so 
that  many  authors  assume  the  existence  of  a  heat-regulating  center 
in  this  nucleus.  Others  have  suggested  that  the  corpus  striatum 
constitutes  a  regulating  center  for  the  control  of  the  more  primitive 
or  automatic  movements,  such  as  walking,  posture,  etc.,  and  have 
described  a  motor  or  pallidal  system  arising  chiefly  in  the  large 
cells  of  the  globus  pallidus  through  which  these  motions  are 
mediated.  According  to  Hunt,*  pathological  lesions  (atrophy)  of 
the  cells  of  the  globus  pallidus  are  followed  by  paralysis  agitans, 
while  lesions  of  the  other  nuclei  manifest  themselves  in  choreic 
movements.  With  regard  to  the  various  nuclei  of  the  thalamus,  it 
is  known  that  they  form  abundant  connections  with  the  sensory 
areas  of  the  cortex  cerebri,  and  from  this  standpoint  they  may  be 
regarded  as  consisting  of  subcenters,  with  a  probability,  however, 
that  reflexes  may  occur  through  them  (subcortical  reflexes)  inde- 
pendently of  the  cortex.  Numerous  fibers  have  been  traced  from 
the  thalamus  to  the  body  sense  area  (Flechsig) .  Sachs  f  states  that 
the  thalamus  may  be  considered  as  being  composed  of  two  prac- 
tically independent  parts:  an  inner  division,  which  has  relation 
with  the  nucleus  caudatus  and  the  rhinencephalon,  and  an  outer 
division,  which,  on  the  one  hand,  serves  as  a  terminus  for  the  fibers 
of  the  lemniscus  and  of  the  superior  cerebellar  peduncle,  and,  on  the 
other  hand,  is  connected  by  afferent  and  efferent  paths  with  the 
cortex  of  the  Rolandic  region.  It  is  evident,  from  these  relations 
and  from  the  proximity  of  the  internal  capsule,  that  lesions  in  the 
thalamus  may  occasion  symptoms  of  a  very  diverse  character. 
Among  these  symptoms,  we  should  expect  to  find  hemianesthesia 
on  the  opposite  side,  owing  to  the  fact  that  the  thalamus  serves 
as  a  substation  for  the  fibers  of  the  lemniscus. 

*  Hunt,  "Brain,"  1917,  40,  58. 
t  Sachs,  "Brain,"  1909,  1. 


CHAPTER  XI. 

THE  FUNCTIONS  OF  THE  CEREBELLUM,  THE  PONS, 
AND  THE  MEDULLA. 

P 

The  functions  of  the  cerebellum  are,  in  some  respects,  less  satis- 
factorily known  than  those  of  any  other  part  of  the  central  nervous 
system.  Many  theories  have  been  held.  Most  of  these  views 
have  been  attempts  to  assign  to  the  organ  a  single  function  of  a 
definite  character,  but  latterly  the  insufficiency  of  the  theories 
proposed  has  led  observers  to  attribute  to  the  cerebellum  general 
properties  the  nature  of  which  can  not  be  expressed  satisfactorily 
in  a  single  phrase.  Before  attempting  to  give  a  summary  of  exist- 
ing views  it  will  be  helpful  to  recall  briefly  the  important  facts  re- 
garding its  structure  and  relations,  so  far  as  they  are  known  and  can 
be  used  to  explain  its  functional  value. 

Anatomical  Structure  and  Relations  of  the  Cerebellum.— 
The  finer  histology  of  the  cerebellar  cortex  is  represented  in  Fig. 
103.  Three  layers  may  be  distinguished.  The  external  molecular 
layer  (A),  the  middle  granular  layer  (B),  and  the  internal  medullary 
layer  consisting  of  the  white  matter  or  medullated  nerve  fibers, 
afferent  and  efferent  (C).  Between  the  molecular  and  granular 
layers  lie  the  large  and  characteristic  Purkinje  cells  (a).  The 
dendrites  of  these  cells  branch  profusely  in  the  molecular  layer; 
then*  axons  pass  into  the  medullary  layer.  From  the  standpoint 
of  the  neuron  doctrine  these  cells,  so  far  as  the  cerebellum  is  con- 
cerned, are  efferent.  They  form,  indeed,  the  sole  efferent  system 
of  the  cerebellar  cortex.  The  afferent  fibers  of  the  cerebellum  end 
in  both  the  granular  and  the  molecular  layers.  Those  that  termi- 
nate in  the  granular  layer— designated  by  Cajal  as  moss  fibers, 
have  at  their  terminations  and  points  of  branching  curious  clumps 
of  small  processes;  they  probably  connect  with  the  dendrites  of  the 
nerve  cells  in  this  layer.  Those  that  pass  deeper  into  the  molec- 
ular layer  come  into  connection  with  the  dendrites  of  the  Purkinje 
cells,  around  which,  indeed,  they  seem  to  twine,  so  that  Cajal  desig- 
nated them  as  climbing  fibers.  The  granular  layer  (B)  contains 
numerous  granules  (g)  or  small  nerve  cells.  These  cells  are  spherical, 
and  have  a  relatively  large  nucleus  and  a  small  amount  of  cyto- 
plasm. Their  dendrites  are  few  and  short;  their  axons  run  into 
the  molecular  layer,  divide  in  T,  and  the  two  branches  then  run 
parallel  to  the  surface  and  doubtless  make  connections  with  the  den- 

233 


234  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

drites  of  the  Purkinje  cells  as  well  as  with  the  cells  of  the  molecular 
layer.  A  few  larger  nerve  cells  of  Golgi's  second  type  (/)  are  found 
also  in  the  granular  layer.  In  the  molecular  layer  are  found  two 
types  of  cells :  the  larger  basket  cells  (&)  whose  axons  terminate  in  a 
group  of  small  branches  that  inclose  the  body  of  the  Purkinje  cells, 
and  a  number  of  smaller  cells  (e),  situated  more  superficially, 
whose  axons  pass  longitudinally  in  the  molecular  layer  and  termi- 
nate in  arborizations  or  baskets  that  doubtless  make  connections 
with  the  dendrites  of  the  Purkinje  cells. 


\(C 
Fig.  103.— Histology  of  the  cerebellum.— (From  Oberateiner.) 

A  consideration  of  this  peculiar  and  intricate  structure  enables 
us  to  comprehend  that  the  cerebellar  cortex  presents  a  reflex  arc 
of  a  very  considerable  degree  of  complexity.  The  incoming  im- 
pulses through  the  moss  and  climbing  fibers  may  pass  at  once  to  the 
Purkinje  cells  and  lead  to  efferent  discharges,  or  they  may  end  in 
the  cells  of  the  granular  or  molecular  layer  and  thus  be  distributed 
to  the  Purkinje  cells  in  a  more  indirect  way.  In  addition  to  the 
cortex  the  cerebellum  contains  several  masses  of  gray  matter  in 
its  interior:  the  large  dentate  nucleus  in  the  center  of  each  hemi- 
sphere and  the  group  of  nuclei  lying  in  or  near  the  middle  of  the 
medullary  substance  of  the  vermiform  lobe  (nucleus  fastigii,  n. 


CEREBELLUM,    PONS,    AND    MEDULLA.  235 

globosi,  and  the  n.  embolif ormis) .  The  axons  of  the  Purkinje 
cells  of  the  cortex  terminate  in  these  subcortical  nuclei,  and  the 
efferent  path  from  the  cerebellum  is  then  continued  by  new 
neurons.  Thus,  the  fibers  of  the  superior  peduncles  (brachium 
conjunctivum)  of  the  cerebellum  arise  chiefly  from  the  dentate 
nuclei,  and  only  indirectly  from  the  cortex.  The  anatomical 
connections,  afferent  and  efferent,  between  the  cerebellum  and 
other  parts  of  the  nervous  system  are  very  complex  and  not 
yet  entirely  known.  Without  attempting  to  recall  all  of  these 
connections,  which  will  be  found  described  in  works  upon  anat- 
omy or  neurology,  emphasis  may  be  laid  upon  those  which  are 
at  present  helpful  in  discussing  the  physiology  of  the  organ. 

1.  Connections  with  the  Afferent  Paths  of  the  Cord. — Through  the 
inferior  peduncles  (restiform  bodies)  the  cerebellum  receives  affer- 
ent fibers  from  the  spinal  cord  and  the  medulla.  The  cerebello- 
spinal  fasciculus  undoubtedly  terminates  in  the  cerebellum,  and 
according  to  some  observers  the  fibers  of  the  posterior  funiculi 
after  ending  in  the  n.  gracilis  and  n.  cuneatus  are  also  continued 
in  part  to  the  cerebellum  by  nerve  fibers  passing  by  way  of  the 
inferior  peduncles.  This  latter  view  has,  however,  not  found 
confirmation  in  recent  work,  most  authors  believing  that  the 
afferent  fibers  of  the  posterior  funiculi  all  enter  the  lemniscus, 
after  decussating,  and  pass  forward  to  the  thalamus.  Ascending 
fibers  arising  in  the  reticular  formation  of  the  medulla  and  the 
olivary  nucleus  may  take  this  path  to  the  cerebellum,  and,  on  the 
other  hand,  may  make  connections  with  the  sensory  tracts  of 
the  cord  or  the  sensory  nuclei  of  the  medulla.  Another  afferent 
tract  of  the  cord,  that  of  Gowers  (fasciculus  anterolateralis  super- 
ficialis),  ends  in  the  cerebellum,  in  large  part  at  least,  forming  a 
part,  in  fact,  of  the  cerebellospinal  system.  The  nature  of  the 
sensory  impulses  conveyed  in  this  way  to  the  cerebellum  is  not 
entirely  understood,  but  it  seems  certain  that  some  of  them,  at 
least,  arise  in  the  deeper  tissues,  the  muscles  and  joints.  This 
tract  and  the  similar  tract  of  Flechsig,  by  forming  an  afferent  con- 
nection between  the  deep  tissues  and  the  cerebellum,  present  a 
mechanism  which  may  be  used  to  explain  the  influence  exercised 
by  the  cerebellum  upon  muscular  activity. 

2.  Connections  with  the  Vestibular  Branch  of  the  Eighth  Cran- 
ial Nerve. — This  branch,  arising  in  the  semicircular  canals  and 
utriculus  and  sacculus,  ends  in  the  pons  in  several  nuclei  (Deiters', 
Bechterew's)  and  also  in  the  n.  fastigii  of  the  cerebellum.  These 
nuclei,  in  turn,  are  connected  with  other  parts  of  the  central 
nervous  system,  but  the  details  are  not  yet  completely  known. 
The  connections  that  have  been  most  clearly  established  are 
those  made  with  the  motor  centers.  Through^  the  medial  longi- 


236 


PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 


tudinal  fasciculus  these  nuclei  are  connected  with  the  motor 
nuclei  of  the  cranial  nerves  and  with  descending  paths  in  the  spinal 
cord  (vestibulospinal),  which  end  in  the  motor  centers  for  the  spinal 
nerves.  In  how  far  the  vestibular  nuclei  may  make  afferent  con- 
nections with  the  cerebellum  is  undecided,  but  it  seems  probable 


Fig.  104. — Diagram  to  indicate  a  possible  descending  path  from  cerebrum  to  cord  in  ad- 
dition to  the  pyramidal  system,  namely,  the  secondary  or  cerebellar  motor  path  (Van 
Gehuchten).  The  path  is  indirect  and  comprises  the  following  units:  1.  The  cortico- 
ponto-cerebellar  path,  represented  as  arising  in  tne  motor  area  of  the  cerebrum  and  passing 
down  with  the  pyramidal  system  to  end  in  the  pons,  thence  continued  through  the  middle 
peduncles  to  the  cerebellar  cortex  of  opposite  side.  2.  The  path  from  the  cerebellar  cortex 
to  the  dentate  nucleus.  3.  The  path  from  the  dentate  nucleus  to  the  red  nucleus  passing 
by  way  of  the  superior  peduncles,  brachium  conjunctivum.  4.  The  path  from  the  red 
nucleus  to  the  motor  cells  of  the  spinal  cord  (rubro-spinal  tract). 

that  such  tracts  exist,  in  view  of  the  fact  that  destruction  of  the 
semicircular  canals  and  severe  lesions  of  the  cerebellum  cause  motor 
disturbances  that  are  strikingly  similar. 

3.  Connections  with  Other  Sensory  Nuclei. — In  addition  to  the 
special  sensory  connections  just  described,  it  is  stated  by  various 
neurologists  that  the  sensory  nuclei  of  the  vagus,  the  trigeminal 
and  the  auditory  nerves,  send  afferent  paths  into  the  cerebellum, 


CEREBELLUM,    PONS,    AND    MEDULLA.  237 

and  that  similar  paths  extend  from  the  primary  end  stations  of 
the  optic  fibers.* 

4.  Connections  with  the  Cortex  of  the  Cerebrum. — The  cerebellar 
cortex  is  connected  with  the  cerebral  cortex  by  the  large  system 
known  as  the  cortico-ponto-cerebellar  tract  (see  Fig.  82,  A).  The 
fibers  of  this  tract  arise  in  the  motor  area  of  the  cerebrum  or  in  the 
frontal  cortex  anterior  to  the  motor  area,  descend  in  the  internal 
capsule  and  cerebral  peduncle,  and  end  in  the  gray  matter  of 
the  pons.  Thence  new  axons  continue  the  path  across  the 
mid-line  and  to  the  cerebellar  cortex  by  way  of  the  middle 
peduncle  (brachium  pontis).  The  tract  would  seem  to  convey 
efferent  impulses  from  the,  cerebral  cortex  (motor  region)  of 
one  side  to  the  cerebellar  cortex  of  the  opposite  side.  A  second 
possible  connection  with  the  cerebrum  is  made  by  way  of  the 
thalamus.  Fibers  arising  in  the  dentate  nucleus  emerge  by 
way  of  the  brachium  conjunctivum  and  connect  with  the  red 
nucleus  in  the  subthalamic  region  and  perhaps  also  with  the 
thalamus.  The  latter  fibers  may  be  continued  forward  to  the 
cortex  of  the  cerebrum  and  thus  constitute  an  afferent  path  from 
cerebellum  to  cerebrum.  Those  fibers,  on  the  contrary,  which  end 
in  the  red  nucleus  are  brought  into  reflex  connection  with  the 
motor  bundle  (rubrospinal  tract),  extending  from  the  red  nucleus 
to  the  motor  centers  in  the  spinal  cord.  Making  use  of  the  connec- 
tions described  above,  Van  Gehuchten  pictures  an  indirect  motor 
path  from  the  cortex  of  the  cerebrum  to  the  motor  nerves  by  way 
of  the  cerebellum  (see  Fig.  104).  The  motor  impulses  descend  by 
way  of  the  cortico-ponto-cerebellar  path  to  the  cerebellar  cortex, 
thence  to  the  dentate  nucleus,  thence  to  the  red  nucleus,  and  then, 
by  way  of  the  rubrospinal  tract,  to  the  motor  nuclei  of  the  spinal 
nerves. 

Theories  Concerning  the  Functions  of  the  Cerebellum.— 
Modern  views  concerning  the  functions  of  the  cerebellum  may  be 
classified  under  three  general  heads:  First,  those  that  consider  it 
a  general  co-ordinating  center  or  organ  for  the  muscular  movements 
and  especially  for  those  concerned  in  equilibrium  and  locomotion. 
This  view,  first  proposed  essentially  by  Flourens  (1824),  has  been 
adopted  by  many,  perhaps  by  most,  writers  since  his  time.  The 
manner  in  which  the  organ  serves  to  co-ordinate  these  movements 
has  been  explained  in  various  ways.  According  to  the  older  ob- 
servers, it  was  supposed  so  to  arrange  or  group  the  various  motor 
impulses  that  they  reached  the  lower  motor  centers  in  the  cord 
in  the  necessary  combination  for  co-ordinated  contractions.  Ac- 
cording to  more  recent  observers,  this  synergetic  action  is  exer- 
cised not  directly  on  the  motor  side  of  the  reflex  but  on  the  sensory 
*  See  Edinger,  "  Brain,"  29,  483,  1906. 


238  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

side.  The  numerous  sensory  paths  connected  with  the  organ,  es- 
pecially those  of  the  muscular  sense,  and  those  from  the  vestibular 
nerve,  suggest  the  view  that  in  the  complex  cortex  of  the  cerebel- 
lum these  afferent  impulses  act  upon  nervous  combinations  whose 
discharges  in  turn  are  conveyed  to  the  motor  centers  in  a  definite 
and  orderly  sequence.  Either  point  of  view  assumes  that  there 
are  in  the  cerebellum  certain  distinct  mechanisms — that  is,  combi- 
nations of  neurons  that  are  essentially  reflex  centers,  and  that  in 
all  of  our  more  complex  bodily  movements  these  mechanisms 
intervene.  The  second  general  set  of  theories  regarding  the  cere- 
bellum assumes  that  this  organ  is  essentially  the  center  or  a  center 
for  the  muscle  sense.  This  view  is  connected  usually  with  the  name 
of  Lussana,*  but  has  been  supported  since  in  one  sense  or  another 
by  many  observers,  f  It  is,  in  fact,  not  essentially  different  per- 
haps from  the  second  phase  of  the  first  group  of  theories.  Those 
who  have  expressed  their  idea  of  the  physiology  of  the  cerebellum 
by  saying  that  it  is  a  center  of  the  muscle  sense  have,  in  recent 
times  at  least,  recognized  that  this  sense  has  a  cortical  center  also  in 
the  cerebrum.  The  view  can  not  assume,  therefore,  a  conscious 
muscle  sense  mediated  by  the  cerebellum,  but  only  that  fibers  of 
deep  sensibility  have  a  cortical  termination  therein,  and  that 
the  cerebellar  activity  thus  aroused  is  in  some  way  necessary  to 
the  orderly  adjustment  of  complex  voluntary  movements.  Some 
authors  have  assumed  that  the  reflex  effect  thus  exerted  on  the  mus- 
culature of  the  limbs  and  trunk  is  not  concerned  directly  in  elaborat- 
ing the  proper  co-ordination  of  the  muscles,  but  consists  essentially 
in  the  production  of  a  state  of  tonus  of  a  variable  or  adaptive  char- 
acter, which  serves  as  a  foundation,  so  to  speak,  for  the  volun- 
tary control  of  the  muscles.  It  would  seem  to  be  evident  that  on 
any  theory  of  this  kind  the  results  of  cerebellar  activity  must  be 
exerted  through  some  efferent  channel  upon  the  muscles  concerned 
in  equilibrium  and  body-movements.  No  direct  efferent  path  be- 
tween the  cerebellar  cortex  and  the  motor  centers  of  the  cord  has 
been  established  satisfactorily,  but  it  may  be  that  the  indirect  path 
through  the  superior  peduncles  to  the  red  nucleus  and  thence  to  the 
cord  through  the  rubrospinal  tract  subserves  this  function.  Accord- 
ing to  another  point  of  view,  the  cerebellum  is  a  great  augmenting 
organ  for  the  neuromuscular  system.  It  is  added  on,  as  it  were,  to 
the  cerebrospinal  motor  system,  and  serves  not  to  co-ordinate  the 
motor  discharges,  but  to  increase  their  strength  or  effectiveness. 
This  general  view,  first  proposed  by  Weir  Mitchell  (1869),  has  been 
supported  by  Luys,  and  especially,  although  with  important 

*  Lussana.     See  "Journal  de  la  physiol.  de  1'homme,"  5,  418,  1862. 
t  See  Lewandowsky,  "Archiv  f.  Physiologie,"  1903,  129. 


CEREBELLUM,    PONS,    AND    MEDULLA.  239 

modifications,  by  Luciani.*     Some  of  the  details  of  the  work  of 
the  latter  observer  are  given  below. 

Experimental  Work  Upon  the  Cerebellum. — Rolando,  and  par- 
ticularly Flourens,  gave  the  direction  to  modern  experimentation 
in  this  subject.  The  latter  observer  made  numerous  observations, 
especially  on  pigeons,  in  regard  to  the  effect  of  removing  all  or  a 
part  of  the  cerebellum.  He  describes  in  detail  the  striking  results 
of  such  an  operation.  When  all  or  a  large  part  of  the  organ  is  re- 
moved the  animal  shows  a  most  distressing  inability  to  stand  or 
move.  There  seems  to  be  no  muscular  paralysis,  but,  at  first, 
a  total  lack  of  power  to  co-ordinate  properly  the  contractions  of  the 
various  muscles  involved  in  maintaining  equilibrium.  The  animal 
takes  a  most  abnormal  position,  with  the  head  retracted  and 
twisted,  and  any  attempt  to  move  is  followed  by  violent  disorderly 
contractions  that  may  result  in  a  series  of  involuntary  somersaults. 
The  animal  is  totally  unable  to  fly.  When  the  injury  to  the  cere- 
bellum is  less  the  effect  upon  the  movements  is  either  too  slight 
to  be  noticed  or  is  shown  hi  a  greater  or  less  uncertainty  hi  its 
movements.  When  it  attempts  to  walk,  for  instance,  it  exhibits 
a  staggering,  drunken  gait,  a  condition  designated  as  cerebellar 
ataxia.  Similar  operations  on  mammals  give  in  general  the  same 
results.  If  the  operation  is  unilateral, — that  is,  affects  only  one 
hemisphere, — the  animal  (dog)  exhibits  forced  movements,  such 
as  a  tendency  to  roll  around  the  long  axis  of  his  body  toward  the 
injured  side  and  subsequently  movements  in  a  circle  toward  the  same 
side.  In  man  there  are  several  cases  on  record  in  which  the 
organ  was  shown  by  autopsy  to  be  largely  or  completely  atro- 
phied, and  numerous  cases  of  tumors  affecting  the  cerebellum 
have  also  been  reported.  In  the  latter  group  of  cases  there 
may  be  certain  marked  subjective  symptoms,  such  as  headache, 
and  especially  vertigo,  but  on  the  objective  side  the  neurologists 
emphasize  the  fact  that  in  cerebellar  disorders  the  lack  of  accurate 
co-ordination  or  asynergy  is  the  fundamental  symptom.  This 
condition  may  be  manifested  by  an  ataxic  gait,  by  muscular 
tremors,  and,  especially,  by  lack  of  skill  in  performing  certain 
definite  movements  which  require  the  associated  activity  of  several 
muscles — for  example,  the  placing  of  the  finger  to  the  nose  or 
the  rapid  alternation  in  the  contraction  of  antagonistic  muscles, 
abduction  and  adduction,  or  pronation  and  supination.f  So 

*  For  the  literature  of  the  cerebellum,  see  Luciani,  "II  cervelleto,"  Flor- 
ence, 1891;  German  translation,  "Das  Kleinhirn,"  1893.  Also  Luciani,  article 
"Das  Kleinhirn/'  in  "Ergebnesse  der  Physiologic,"  vol.  iii,  part  ii,  p.  259, 
1904,  and  van  Rynberk,  ibid.,  653,  1908. 

f  Mills  and  Weisenburg,  "Journal  of  the  American  Medical  Association," 
November  21,  1914. 


240  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

also  in  the  cases  of  atrophy,  in  which  probably  the  condition  devel- 
ops slowly  through  a  number  of  years,  a  degree  of  ataxia  is  ex- 
hibited, especially  when  the  movements  are  rapid  and  forced. 
In  the  ataxic  condition  resulting  from  tabetic  lesions  of  the 
posterior  funiculi  the  effect  upon  the  movements  is  increased 
by  covering  up  the  eyes  (Romberg's  symptom),  the  individual 
being  then  deprived  of  his  visual  stimuli  as  well  as  those  coming 
by  way  of  the  muscular  and  cutaneous  nerves.  In  cerebellar 
ataxia,  however,  the  effect  is  not  increased  by  closure  of  the 
eyes,  a  result  which  is  probably  explained  by  the  fact  that  the 
individual  still  possesses  his  paths  of  muscular  and  cutaneous 
sensibility  to  the  cerebrum,  and  these  senses  may  be  used  in  the 
reflex  adjustments  of  voluntary  movements. 

Interpretation  of  the  Experimental  and  Clinical  Results.— 
Flourens  was  led  by  the  striking  results  of  his  operations  on  pigeons 
to  suggest  the  view  that  the  cerebellum  is  an  organ  for  the  co- 
ordination of  the  movements  of  equilibrium  and  locomotion. 
Objections  were  raised  to  this  view.  Some  observers  (Dal ton, 
Weir  Mitchell)  found  that  if  the  pigeons  from  which  the  cerebellum 
had  been  removed  were  kept  long  enough  the  effects  first  observed 
gradually  disappeared,  so  that  finally  the  animals  were  able  to 
move  or  fly  with  no  marked  difference  from  the  normal  animal 
except  that  fatigue  was  shown  much  more  quickly.  Hence  the 
view  advocated  by  Mitchell  that  the  essential  function  of  the 
cerebellum  is  that  of  an  augmenting  apparatus  for  the  voluntary 
movements.  With  regard  to  this  view  it  may  be  remarked  in 
passing  that  pigeons  with  the  cerebral  hemispheres  removed  exhibit 
apparently  as  a  permanent  symptom  the  same  tendency  to  rapid 
fatigue  after  sustained  muscular  effort.  By  the  same  logical  process 
therefore  one  might  conclude  that  one  function  of  the  cerebrum 
is  that  of  an  augmenting  organ  to  the  motor  discharges  from  the 
cerebellum  or  midbrain.  So  also  the  cases  of  complete  or  nearly 
complete  atrophy  of  the  cerebellum  in  human  beings  in  which  no 
evil  result  follows  other  than  a  slight  degree  of  cerebellar  ataxia 
have  been  used  as  an  argument  against  the  view  that  this  organ 
is  necessary  to  the  co-ordination  of  the  complex  voluntary  move- 
ments. The  view  that  the  cerebellum  has  essentially  a  direct 
co-ordinating  function  has  been  criticized  most  seriously  by  Luciani. 
This  observer  made  a  series  of  long-continued  and  most  careful 
observations  upon  dogs  and  monkeys  in  which  the  entire  cere- 
bellum or  certain  definite  parts  had  been  removed.  He  lays  stress 
upon  the  fact  that  the  violent  disturbance  of  movement  is  tem- 
porary and  is  slowly  recovered  from  in  time.  He  was  led,  therefore, 
to  view  these  disturbances  as  due  primarily  not  to  the  loss  of  the  nor- 


CEREBELLUM,    PONS,    AND    MEDULLA.  241 

mal  functional  activity  of  the  organ,  but  to  irritations  resulting  from 
the  operation.  When  this  stage  of  irritation  is  passed  the  real 
defects  which  indicate  the  true  function  of  the  cerebellum  become 
apparent.  These  defects  exhibit  themselves  as  a  loss  of  power 
in  the  neuromuscular  apparatus  of  the  complex  voluntary  move- 
ments, and  he  analyzes  these  results  under  three  heads:  First, 
a  loss  of  force  in  the  muscular  contractions, — a  condition  of  asthenia ; 
second,  a  loss  of  tone  in  the  muscles  of  the  limbs  and  trunk,  par- 
ticularly in  the  hind  limbs, — a  condition  of  atonia;  and,  third,  a 
loss  of  steadiness  in  the  muscular  contractions, — a  condition  of 
astasia.  The  astasia  manifests  itself  in  a  tremor  of  the  muscles 
when  voluntarily  contracted,  especially  in  movements  requiring 
much  exertion.  Luciani  supposes  that  this  tremor  is  due  to  an 
alteration — that  is,  a  slowing — of  the  rhythm  of  discharges  of  the 
impulses  from  the  motor  centers.  The  functions  of  the  cerebellum 
on  his  theory  are  expressed,  therefore,  by  saying  that  it  is  an  aug- 
menting organ  for  the  activity  of  the  neuromuscular  apparatus ;  and 
that,  so  far  as  this  augmenting  or  strengthening  activity  can  be  ana- 
lyzed, it  consists  in  an  increase  in  the  energy  of  the  motor  discharges 
(sthenic  action),  an  increase  in  the  tension  or  tone  of  the  motor 
centers  and  their  connected  muscles  (tonic  action) ,  and  an  increase 
in  the  rhythm  of  the  motor  impulses  (static  action)  so  that  nor- 
mally the  muscular  contractions  are  of  the  nature  of  complete 
tetani.  Luciani  believes  that  this  action  of  the  cerebellum  is 
continuous,  although  varying  in  intensity,  and  that  it  affects  all 
of  the  musculature  of  the  body,  and  not  simply  the  muscles  con- 
cerned in  body  equilibrium.  This  constant  motor  activity  is  in 
turn  dependent  upon  a  constant  inflow  of  sensory  impulses  into 
the  cerebellum  along  its  afferent  connections,  particularly  upon  the 
impulses  from  the  vestibular  portion  of  the  internal  ear,  and  those 
from  the  muscle  sense  fibers  and  similar  fibers  of  so-called  deep 
sensibility.  The  constant  augmenting  activity  of  the  cerebellum 
is,  therefore,  a  species  of  reflex  effect, — a  reflex  tonus  which 
affects  all  the  musculature.  Whether  the  cerebellar  mechanism 
is  especially  arranged  to  co-ordinate  its  effect  upon  the  neuro- 
muscular apparatus — that  is,  in  some  way  to  adapt  the  move- 
ments to  a  definite  end — Luciani  leaves  an  open  question.  He 
does  not  believe  that  a  lack  of  co-ordination  (cerebellar  ataxia) 
is  necessarily  present  in  cerebellar  lesions;  but  admits  that,  if  this 
symptom  is  an  invariable  one,  it  would  be  necessary  to  add  to 
the  general  augmenting  activity  of  the  cerebellum  also  a  general 
adaptive  or  co-ordinating  activity.  It  is  precisely  this  latter  feature 
which  stands  out  in  the  minds  of  most  physiologists  as  the 
characteristic  function  of  the  cerebellum,  while  Luciani  considers 
that  it  is  not  demonstrated  by  clinical  or  experimental  facts,  and 
16 


242  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

that  even  if  demonstrated  it  would  have  to  be  considered  as  a 
part — perhaps  a  subordinate  part — of  the  functional  influence  of 
this  organ. 

Conclusions  as  to  the  General  Functions  of  the  Cerebel- 
lum.— It  is  evident  that  an  authoritative  statement  of  the  function 
or  functions  of  the  cerebellum  is  impossible.  It  seems  quite  clear, 
however,  that  the  organ  exerts  a  regulating  influence  of  some  kind 
upon  the  neuromuscular  apparatus  of  our  so-called  voluntary 
movements.  The  precise  nature  of  the  regulating  influence  is  in 
dispute,  and  one  who  reads  the  literature  finds  it  difficult  at  times 
to  separate  clearly  the  different  theories  proposed,  since  some 
authors  are  content  with  general  statements  and  others  attempt 
a  more  specific  analysis.  On  the  whole,  it  seems  desirable  at 
present  to  hold  to  the  general  idea,  introduced  by  Flourens,  that 
the  cerebellum  te  a  central  organ  for  co-ordination  of  voluntary 
movements,  particularly  the  more  complex  movements  necessary 
in  equilibrium  and  locomotion.  Instead,  however,  of  assuming 
with  Flourens  that  the  cerebellum  contains  a  co-ordinating  principle, 
an  expression  that  means  nothing  at  present,  we  may  assume  that 
it  exerts  its  co-ordinating  influence  by  virtue  of  the  definite  nervous 
mechanisms  contained  in  it — that  is,  by  nervous  complexes  which, 
on  the  afferent  side,  are  connected  with  the  peripheral  sensory 
nerves  to  the  vestibule  of  the  ear,  the  muscles,  joints,  etc.,  and  on 
the  efferent  side  are  in  direct  or  indirect  relations  with  the  motor 
centers  of  the  cord.  Co-ordinated  movements  requiring  the  com- 
bined and  sustained  activity  of  a  number  of  muscles  depend  in 
some  way  upon  a  combination  of  the  activity  of  these  mechanisms 
with  the  discharging  mechanisms  farther  forward  in  the  brain 
(cerebrum).  Whether  this  co-activity  consists  in  the  addition  of 
a  tonic  element  to  the  impulses  proceeding  from  the  cerebrum,  as 
would  be  implied  by  the  results  of  Luciani's  experiments,  or  whether 
the  cerebellum  participates,  through  some  form  of  representation 
of  these  movements,*  based  upon  the  afferent  impulses  received 
through  the  paths  already  described,  cannot  be  settled  at  present. 
Luciani's  conception  has  the  recommendation  of  being  based  upon 
a  large  amount  of  experimental  work,  and  it  may  be  included  or 
utilized  in  a  general  theory  of  a  co-ordinating  function  of  the  cere- 
bellum, if  we  assume  that  the  effect  of  this  organ  on  muscular  ton- 
icity  is  adaptive,  that  is  to  say,  varies  in  a  definite  way  in  the 
different  muscles  according  to  the  character  of  the  afferent  im- 
pulses received  from  the  muscles,  joints,  labyrinth,  etc.  That  an 
adaptive  tonicity  of  the  muscles  actually  occurs  is  demonstrated 
by  experiments  (see  p.  411),  and  we  can  understand  that  a  regu- 
lated tonicity  of  this  kind  may  constitute  the  foundation  upon 
*  See  Horsley,  "Brain,"  1906,  446. 


CEREBELLUM,    PONS,    AND    MEDULLA.  243 

which  the  normal  co-ordination  of  the  muscles  is  effected.  The 
fact  that  in  birds  as  well  as  in  higher  forms  the  animal  eventually 
learns  to  co-ordinate  such  movements  after  the  loss  of  the  cerebel- 
lum does  not  invalidate  this  conclusion.  In  the  first  place,  the 
recovery  in  such  cases  is  not  entirely  complete,  since  some  ataxia 
is  still  manifested  in  vigorous  or  hurried  movements,  and  the 
amount  of  restoration  of  normal  activity  which  is  obtained  may 
be  referred  to  a  possible  adaptation  or  training  in  the  cerebral 
portion  of  the  mechanism.  The  relative  parts  taken  by  the 
cerebellum  and  the  cerebrum  in  such  movements  vary  probably  in 
different  animals  and  in  different  movements  in  the  same  animal. 
Removal  of  the  cerebrum  from  a  pigeon  leaves  an  animal  with 
almost  perfect  power  of  controlling  its  equilibrium.  In  the  dog  a 
similar  operation  is  followed  by  a  longer  period  of  inability  to  con- 
trol perfectly  the  movements  of  locomotion,  and  it  is  probable 
that  in  man  after  such  an  operation  the  power  of  locomotion  would 
be  acquired  more  slowly,  if  at  all.  On  the  other  hand,  the  violent 
effect  upon  such  movements  caused  by  the  removal  of  the  cerebel- 
lum in  the  pigeon  is  less  evident  in  the  dog,  and,  if  we  may  judge 
from  the  incomplete  data  of  clinical  neurology,  very  much  less 
evident  in  man.  In  man  the  motor  control  of  the  voluntary 
muscular  system  through  the  cerebrum  is  more  highly  developed 
than  in  the  lower  animals. 

The  Psychical  Functions  of  the  Cerebellum. — In  the  cerebel- 
lum, as  in  the  other  nerve  centers  below  the  cerebrum,  we  have  to 
consider  the  possibility  of  a  psychical  or  conscious  side  to  the  activity 
of  the  organ.  It  seems  clear,  however,  that  the  degree  of  conscious- 
ness, if  any,  exhibited  by  the  cerebellum  is  of  a  much  lower  order 
than  that  shown  by  the  cerebrum.  All  observers  agree  that  there 
is  no  apparent  loss  of  sensations  after  removal  of  the  cerebellum, 
but  Luciani,  Russell,  and  others  state  their  belief  that  in  some 
indefinable  way  the  mentality  of  the  animal  is  affected  by  such 
operations.  Whatever  functions  of  this  kind  are  present  we  can 
define  only  by  the  unsatisfactory  term  of  subconscious  rather  than 
unconscious.  As  far  as  can  be  determined,  this  effect  is  felt  mainly 
upon  the  muscular  sense  and  the  sense  of  position  and  of  direction. 

Localization  of  Function  in  the  Cerebellum. — All  observers 
agree  that  so  far  as  the  influence  of  the  cerebellum  on  the  muscula- 
ture of  the  body  is  concerned,  it  is  homolateral, — that  is,  each 
half  of  the  cerebellum  is  connected  with  its  own  half  of  the 
body.  The  connection  with  the  motor  areas  of  the  brain  is  the 
reverse,  the  right  half  of  the  cerebrum  being  in  relation  with  the 
left  half  of  the  cerebellum.  These  relations  are,  in  the  main, 
borne  out  by  the  anatomical  course  of  the  motor  and  sensory 
paths  described  above.  There  arises,  however,  the  question 


244  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

whether  or  not  there  is  a  localization  of  function  in  the  cere- 
bellum, that  is,  whether  definite  parts  of  the  cerebellar  cortex 
are  in  specific  relations  with  separate  muscles  or  groups  of 
muscles.  The  possibility  of  a  localization  of  function  was 
suggested  years  ago  by  experiments  made  by  Ferrier,  in  which 
electrical  stimulation  of  the  cortex  gave  definite  movements 
of  the  head,  limbs,  and  especially  of  the  eyes,  the  movements 
varying  somewhat  according  to  the  part  stimulated.  These 
results  were  not  wholly  confirmed  by  later  observers.  Horsley 
and  Clarke*  state  that  such  strong  stimuli  are  required  to  obtain 
a  decisive  effect  from  the  cortex  of  the  cerebellum  that  it  may  be 
questioned  whether  in  positive  cases  the  result  is  due  to  excita- 
tion of  the  cortex  itself  or  to  an  escape  of  stimulus  to  the  under- 
lying nuclei.  Direct  stimulation  of  the  dentate  nucleus  gave 
them  conjugate  movements  of  the  two  eyes.  These  indications 


Fig.  105. — Schema  of  dog's  cerebellum  to  show  Bolk's  nomenclature  for  the  lobes  and 
sulci.  Dorsal  view  :  La,  lobus  anterior  (this  lobe  is  separated  from  thejarger  posterior  lobe 
by  the  deep  primary  fissure,  Spr) ;  Ls,  lobulus  simplex  ;  Lans,  lobulus  ansiformis ;  Lp, 
lobulus  paramedianus  ;  Lmp,  lobulus  medianus  posterior ;  Fv,  formatis  vermicularis  (pars 
tonsillaris)  ;  C1,  crus  primum ;  C2,  crus  secundum  ;  Spr,  sulcus  primarius  ;  Sp,  sulcus 
paramedianus  ;  Si,  sulcus  intercruralis. — (After  van  Rynberk.) 

of  a  localization  have  been  strengthened  by  the  results  of  com- 
parative anatomy,  and  especially  by  the  effects  of  ablation  of 
definite  parts  of  the  cortex.  Earlier  experimenters,  using  the 
method  of  ablation,  obtained  quite  negative  results  from  the 
standpoint  of  localization,  but  this  seems  to  have  been  due  to 
the  fact  that  a  faulty  anatomical  schema  was  used ;  a  whole  hemi- 
sphere, or  the  entire  vermiform  lobe,  etc.,  was  removed.  Later 
experimenters  f  have  adopted  the  newer  anatomical  schemata, 
which  take  account  of  the  true  genetic  relations  of  the  various 

*  Horsley  and  Clark,  "Brain,"  28,  13,  1905. 

fVan  Rynberk,  "General  Review  in  Ergebnisse  der  Physiologic,"  7, 
653,  1908,  and  12,  533,  1912.  Also  Thomas  and  Durupt,  "Localisations 
cerSbelleuses,"  1914. 


CEREBELLUM,    PONS,    AND    MEDULLA.  245 

lobes  and  lobules  of  the  cerebellum,  and  they  have  been  rewarded 
by  obtaining  results  of  a  positive  character.  The  newer  anatomical 
nomenclature  is  illustrated  in  Fig.  105,  which  gives  a  schematic 
representation  of  the  arrangement  of  the  lobules  of  the  cere- 
bellum of  the  dog,  according  to  Bolk.  Following  this  schema 
van  Rynberk  reports  that  excision  of  the  lobulus  simplex  is 
followed  by  movements  of  the  head  (head  nystagmus),  which 
indicate  an  abnormal  innervation  of  the  neck  muscles.  Injury 
on  one  side  of  the  crus  primum  of  the  ansiform  lobule  is  followed 
by  abnormal  movements  of  the  forefoot  of  the  same  side,  while 
similar  injuries  to  the  crus  secundum  result  in  abnormal  move- 
ments localized  to  the  hind  foot.  Extirpation  of  a  lobulus 
paramedianus  causes  rolling  movements  round  the  long  axis 
of  the  body  or  bending  of  the  body  to  one  side  (pleurothotonus). 
These  experimental  results  have  been  confirmed  in  part  by  obser- 
vations on  clinical  cases  in  which  an  asynergy  of  a  definite  character 
in  the  movements  of  the  arms  or  legs  has  been  related  to  lesions  of 
definite  portions  of  the  cerebellar  hemisphere  of  the  same  side.* 
The  Medulla  Oblongata. — In  the  medulla  oblongata  we  must 
recognize  a  region  of  special  physiological  importance  in  that  it 
is  the  seat  of  certain  centers  which  control  the  activity  of  the 
circulatory  and  respiratory  organs.  If  the  medulla  is  severed 
from  the  portion  of  the  brain  lying  anterior  to  it  the  animal  con- 
tinues to  live  for  a  considerable  period.  The  respiratory  move- 
ments are  performed  rhythmically,  and  the  blood-vessels  retain 
their  tone  so  as  to  maintain  an  approximately  normal  blood-pressure. 
On  the  contrary,  destruction  of  the  medulla,  or  severance  of  its 
connections  with  the  underlying  parts,  is  followed  by  a  cessation 
of  respiration  and  a  loss  of  tone  in  the  arteries,  either  of  which 
results  in  the  rapid  death  of  the  organism  as  a  whole.  The  portions 
of  the  medulla  which  exercise  these  important  functions  are  desig- 
nated, respectively,  as  the  respiratory  and  the  vasomotor  or  vaso- 
constrictor centers.  Their  location  and  to  some  extent  their  con- 
nections have  been  determined  by  physiological  experiments,  but 
so  far  it  has  not  been  possible  to  mark  out  histologically  the  exact 
groups  of  cells  concerned.  The  position  and  physiological  properties 
of  these  centers  are  described  in  the  sections  on  respiration  and 
circulation.  These  centers  are  of  especial  importance  because  of 
their  wide  connections  with  the  body,  their  essentially  independent 
activity  in  reference  to  the  higher  parts  of  the  brain,  and  the  abso- 
lutely necessary  character  of  the  regulations  they  effect.  In  the 
development  of  the  brain  the  functions  originally  mediated  by  the 
lower  parts  have  been  transferred  more  and  more  to  the  higher 
parts,  especially  in  regard  to  conscious  sensation  and  motion,  and 
*  Bdrsiny,  "Wiener  Klin.  Wochenschrift,"  December  26,  1912. 


246  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

the  so-called  higher  psychical  activities.  But  the  unconscious  and 
involuntary  regulation  of  the  organs  of  circulation  and  respiration 
and  to  a  certain  extent  of  the  other  visceral  organs  has  been  cen- 
tralized, as  it  were,  in  the  medulla.  In  addition  to  the  control 
of  the  respiration  and  circulation  other  important  reflex  activities 
are  effected  through  the  medulla  by  means  of  the  vagus  nerve, 
which  has  its  nucleus  of  origin  in  this  part  of  the  brain.  Such,  for 
instance,  are  the  reflex  control  of  the  heart  through  the  cardio- 
inhibitory  center  and  of  the  motions  and  secretions  of  the  alimentary 
canal. 

The  Nuclei  of  Origin  and  the  Functions  of  the  Cranial 
Nerves. — The  origin,  course,  anatomical  and  physiological  relations 
of  the  first  or  olfactory,  second  or  optic,  and  eighth  or  auditory 
nerves  have  been  referred  to  in  the  preceding  pages.  For  the 
sake  of  completeness  the  origin  and  functions  of  the  other  cranial 
nerves  may  be  summarized  briefly  in  this  connection. 

The  Third  Cranial  Nerve  (N.  Oculomotorius) . — This  nerve  arises 
from  the  base  of  the  brain  on  the  median  side  of  the  corresponding 
pedunculus  cerebri.  It  is,  so  far  as  is  known,  only  a  motor  nerve, 
supplying  fibers  to  four  of  the  extrinsic  muscles  of  the  eyeballs — 
namely,  the  internal  rectus,  the  superior  rectus,  the  inferior  rectus, 
and  the  inferior  oblique — and  to  the  levator  palpebrse.  It  inner- 
vates also  two  important  intrinsic  muscles  of  the  eyeball,  the  ciliary 
muscle  used  in  accommodating  the  eye  in  near  vision,  and  the 
sphincter  of  the  iris,  which  controls  in  part  the  size  of  the  pupil. 
These  two  latter  muscles  belong  to  the  type  of  plain  muscle, 
and  the  fibers  of  the  third  nerve  which  innervate  them  terminate 
in  the  ciliary  ganglion,  whence  the  path  is  continued  by  sym- 
pathetic nerve  fibers  (postganglionic  fibers)  to  the  muscles.  In 
the  interior  of  the  brain  the  fibers  of  the  third  nerve  arise  from  a 
conspicuous  nucleus  or  collection  of  nuclei  situated  in  the  cen- 
tral gray  matter  of  the  midbrain  at  the  level  of  the  superior  col- 
liculus.  The  fibers  for  the  ciliary  muscle  and  sphincter  pupillae 
arise  more  anteriorly  than  those  for  the  extrinsic  muscles.  His- 
tologically  three  parts  at  least  may  be  distinguished,  as  shown  in 
Fig.  107,— namely,  the  lateral  (or  principal)  nucleus,  which  gives 
origin  chiefly  to  the  fibers  innervating  the  extrinsic  muscles;  the 
median  nucleus ;  and  the  nucleus  of  Edinger- Westphal.  According 
to  Bernheimer*  the  large  median  nucleus  gives  rise  to  the  fibers 
that  innervate  the  ciliary  muscles,  while  the  Edinger- Westphal 
nuclei  (accessory  nuclei)  control  the  movements  of  the  sphincter 
muscle  of  the  iris.  Some  of  the  fibers,  particularly  those  from 
the  lateral  nucleus  to  the  inferior  rectus,  the  internal  rectus,  and 

*  Bernheimer,  in  "Graefe-Saemisch's  Handbuch  der  ges.  Augenheilkunde," 
2d  ed.,  I,  41. 


Fig.  106. — Nuclei  of  origin  of  motor  and  primary  terminal  sensory  nuclei  of  cerebrrl 
nerves  (Held) :  Schematically  icpresented  in  a  supposedly  transparent  brain  stem  viewed 
from  behind.  (Nuclei  and  roots  of  motor  nerves  in  light  red,  of  sensory  nerves  in 
purple.  Cochlear  nerve  in  yellow.)  4,  nucleus  of  the  third  nerve  (n.  oculomotorii); 
5,  nucleus  of  the  fourth  nerve  (n.  trochlearis);  6,  the  fourth  nerve;  7,  the  descending 
(motor)  root  of  the  fifth  nerve;  8,  the  principal  motor  nucleus  of  the  fifth  nerve; 
9,  the  semilunar  ganglion  (g.  Gasseri);  26,  the  ascending  (sensory)  root  of  the  fifth 
nerve;  14,  nucleus  of  the  sixth  cranial  nerve;  15,  nucleus  of  the  facial  (seventh) 
nerve;  16,  the  facial  nerve;  34,  33,  nucleus  of  the  vestibular  branch  of  the  eighth  cranial 
nerve;  32,  ventral  nucleus  of  the  cochlear  branch  of  the  eighth  nerve;  27,  dorsal  nucleus 
of  the  cochlear  branch  of  the  eighth  nerve;  19,  29,  the  glossopharyngeal  nerve;  18,  28,  the 
Vagus  nerve;  20,  motor  nuclei  of  vagus  and  glossopharyngeal  (nucleus  ambiguus  and 
nucleus  dorsalis);  23,  24,  nucleus  of  the  ala?  cinerese,  the  solitary  bundle  and  its  nucleus: 
17,  the  eleventh  or  spinal  accessory  nerve;  22,  nucleus  of  the  spinal  accessory;  21,  nucleus 
of  the  hypoglossal  nerve. — (From  Spalteholz,  "Human  Anatomy.") 


CEREBELLUM,    PONS,    AND    MEDULLA. 


247 


the  inferior  oblique,  cross  the  mid-line  and  emerge  in  the  nerve 
of  the  opposite  side. 

The  Fourth  Cranial  Nerve  (N.  Trochlearis) . — This  nerve  emerges 
from  the  brain  in  the  anterior  medullary  velum  (valve  of  Vieussens) 
just  posterior  to  the  inferior  colliculus.  It  curves  around  the 
pedunculus  cerebri  to  reach  the  base  of  the  brain.  It  is  a  motor 
nerve,  and  supplies  fibers  to  the  superior  oblique  muscle  of  the 
eyeball.  In  the  interior  of  the  brain  the  fibers  arise  from  a 
nucleus  in  the  central  gray  matter  just  posterior  to  that  of  the 
third  nerve  (Fig.  107).  The  fibers  pass  dorsal  ward  toward  the 
velum  and  make  a  complete  decussation  before  emerging. 


Edinger-Westphal  nucleus. 
Principal  nucleus 
Median  nucleus. 


Nucleus  of  4th  nerve. 


Fig.  107. — Nuclei  of  origin  of  the  third  and  fourth  nerves. — (From  Poirier  and  Charpy.) 

The  Fifth  Cranial  Nerve  (N.  Trigeminus). — This  nerve  arises 
from  the  side  of  the  pons  by  two  roots,  a  small  motor  root,  portio 
minor,  and  a  large  sensory  root,  portio  major.  It  is,  therefore, 
a  mixed  motor  and  sensory  nerve,  supplying  motor  fibers  to  the 
muscles  of  mastication  and  sensory  fibers  of  pressure,  pain,  and 
temperature  to  the  face,  the  forepart  of  the  scalp,  the  eye,  nose, 
portions  of  the  ear,  mouth,  and  tongue,  and  to  the  dura  mater 
(Fig.  108).  In  the  interior  of  the  brain  the  motor  portion,  portio 
minor,  arises  partly  from  a  small  nucleus  in  the  pons  and  partly 
from  a  long  column  of  cells  extending  along  the  lower  margin  of  the 
central  gray  matter  throughout  the  midbrain.  This  column  and 
the  fibers  arising  from  it  constitute  the  descending  motor  root  of  the 


248 


PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 


fifth  nerve  (see  Fig.  109).    The  sensory  fibers  originate  from  the 
nerve  cells  in  the  Gasserian  ganglion  (g.  semilunare) .    The  branch 


Fig.  108. — Diagram 


showing  the  average  area  of  distribution  of  the  sensory  fibers  of  the 
trigeminal  nerve. — (Gushing.) 


N.  opht. 


N.  max.  eup. 


N.  max.  inf. 


Accessory 
;       motor 

nucleus. 
1 1 

Desc. 

motor 

root. 


Principal 
motor 


nucleus. 


Descending 
I         spinal  root. 


Fig.  109. — Nuclei  of  origin  of  the  fifth  cranial  nerve. — (From  Poirier  and  Charpy,  after 

Van  Gehuchten.) 

that  enters  the  brain  ends  partly  in  a  collection  of  cells  in  the  pons, 
the  so-called  sensory  nucleus,  and  partly  in  a  column  of  cells  extend- 
ing posteriorly  throughout  the  length  of  the  medulla.  These  ceils 


CEREBELLUM,    PONS,    AND    MEDULLA.  249 

and  the  fibers  ending  in  them  constitute  the  descending  spinal  root 
of  the  fifth  nerve  (see  Fig.  106). 

The  Sixth  Cranial  Nerve  (N.  Abducens). — This  nerve  arises  from 
the  base  of  the  brain  at  the  posterior  edge  of  the  pons.  It  is  a  motor 
nerve,  and  supplies  fibers  to  the  external  rectus  muscle  of  the  eye- 
ball. In  the  interior  of  the  brain  its  fibers  originate  in  a  small  spheri- 
cal nucleus  lying  beneath  the  floor  of  the  fourth  ventricle.  Con- 
nections have  been  traced  between  this  nucleus  and  the  pyramidal 
tract  of  the  opposite  side  (Fig.  106). 

The  Seventh  Cranial  Nerve  (N.  Facialis) . — This  nerve  appears 
on  the  base  of  the  brain  at  the  inferior  margin  of  the  pons,  lateral 
and  somewhat  posterior  to  the  emergence  of  the  sixth  nerve.  It 
is  mainly  a  motor  nerve,  but  carries  some  sensory  fibers  (fibers  of 
taste  and  general  sensibility)  received  through  the  n.  intermedius  of 
Wrisberg.  The  motor  fibers  of  the  nerve  supply  the  muscles  of  the 
face,  part  of  the  scalp,  and  the  ear,  including  its  intrinsic  muscles, 
and  in  addition  secretory  fibers  are  supplied  to  the  submaxillary 
and  sublingual  glands.  Within  the  brain  these  fibers  arise  from  a 
conspicuous  nucleus  in  the  tegmental  region  of  the  pons  lying 
ventral  to  the  nucleus  of  the  sixth,  beneath  the  middle  of  the  fourth 
ventricle  (Fig.  106) .  The  sensory  fibers  of  the  nerve  of  Wrisberg 
originate  in  the  nerve  cells  of  the  geniculate  ganglion. 

The  Ninth  Cranial  Nerve  (N.  Glossopharyngeus)  arises  from  the 
side  of  the  medulla, — the  restiform  body.  It  is  a  mixed  nerve, 
supplying  motor  fibers  to  the  muscles  of  the  pharynx  and  the  base 
of  the  tongue  and  secretory  fibers  to  the  parotid  gland.  Within 
the  brain  these  fibers  arise  from  two  motor  nuclei  common  to  this 
and  the  tenth  nerve, — namely,  a  dorsal  nucleus  below  the  floor  of 
the  fourth  ventricle  and  a  smaller  ventral  nucleus,  n.  ambiguus, 
in  the  reticular  substance  of  the  tegmentum  (Fig.  106).  The  sensory 
fibers  supply  in  part  the  mucous  membrane  of  the  tongue  and 
pharynx,  the  tympanic  cavity,  and  the  Eustachian  tube.  These 
fibers  arise  from  cells  in  the  two  ganglia  on  the  trunk  of  the  nerve, 
the  ganglion  superius  and  g.  petrosum.  The  branches  from  these 
cells  that  pass  into  the  medulla  terminate  in  the  nucleus  of  the  ala 
cinerea. 

The  Tenth  Cranial  Nerve  (N.  Vagus  or  Pneumogastricus) . — This 
nerve  arises  from  the  side  of  the  medulla  posterior  to  the  origin  of 
the  glossopharyngeal  nerve.  It  is  also  a  mixed  nerve,  with  an 
extensive  distribution  to  the  respiratory  and  digestive  organs  and 
the  heart.  Its  efferent  or  motor  fibers  arise  within  the  brain  from 
the  same  masses  of  cells  that  give  rise  to  the  motor  fibers  of  the 
glossopharyngeal.  These  fibers  supply  the  intrinsic  muscles  of  the 
larynx,  esophagus,  stomach,  small  intestine,  and  part  of  the  large 
intestine.  Inhibitory  fibers  are  carried  to  the  heart  and  secretory 


250  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

fibers  to  the  gastric  and  pancreatic  glands.  Its  sensory  or  afferent 
fibers  are  distributed  to  the  mucous  membrane  of  the  larynx, 
trachea,  and  lungs,  and  to  the  mucous  membrane  of  the  esophagus, 
stomach,  intestines,  and  gall-bladder  and  ducts.  These  fibers 
arise  from  cells  in  the  ganglia  on  the  trunk  of  the  nerve,  the  gan- 
glion jugulare  and  g.  nodosum.  The  branches  from  these  cells  that 
pass  into  the  medulla  terminate  in  the  gray  matter  of  the  ala  cinerea. 

The  Eleventh  Cranial  Nerve  (N.  Accessorius) . — This  nerve  is 
usually  described  as  arising  by  upper  roots  from  the  medulla,  and 
by  a  series  of  lower  roots  from  the  spinal  cord  as  low  as  the  fifth 
to  the  seventh  cervical  segment.  It  is  a  motor  nerve,  supplying 
fibers  to  the  sternomastoid  and  trapezius  muscles.  The  medullary 
branches  arise  from  the  posterior  portion  of  the  dorsal  motor 
nucleus  which  gives  origin  to  the  vagus,  while  the  spinal  branches 
originate  from  cells  in  the  anterior  horn  of  the  gray  matter  of  the 
cord  (Fig.  106). 

The  Twelfth  Cranial  Nerve  (N.  Hypoglossus). — This  nerve  arises 
from  the  medulla  in  the  furrow  between  the  anterior  pyramid  and 
the  olivary  body.  It  is  a  motor  nerve,  supplying  the  muscles  of 
the  tongue  and  the  extrinsic  muscles  of  the  larynx  and  hyoid  bone. 
Within  the  brain  these  fibers  originate  from  a  distinct  nucleus 
lying  in  the  floor  of  the  fourth  ventricle  near  the  mid-line  (Fig. 
106). 


CHAPTER  XII. 

THE   SYMPATHETIC   OR  AUTONOMIC  NERVOUS 
SYSTEM. 

The  chain  of  nerve  ganglia  extending  on  each  side  of  the  spinal 
column  to  the  coccyx  is  known  as  the  sympathetic  nervous  system. 
This  name  was  given  to  the  structure  under  the  misapprehension 
that  it  constitutes  a  nerve  pathway  through  which  so-called  sym- 
pathetic— or,  as  we  now  designate  them,  reflex  actions  of  distant 
organs  are  effected.  It  was  supposed  to  arise  from  the  brain  by 
branches  connected  with  the  fifth  and  sixth  cranial  nerves;*  We 
now  know  that  this  system  consists  of  a  series  of  ganglia  or  col- 
lections of  nerve  cells  connected  with  each  other  and  connected  also 
with  the  spinal  nerves.  Strictly  speaking,  the  term  sympathetic 
system  is  applicable  only  to  the  chain  of  ganglia  which  begins  with 
the  superior  cervical  ganglion  at  the  base  of  the  skull  and  ends 
with  the  ganglion  coccygeum.  There  are,  however,  other  outlying 
nerve  ganglia  with  or  without  specific  names  which  from  a  physio- 
logical and  indeed  from  an  anatomical  standpoint  belong  to  the  same 
group.  In  the  abdomen  we  have  the  so-called  prevertebral  gan- 
glia, the  celiac  ganglion,  from  which  arises  the  celiac  plexus,  the 
superior  mesenteric,  and  the  inferior  mesenteric  ganglion  giving 
rise  to  the  hypogastric  nerve.  These  ganglia  lie  ventral  to  the 
sympathetic  trunk,  but  are  in  direct  connection  with  it.  In  the 
head  region  the  ciliary,  sphenopalatine,  and  otic  ganglia  are 
also  of  the  same  type.  More  peripherally  are  numerous  other 
ganglia  lying  in  or  around  the  various  visceral  organs,  such  as  the 
submaxillary  ganglion  near  the  duct  from  the  corresponding  gland, 
the  cardiac  ganglia  in  the  heart,  and  the  extensive  system  of  nerve 
cells  in  the  walls  of  the  alimentary  canal  known  as  the  plexuses 
of  Meissner  and  Auerbach.  With  the  exception,  perhaps,  of  this 
last  system,  whose  histological  structure  and  connections  are  not 
satisfactorily  known,  all  of  these  ganglia  are  frequently  designated 
as  sympathetic,  and  from  a  physiological  as  well  as  an  anatomical 
standpoint  may  be  considered  with  the  ganglia  of  the  sympathetic 
trunk  or  chain.  Langley,  who  has  contributed  greatly  to  our 
knowledge  of  the  finer  anatomy  and  the  physiology  of  this  system, 
has  proposed  a  different  classification,  f 

*  Charles  Bell,  "The  Nervous  System  of  the  Human  Body,"  third  edi- 
tion, London,  1844,  p.  9. 

fSchafer's  "Text-book  of  Physiology,"  1900,  vol.  ii;  "Ergebnisse  der 
Physiologic,"  1903,  vol.  ii,  part  ii,  p.  823;  also  "Brain,"  1903,  vol.  xxvi,  and 
"Zentralblatt  f.  Physiologic,"  27,  149,  1913. 

251 


252 


PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 


Autonomic    Nervous    System. — According   to   Langley,    the 
efferent  fibers  from  the  nerve  cells  of  the  sympathetic  and  related 


PreqcuiqUonic -filre. 


iJJto, 

muscle. 


~Toat-qanolion.ic. 
J*n- 

Fig.  110.— Schema  to  show  the  general  relation  between 
the  preganglionic  and  postganglionic  fibers  of  the  autonomic 
paths. 

ganglia  supply  the  plain  muscle  tissues,  the 
cardiac  muscles,  and  the  glands, — that  is,  the 
organs  of  the  involuntary  or,  according  to  an 
old  nomenclature,  the  vegetative  processes  of 
the  body.  He  proposes  for  this  entire  system 
of  efferent  fibers  the  term  "autonomic,"  to  indi- 
cate that  they  possess  a  certain  independence 
of  the  central  nervous  system.  The  autonomic 
path  consists  of  two  neurons:  one  belonging  to 
the  central  nervous  system,  whose  axon  emerges 
in  one  of  the  spinal  or  cranial  nerves  and  ends 
around  the  dendrites  of  a  sympathetic  cell;  and 
one  occurring  in  some  one  of  the  numerous 
sympathetic  ganglia,  whose  axon  passes  to  the 
peripheral  tissue.  The  first  axon  is  spoken  of  as 
the  preganglionic  fiber,  the  second  as  the  post- 
ganglionic fiber.  Their  connections  are  repre- 
sented in  the  accompanying  schema  (Fig.  1 10) . 
Physiological  and  anatomical  investigations 
have  shown  that  autonomic  nerve-fibers  arise 
from  four  regions  in  the  central  nervous  system 
(Fig.  Ill):  First,  from  the  midbrain,  emerging 
in  the  third  cranial  nerve  and  passing  via  the 
ciliary  ganglion;  second,  from  the  bulbar  region, 
emerging  in  the  seventh,  ninth,  and  tenth 
cranial  nerves;  third,  from  the  thoracic  spinal 
nerves  (first  thoracic  to  fourth  or  fifth  lumbar) 
and  passing  in  general  via  the  ganglia  of  the 
sympathetic  chain;  fourth,  from  the  sacral 
region  by  way  of  the  so-called  nervus  erigens 
supplying  the  descending  colon,  rectum,  anus, 
and  genital  organs.  The  autonomic  fibers  at 


Fig.  111.— Illus- 
trating the  central  ori- 
gin of  the  autonomic 
fibers. — (Langley.) 


SYMPATHETIC    NERVOUS    SYSTEM.  253 

their  origin  in  the  central  nervous  system — that  is,  while  pre- 
ganglionic  fibers — are  all  possessed  of  a  small  medullated  sheath, 
having  a  diameter  of  1.8  to  4  /x.  The  postganglionic  fiber  is  in 
most  cases  non-medullated,  but  this  is  by  no  means  an  invariable 
rule.  In  many  cases  the  axons  from  sympathetic  cells  possess 
distinct,  although  small,  myelin  sheaths.  The  autonomic  fibers 
arising  from  the  midbrain,  bulb,  and  sacral  cord  are  distributed 
to  limited  parts  of  the  body,  while  those  from  the  thoracic  part 
of  the  cord,  the  great  sympathetic  system,  innervate  practically 
all  regions  of  the  body.  In  their  physiological  and  pharmacological 
reactions  the  two  groups  offer  certain  contrasts,  which  have  been 
much  emphasized  in  recent  years.  For  this  and  other  reasons, 
Langley  has  suggested  a  comprehensive  classification  based  on 
anatomical  grounds  which  is  illustrated  in  the  following  schema: 

Autonomic. 


Parasympathetic.  Sympathetic.          Enteric. 


Ocular.  Oro-anal. 


Tectal  Bulbar  Sacral  Thoracic 

auto-       autonomies.  autonomies.       autonomies, 

nomics. 

The  enteric  group  comprises  the  system  forming  the  extensive 
plexuses  of  Auerbach  and  Meissner.  We  know  but  little  in  regard 
to  the  anatomical  connections  of  these  plexuses  with  the  central 
nervous  system,  or  the  peculiarities  of  their  functional  activity; 
therefore,  provisionally,  they  are  set  aside  as  a  separate  group. 
The  grouping  of  the  remaining  autonomic  fibers  into  two  great 
classes — sympathetic  and  parasympathetic — may  or  may  not 
come  into  general  use,  but  the  division  of  the  entire  system,  with 
the  exception  of  the  enteric  fibers,  into  the  four  varieties  of  auto- 
nomies, tectal,  bulbar,  thoracic,  and  sacral,  according  to  their 
point  of  emergence  from  the  central  nervous  system,  affords  a 
useful  basis  for  physiological  description.  Unfortunately,  in 
pharmacological  and  medical  literature  a  variation  in  this  nomen- 
clature has  been  adopted  by  some  writers,  who  use  the  word 
autonomic  in  a  narrower  sense  to  designate  the  fibers  grouped 
under  the  term  "parasympathetic"  in  the  above  schema. 

The  Nicotin  Method. — The  course  of  the  autonomic  fibers 
has  been  traced  in  many  cases  to  their  corresponding  sympathetic 


254  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

nerve  cells  partly  by  the  method  of  secondary  degeneration  and 
partly  by  the  use  of  nicotin,  as  first  described  by  Langley  and 
Dickinson.*  These  authors  have  shown  that  after  the  use  of 
nicotin,  either  injected  into  the  circulation  or  painted  upon  the 
ganglion,  stimulation  of  the  preganglionic  fiber  in  any  part  of  its 
course  fails  to  give  any  response,  while  stimulation  of  the  post- 
ganglionic  fiber,  on  the  contrary,  is  still  effective.  It  would  seem, 
therefore,  that  the  nicotin  paralyzes  the  connection  (the  synapse) 
of  the  preganglionic  fiber  with  the  sympathetic  nerve  cell,  and  by 
means  of  the  local  application  of  the  drug  it  is  possible  in  many 
cases  to  pick  out  the  ganglion  in  which  the  preganglionic  fiber  really 
ends.  For  it  often  happens  that  in  the  sympathetic  trunk  a 
preganglionic  fiber  will  pass  through  several  ganglia  before 
making  final  connections  with  a  sympathetic  cell.  So  far,  the 
course  of  these  fibers  has  been  traced  most  successfully  in  the 
case  of  the  nerves  supplying  the  sweat-glands,  blood-vessels,  and 
especially  the  erector  muscles  of  the  hairs,  the  so-called  pilomotor 
nerve-fibers.  The  visible  result  of  stimulation  in  the  last  case 
gives  a  ready  means  of  determining  the  presence  of  the  fibers. 

General  Course  of  the  Autonomic  Fibers  Arising  from  the 
Spinal  Cord — Thoracic  Autonomies. — It  has  long  been  known 
that  the  spinal  nerves  are  connected  with  many  of  the  ganglia  of  the 
sympathetic  chain  by  fine  branches  known  as  the  rami  communi- 
cantes.  In  the  thoracic  and  lumbar  regions  (first  thoracic  to  second 
or  fourth  lumbar)  these  rami  consist  of  two  parts,  a  white  and  a 
gray  ramus,  the  difference  in  color  being  due  to  the  fact  that  the 
white  rami  are  composed  almost  entirely  of  medullated  fibers, 
while  the  gray  rami  are  largely  non-medullated.  In  the  cervical, 
lower  lumbar,  and  sacral  regions  the  rami  consist  only  of  the  gray 
part.  Physiological  experiments  show  that  the  white  rami  consist 
of  preganglionic  fibers  that  arise  from  nerve  cells  in  the  spinal  cord, 
pass  out  by  way  of  the  anterior  roots,  enter  the  white  ramus,  and 
thus  reach  the  sympathetic  chain.  On  entering  this  latter  the  fiber 
may  not  end  at  once  in  the  ganglion  at  which  it  enters,  but  may  pass 
up  or  down  in  the  chain  for  some  distance.  Eventually,  however,  it 
ends  around  a  sympathetic  nerve  cell  and  the  path  is  then  con- 
tinued by  the  axon  from  this  cell  as  the  postganglionic  fiber.  The 
gray  rami  consist  of  these  latter  fibers,  which  return  from  the  sym- 
pathetic chain  to  the  spinal  nerves  and  are  then  distributed  to  the 
areas  supplied  by  these  nerves,  particularly  the  cutaneous  areas, 
since  the  skin  branches  are  the  ones  that  supply  the  sweat  glands, 
the  blood-vessels,  and  the  erector  muscles  of  the  hairs.  It  will  be 
noted  that  the  fibers  that  pass  from  a  given  spinal  nerve — say,  the 
twelfth  thoracic — by  a  white  ramus  to  enter  the  sympathetic  chain 
*  "Proceedings,  Royal  Society,"  1889,  46,  423. 


SYMPATHETIC    NERVOUS    SYSTEM.  255 

do  not  return  as  postganglionic  fibers  by  the  gray  ramus  to  the 
same  spinal  nerve.  On  the  contrary,  the  gray  ramus  of  the  twelfth 
thoracic  may  consist  of  the  postganglionic  portion  of  autonomic 
fibers  that  enter  the  sympathetic  through  a  white  ramus  of 
one  of  the  higher  thoracic  nerves.  In  general,  we  may  say 
that  there  is  a  great  outflow  of  autonomic  fibers,  including 
vasomotor,  sweat,  and  pilomotor  fibers,  in  the  white  rami  commu- 
nicantes  from  the  first  or  second  thoracic  to  the  second  or  fourth 
lumbar  nerves.  Those  of  these  fibers  that  are  to  be  distributed  to 
the  skin  areas  of  the  body — head,  limbs,  and  trunk — return  by  way 
of  the  gray  rami  to  the  various  spinal  nerves  and  are  distributed  with 
these  nerves,  the  distribution  being  somewhat  different  in  different 
animals  and  for  the  several  varieties  of  fibers.  Those  fibers  that 
are  distributed  eventually  to  the  blood-vessels,  glands,  and  walls 
of  the  viscera  have  a  different  course  from  those  supplying  the 
glands,  blood-vessels,  and  plain  muscle  of  the  head  region.  For 
the  head  region  the  fibers  after  entering  the  sympathetic  chain  pass 
upward  along  the  cervical  sympathetic  to  end  in  the  superior 
cervical  ganglion;  thence  the  path  is  continued  by  postganglionic 
fibers  which  emerge  by  the  various  plexuses  that  arise  from  this 
ganglion.  For  the  abdominal  and  pelvic  viscera  the  fibers  (particu- 
larly the  rich  supply  of  vasoconstrictor  fibers),  after  entering  the 
sympathetic  chain,  emerge,  still  as  preganglionic  fibers,  by  the 
splanchnic  nerves  that  run  to  the  celiac  ganglia  or  in  the  branches 
connecting  with  the  inferior  mesenteric  ganglia,  and  then  become' 
postganglionic  fibers  (see  Fig.  112).  The  details  of  the  course  of 
the  vasomotor,  sweat,  visceromotor  fibers  to  the  different  regions, 
the  cardiac  fibers,  etc.,  will  be  given  in  the  appropriate  sections. 

General  Course  of  the  Autonomic  Fibers  Arising  from  the 
Brain — Tectal  and  Bulbar  Autonomies. — These  fibers  leave 
the  brain  in  the  third,  seventh,  ninth,  tenth,  and  eleventh  cranial 
nerves.  Those  that  emerge  in  the  third  nerve  end,  as  preganglionic 
fibers,  in  the  ciliary  ganglion.  Their  postganglionic  fibers  leave 
this  ganglion  in  the  short  ciliary  nerves  and  innervate  the  plain 
muscle  of  the  sphincter  of  the  iris  and  the  ciliary  muscle.  The 
fibers  that  emerge  in  the  seventh  and  ninth  nerves  probably  supply 
the  glands  and  blood-vessels  (vasodilator  fibers)  of  the  mucous 
membrane  of  the  nose  and  mouth.  Some  of  these  fibers  reach  the 
fifth  nerve  by  way  of  anastomosing  branches  and  are  distributed 
with  it.  Their  preganglionic  portion  terminates  in  some  of  the 
ganglia  belonging  to  the  sympathetic  type  which  are  found  in  this 
region,  such  as  the  sphenopalatine  and  otic  ganglia,  and  the  sub- 
maxillary  and  sublingual  ganglia  for  the  fibers  distributed  to  the 
glands  of  the  same  name.  The  autonomic  fibers  that  arise  with 
the  tenth  (and  the  eleventh)  nerves  are  distributed  through  the 


256 


PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 


vagus.     Physiologically  these  fibers 


Fig.  112. — Diagram  giving  a  schematic 
representation  of  the  course  of  the  autonomic 
(sympathetic)  fibers  arising  from  the  thoraci co- 
lumbar  and  sacral  regions  of  the  cord.  The 
preganglionic  fiber  is  represented  in  red,  the 
ppstganglionic  in  black  lines.  The  arrows  in- 
dicate the  normal  direction  of  the  nerve  im- 
pulses or  nerve  conduction.  S.c.,  Superior 
cervical  ganglion;  I.e.,  inferior  cervical  gan- 
glion; T,  the  first  thoracic  ganglion;  Sp.t  the 
splanchnic  nerve;  C.,  the  semilunar  or  celiac 
ganglion ;  TO.,  the  inferior  mesenteric  ganglion ; 
A.,  the  hypogastric  nerves;  N.E.,  the  nervus 
erigens.  The  numerals  indicate  the  corre- 
sponding spinal  nerves. 


consist  of  motor  fibers  (viscero- 
motor  fibers)  to  the  mus- 
culature of  the  esophagus, 
stomach,  and  small  intestine, 
motor  fibers  to  the  bron- 
chial musculature,  inhibitory 
fibers  to  the  heart,  and  secre- 
tory fibers  to  the  gastric  and 
pancreatic  glands.  The  gan- 
glia in  which  the  pregangli- 
onic portions  end  have  not 
been  definitely  located,  but 
probably  they  comprise  the 
small  and,  for  the  most  part, 
unnamed  local  ganglia  found 
in  or  near  the  organs  inner- 
vated. 

General  Course  of  the  Au- 
tonomic Fibers  Arising  from 
the  Sacral  Cord — Sacral  Auto- 
nomies.— The  autonomic  fibers 
of  this  region  emerge  from  the 
cord  in  the  anterior  roots  of 
the  sacral  nerves, — second  to 
fourth.  The  branches  from 
these  roots  unite  to  form  the 
so-called  nervus  erigens  (pelvic 
nerve),  which  loses  itself  in  the 
pelvic  plexus  without  making 
connections  with  the  sympa- 
thetic chain  of  ganglia.  The 
pelvic  plexus  is  formed  in  part 
also  from  the  hypogastric 
nerve  arising  from  the  inferior 
mesenteric  ganglion.  Through 
this  latter  path  thoracic  auto- 
nomic fibers  from  the  upper 
lumbar  region  enter  the  plexus 
(Fig.  112).  The  autonomic 
fibers  of  the  nervus  erigens 
supply  vasodilator  fibers  to  the 
external  genital  organs,  and  in 
the  male  constitute  the  nervous 
part  of  the  physiological  mech- 
anism for  erection,  whence  the 


SYMPATHETIC    NERVOUS    SYSTEM.  257 

name.  They  suppty,  also,  vasodilator  fibers  to  rectum  and  anus 
and  motor  fibers  to  the  plain  muscles  of  the  colon,  rectum,  and 
anus.  The  preganglionic  parts  of  these  fibers  end  in  small  sympa- 
thetic ganglia  in  the  pelvic  plexus  or  in  the  neighborhood  of  the 
organs  supplied. 

Normal  Mode  of  Stimulation  of  the  Autonomic  Nerve  Fibers. 
— In  distinction  from  the  nerve  fibers  innervating  the  skeletal 
muscles  practically  the  whole  set  of  autonomic  fibers  is  removed 
from  the  control  of  the  will.  An  apparent  exception  to  this  general 
statement  is  found  in  the  fact  that  the  ciliary  muscle  of  the  eye  is 
seemingly  under  voluntary  control.  We  must  suppose  that  under 
normal  conditions  the  autonomic  fibers  are  always  excited 
reflexly,  and  the  course  of  the  afferent  fibers  concerned  in  these 
reflexes  and  the  nature  of  the  effective  sensory  stimulus  in 
each  case  are  important  in  the  consideration  of  each  of  the 
physiological  mechanisms  involved.  Most  of  these  mechanisms, 
as  we  shall  find,  work  reflexly — that  is,  without  voluntary 
initiation — and,  for  the  most  part,  unconsciously,  for  instance, 
the  movements  of  the  intestines,  the  secretion  of  the  digestive 
glands,  and  the  contraction  and  dilatation  of  the  arteries. 
The  autonomic  nerve-fibers  control,  therefore,  the  uncon- 
scious co-ordinated  actions,  the  so-called  vegetative  processes, 
of  the  body.  There  is  no  apparent  reason  in  the  anatomical  ar- 
rangements why  these  fibers  should  be  free  from  voluntary  control. 
Their  distinguishing  characteristic  in  comparison  with  the  nerves 
for  the  voluntary  movements  is  the  fact  that  they  all  terminate 
first  in  sympathetic  nerve  cells;  but  this  fact  gives  no  explanation 
of  the  absence  of  conscious  control  by  the  will.  We  are  justified  in 
saying  that  nerve  paths  that  pass  through  sympathetic  nerve  cells 
cannot  be  excited  voluntarily;  but  the  immediate  reason  for  this 
fact  is  probably  to  be  found  in  the  ultimate  point  of  origin  of  these 
paths  in  the  central  nervous  system.  What  we  designate  as  vol- 
untary motor  paths  arise  in  a  definite  region  of  the  cortex, — the 
motor  area  in  the  frontal  lobe.  Our  motor  conceptions  or  ideas 
can  affect  the  efferent  paths  arising  in  this  region,  but  not  those, 
apparently,  which  originate  in  other  parts  of  the  brain.  On  the 
other  hand,  much  recent  work*  has  emphasized  the  important  fact 
that  strong  emotional  states,  such  as  fear,  anger,  joy,  etc.,  stimulate 
the  autonomic  system,  giving  rise  to  changes  in  the  heart-rate, 
blood-pressure  and  internal  secretions,  and  causing  movements  of 
the  bowels,  bladder,  etc. 

*  See  Cannon,  "Bodily  Changes  in  Pain,"  etc.,  1915. 
17 


CHAPTER  XIII. 
THE  PHYSIOLOGY  OF  SLEEP. 

The  state  of  more  or  less  complete  unconsciousness  which  we 
designate  as  sleep  forms  a  part  of  the  physiology  of  the  brain  which 
naturally  has  attracted  much  attention,  and  the  theoretical  explana- 
tions that  have  been  advanced  at  one  time  or  another  are  exceed- 
ingly numerous.  The  same  condition  occurs  in  many,  if  not  all,  of 
the  other  mammalia,  and,  indeed,  in  all  living  things  there  occur 
periods  of  rest  alternating  with  periods  of  activity.  Whether  these 
periods  of  rest  are  essentially  similar  in  nature  to  sleep  in  man 
is  a  question  in  general  physiology  that  can  be  solved  only  when 
we  know  more  of  the  chemistry  of  living  matter.  Within  the  human 
body  there  are  other  tissues  that  exhibit  periods  of  rest  alternating 
with  periods  of  activity, — the  gland  cells,  for  example.  The  secret- 
ing cells  of  the  pancreas  have  a  period  of  activity  in  which  the 
destructive  processes  exceed  the  constructive,  and  a  period  of  rest 
in  which  these  relations  are  reversed.  We  may  compare  this  con- 
dition in  the  gland  cells  with  that  in  the  brain.  Sleep,  from  this 
standpoint,  is  a  period  of  comparative  rest  or  inactivity,  during 
which  the  constructive  or  anabolic  processes  are  in  excess  of  the 
disassimilatory  changes.  The  period  of  sleep  is  a  period  of  re- 
cuperation, and  doubtless  all  tissues  have  these  alternating 
phases.  To  explain  sleep  fundamentally,  therefore,  it  would  be 
necessary  to  understand  the  chemical  changes  of  anabolism  and 
catabolism,  and  an  explanation  of  the  sleep  of  the  brain  tissues 
would  doubtless  explain  the  similar  phenomenon  in  other  tissues. 
But  what  the  physiologists  desire  first,  and  have  attempted  to 
determine,  is  an  explanation  of  why  this  condition  comes  on  with 
a  certain  periodical  regularity, — an  explanation,  in  other  words,  of 
the  mechanism  of  sleep,  the  change  or  changes  in  the  brain  or  the 
body  which  reduce  the  metabolism  of  the  brain  tissue  to  such 
an  extent  that  it  falls  below  the  level  necessary  to  cause  conscious- 
ness. 

Physiological  Relations  during  Sleep. — The  central  and  most 
important  fact  of  sleep  is  the  partial  or  complete  loss  of  conscious- 
ness, and  this  phenomenon  may  be  referred  directly  to  a  lessened 
metabolic  activity  in  the  brain  tissue,  presumably  hi  the  cortex 
cerebri.  During  sleep  the  following  changes  have  been  recorded: 

258 


THE    PHYSIOLOGY    OF    SLEEP.  259 

The  respirations  become  slower  and  deeper  and  the  costal  respiration 
(respiration  by  elevation  of  the  ribs)  predominates  over  the  ab- 
dominal or  diaphragmatic  respiration  as  compared  with  the  waking 
condition.  The  respiratory  movements  also  show  frequently  a 
tendency  to  become  periodic, — that  is,  to  increase  and  decrease 
regularly  in  groups  after  the  manner  of  the  Cheyne-Stokes  type 
of  breathing.  The  expiration  is  frequently  shorter  and  more  audi- 
ble than  in  the  respirations  of  the  waking  hours.  The  eyeballs 
roll  upward  and  outward  and  the  pupil  is  constricted.  According 
to  Lombard's  observations,  the  knee-kick  decreases  or  disappears 
entirely  during  sleep.  Some  of  the  constant  secretions  are  dimin- 
ished in  amount, — as,  for  instance,  the  urine,  the  tears,  and  the 
secretion  of  the  mucous  glands  in  the  nasal  or  pharyngeal  mem- 
brane. One  of  the  familiar  signs  of  a  sleepy  condition  is  the  dryness 
of  the  surface  of  the  eyes,  a  condition  that  leads  to  the  rubbing 
of  the  eyes.  It  is  sometimes  stated  that  the  digestive  secretions 
are  diminished  during  sleep,  but  the  statement  does  not  seem  to 
rest  upon  satisfactory  observations,  and  may  be  doubted.  The 
pulse-rate  decreases  during  sleep,  the  blood-pressure  falls  some- 
what, and  there  are  certain  significant  changes  in  the  distribution  of 
blood  in  the  body.  These  latter  changes  will  be  referred  to  more 
in  detail  below.  The  physiological  oxidations  are  also  decreased, 
as  shown  by  the  diminished  output  of  carbon  dioxid.  On  the 
whole,  however,  the  physiological  activities  of  the  body  go 
on  much  as  in  the  waking  condition.  Those  changes  in  ac- 
tivity that  do  occur  are,  in  the  main,  an  indirect  result  of  the 
partial  or  complete  cessation  of  activity  in  the  cerebrum.  One 
might  say  that  while  the  cortex  of  the  brain  sleeps — that  is,  is 
inactive — most  of  the  other  organs  of  the  body  may  be  awake  and 
maintain  their  normal  activity.  Another  fact  of  interest  is  that 
the  entire  cortex  does  not  fall  asleep  at  the  same  instant  nor 
always  to  the  same  extent.  Ordinarily  as  sleep  sets  in  the  power 
to  make  conscious  movements  is  lost  first  and  the  auditory  sen- 
sibility last,  and  on  awakening  the  reverse  relation  holds.  The 
individual  may  be  conscious  of  sound  sensations  before  he  is 
sufficiently  awake  to  make  voluntary  movements. 

The  Intensity  of  Sleep. — The  intensity  of  sleep — that  is,  the 
depth  of  unconsciousness — has  been  studied  by  the  simple  device 
of  ascertaining  the  intensity  of  the  sensory  stimulus  necessary  to 
awaken  the  sleeper.  Kohlschiitter  *  used  for  this  purpose  a  pendu- 
lum  falling  against  a  sounding  plate.  At  intervals  of  a  half-hour 
during  the  period  of  sleep  the  auditory  stimuli  thus  produced  were 
increased  in  intensity  until  waking  was  caused.  His  results  are 
expressed  in  the  curve  shown  in  Fig.  113,  in  which  the  intensity 
*  Kohlschiitter,  "Zeitschrift  f.  rationelle  Medicin,"  1863. 


260 


PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 


of  the  sleep  is  represented  by  the  height  of  the  ordinates.  Accord- 
ing to  this  curve,  the  greatest  intensity  is  reached  about  an  hour 
after  the  beginning,  and  from  the  second  to  the  third  hour  onward 
the  depth  of  sleep  is  very  slight;  the  activities  of  the  brain  lie  just 
below  the  threshold  of  consciousness.  It  appears  also  from  this 
curve  that  the  recuperative  effect  of  sleep  is  not  proportional  to 
its  intensity.  The  long  period  from  the  third  to  the  eighth  hour, 
in  which  the  depth  of  sleep  is  so  slight  is  presumably  as  important 
in  restoring  the  brain  to  its  normal  waking  irritability  as  the  deepei 


STRENGTH  OF  STIMULUS 
800 


HOURS  QS     10      L$    20     2.5    3.0    3.5     4.0    45     SO    5.5    &0 


70    75   7.8 


Fig.  113.— Curve  illustrating  the  strength  of  an  auditory  stimulus  (a  ball  falling  from 
a  height)  necessary  to  awaken  a  sleeping  pers9n.  The  hours  marked  below.  The  testa 
were  made  at  half-hour  intervals.  The  curve  indicates  that  the  distance  through  which 
it  was  necessary  to  drop  the  ball  increased  during  the  first  hour,  and  then  diminished,  at 
first  very  rapidly,  then  slowly. — (Kohlschiitter.) 

period  up  to  the  third  hour.  That  this  is  the  case  is  perhaps 
sufficiently  demonstrated  by  the  experience  of  every  one,  but 
Weygandt  has  attempted  to  prove  the  point  by  direct  experi- 
ments. He  found  that  for  simple  mental  acts,  such  as  the  ad- 
dition of  pairs  of  figures,  a  short  sleep  was  as  effective  as  a  longer 
one,  but  for  more  difficult  mental  work,  such  as  memorizing 
groups  of  ten  figures,  efficiency  was  distinctly  improved  in 
proportion  to 'the  length  of  sleep.  It  is  probable  that  the  curve 
of  intensity  of  sleep  varies  somewhat  with  the  individual  and 
also  with  surrounding  conditions.  That  individual  variations 
occur  is  indicated  by  the  results  obtained  by  two  other  observers, 
Monninghoff  and  Piesbergen,*  who  used  the  same  general 
method  as  was  employed  by  Koklschiitter.  The  sleeper  was 
awakened  by  auditory  stimuli  produced  by  dropping  a  lead 
*  Monninghoff  and  Piesbergen,  "  Zeitschrift  f.  Biologic,"  19,  1,  1883. 


THE    PHYSIOLOGY    OF    SLEEP.  261 

ball  from  varying  heights  upon  a  lead  plate.  Only  two  experi- 
ments were  made  each  night,  and  the  curves  constructed  repre- 
sent, therefore,  composites  from  several  periods  of  sleep.  One 
of  the  curves  obtained  is  represented  in  Fig.  114.  According 
to  this  curve  the  maximum  intensity  is  reached  between  the 
first  and  second  hours,  and  between  the  fourth  and  the  fifth 
hour  there  is  a  second  slight  increase  in  intensity,  giving  a 
second  maximum  in  the  curve.  This  latter  feature  of  a  second 
increase  in  intensity  toward  morning  is  very  apparent  also  in 
some  interesting  curves  obtained  by  Czerny  from  children  of 
different  ages.  His  method  of  awakening  the  sleeper  was  to  use 
induction  shocks  of  varying  intensities.  In  children  of  four 
years  with  a  normal  period  ,of  sleep  of  about  twelve  hours  the 
curve  shows  a  very  marked  increase  in  intensity  toward  morning, 
as  shown  in  Fig.  115.  Curves  made  by  similar  experimental 
methods  are  reported  by  Howell  and  by  Michelson.*  The 
striking  feature  about  all  the  curves  is  the  sharp  increase  in 
intensity  shortly  after  falling  asleep;  in  most  cases  the  maximum 
is  reached  at  the  first  or  second  hour  of  slumber,  but  Michelson 
believes  that  there  are  two  classes  of  individuals  in  this  respect, 
those  with  morning  dispositions  in  whom  the  maximum  of 
mental  efficiency  occurs  early  in  the  day  and  who  upon  going  to 
sleep  show  a  maximum  of  intensity  within  an  hour,  and  those 
with  evening  dispositions  whose  maximum  efficiency  comes 
later  in  the  day  and  whose  curve  of  sleep  reaches  its  maximum 
of  intensity  with  relative  slowness  (1J  to  3£  hrs.). 

Changes  in  the  Circulation  during  Sleep. — That  the  circula- 
tion undergoes  distinct  and  characteristic  changes  during  sleep 
has  been  shown  upon  man  by  phlethysmographic  observations  and 
upon  the  lower  animals  by  direct  kymographic  experiments. 
Using  very  young  dogs,  Tarchanofff  has  been  able  to  measure 
their  blood-pressure  while  sleeping.  He  finds  that  the  pressure 
in  the  aorta  falls  by  an  amount  equal  to  twenty  to  fifty  millimeters 
of  mercury  during  sleep,  and  that  the  same  general  fact  is  true 
for  man  is  shown  by  the  sphygmomanometric  observations  reported 
by  Brush  and  Fayerwreather.J  Making  use  of  patients  with  a 
trephine  hole  in  the  skull,  Mosso§  found  that  during  sleep  the 
volume  of  the  brain  diminishes,  while  that  of  the  arm  or  foot 
increases.  The  apparent  explanation  of  this  fact  is  that  the 
blood-vessels  in  the  body  dilate,  and  receive,  therefore,  more 

*  Howell,  "Journal  of  Experimental  Medicine,"  2,  313,  1897.  Michel- 
son,  "Dissertation,"  Dorpat,  1891. 

fTarchanoff,  "Archives  italiennes  de  biologic,"  21,  318,  1894. 

j  Brush  and  Fayerweather,  "American  Journal  of  Physiology,"  5,  199, 
1901. 

§  Moaso,  "Ueber  den  Kreislauf  des  Blutes  im  menschlichen  Gehirn,"  1881. 


262 


PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 


MS  J      SJS    £30  S4S  b-IS 


Fig.  114. — Curve  of  intensity  of  sleep  according  to  Monninghoff  and  Piesbergen.  The 
figures  along  the  abscissa  represent  time  in  hours  from  the  beginning  of  sleep;  those  along 
the  prdinate  the  relative  intensity  of  sleep  measured  in  milligram-millimeters,  expressing 
(he  intensity  of  sound  of  a  falling  body  necessary  to  awaken  the  sleeper. 


Fig.  115. — Curve  of  intensity  of  sleep  in  a  child  of  three  years  and  eight  months,  as  deter* 

mined  by  Czerny. 


THE    PHYSIOLOGY    OF    SLEEP. 


263 


blood,  while  a  smaller  amount  flows  to  the  brain.  The  volume  of 
the  foot  or  hand  was  measured  in  these  experiments  by  incasing 
it  in  a  plethysmograph  (see  section 
on  Circulation) .  Unfortunately,  this  re-  2 
suit  has  been  contradicted  by  other  J- 
observers,*  who  claim  that  during  sleep  ? 
there  is  a  vascular  dilatation  in  the  brain  5 
as  well  as  in  the  limbs.  In  view  of  this  £ 
contradiction  in  results  between  experi-  | 
menters  making  use  of  similar  methods  w 
of  work,  it  is  evident  that  theories,  such  •§ 
as  are  described  below,  which  are  based  ° 
upon  a  diminution  in  blood-flow  through 
the  brain,  are  brought  intb  question.  * 
More  extensive  observations  upon  in- 
dividuals with  an  opening  in  the  skull-  H. 
wall  are  greatly  needed  to  determine  this  & 
point.  The  author  f  has  extended  Mos-  g' 
so's  observations  so  as  to  obtain  a  pleth-  £• 
ysmographic  record  of  the  volume  of  the  "? 
hand  and  part  of  the  forearm  during  H 
a  period  of  normal  sleep.  One  of  the 
records  thus  obtained  is  given  in  Fig. 
116.  The  amount  of  dilatation  is  |- 
given  by  the  ordinates  below  the  base  ^ 
line.  Granting  that  the  increase  in  £ 
volume  of  the  hand  and  arm  is  caused  » 
by  an  increase  in  the  volume  of  blood  » 
contained  in  their  blood-vessels,  the  | 
curve  shows  that  during  and  after 
the  onset  of  sleep  the  blood-vessels  in  | 
the  arm  slowly  dilate  until  between  g" 
one  and  two  hours  after  the  begin- 
ning of  sleep.  After  this  maximum  g 
is  reached  the  arm  remains  more  or  > 
less  of  the  same  volume  for  a  certain  ? 
period  or  else  diminishes  in  volume 
very  gradually.  Shortly  before  waking,  g 
however,  the  arm  begins  to  diminish  > 
more  rapidly  in  size,  owing,  doubtless,  * 
to  the  contraction  of  its  blood-vessels; 
so  that  at  the  time  of  awaking  it  has  practically  the  same  volume  as 
at  the  beginning  of  sleep.  If,  on  the  basis  of  Mosso's  experiments, 

*Shepard,  "American  Journal  of  Physiology,"  23,  1909  ("Proc.  Amer. 
Physiol.  Soc.");  Brodmann,  "Journal  f.  Psychologie  u.  Neurologic,"  1,  10, 


1902. 


t  Howell,  loc.  cit. 


264 


PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 


we  assume  that  the  blood-flow  in  the  brain  stands  in  a  reciprocal  re- 
lation to  that  in  the  arm,  this  curve  may  be  taken  to  indicate  that 
before  and  after  the  onset  of  sleep  the  blood-flow  through  the 
brain  diminishes  rapidly  to  a  certain  point  and  that  before 
awaking  the  blood-flow  begins  to  increase  again  until  it  reaches 
normal  proportions. 

Effect  of  Sensory  Stimulation. — That  sensory  stimuli  of  vari- 
ous kinds  affect  a  sleeping  individual  without  entirely  awaking 
him  is  shown  by  the  movements  that  may  be  caused  in  this 
way,  and  also  by  the  nature  of  the  dreams  which  may  be  pro- 
voked. It  is  very  interesting  to  find  from  plethysmographic 
observations  that  all  kinds  of  sensory  stimulations  from  without 
and  from  within  are  liable  to  affect  the  circulation  of  the  blood 
during  sleep.  As  shown  by  the  plethysmograph,  the  volume  of 


Fig.  117. — Sleep:  A,  effect  of  external  impression  (music  box),  insufficient  to  awaken 
sleeper, — a  marked  diminution  in  volume  of  the  arm ;  B,  effect  of  external  impression 
(music  box)  sufficient  to  awaken  sleeper;  a  stronger  diminution  in  volume  followed  by 
dilatation  as  the  subject  again  fell  asleep. 

the  arm  diminishes  more  or  less  in  proportion  to  the  intensity 
of  the  stimulus,  and  the  probable  interpretation  of  this  fact  is 
that  the  sensory  stimulus  acts  reflexly  upon  the  vasomotor 
center  in  the  medulla  and  causes  through  it  a  contraction  of 
the  blood-vessels.  In  the  curve  shown  in  Fig.  116  most  of 
the  irregularities  were  traceable  to  causes  of  this  kind, — noises 
in  the  building  or  street  or  other  sensory  stimuli.  The  same 
fact  is  exhibited  in  a  striking  way  by  the  curves  given  in  Fig. 
117.  In  these  experiments  the  recorder  attached  to  the  plethys- 


THE    PHYSIOLOGY    OF    SLEEP.  265 

mograph  to  register  the  changes  in  volume  was  of  a  different 
kind  (tambour)  and  the  record  reads  in  a  reverse  way  to  that 
shown  in  Fig.  lib, — that  is,  a  dilatation  is  recorded  by  a  rise  in 
the  curve  and. a  constriction  by  a  fall.  The  recorder  being  more 
sensitive,  the  volume  changes  in  the  arm  due  to  the  heart  beat  are 
clearly  indicated.  The  legends  attached  to  the  illustration  explain 
the  results  of  the  experiments. 

Theories  of  Sleep. — Many  hypotheses  have  been  advanced 
to  explain  the  nature  and  causation  of  sleep.*  Confining  ourselves 
to  the  more  recent  hypotheses  that  attempt  to  explain  the  immedi- 
ate cause  of  the  production  of  the  condition,  the  following  brief  de- 
scription will  suffice  to  show  the  nature  of  the  theories  proposed: 

1.  The  Accumulation  of  Acid  Waste  Products. — Prey  erf  and 
also  Obersteiner  have  suggested  that  the  accumulation  of  acid 
waste  products  in  the  blood  brings  on  a  gradually  increasing  loss  of 
irritability  or  fatigue  in  the  brain  cells  which  results  finally  in  a 
depression  of  their  activity  sufficient  to  cause  unconsciousness.     It 
is  known  that  functional  activity  in  the  muscle  is  accompanied  by 
the  formation  of  acid  waste  products,  especially  sarcolactic  acid, 
and  that  if  not  removed  as  quickly  as  formed  these  products  cause 
a  diminution  and  finally  a  loss  of  irritability.     The  central  nerve 
tissues  in  activity  show  also  an  acid  reaction.     Moreover,  if  lactic 
acid  or  its  sodium  salt  is  injected  into  the  blood  it  brings  on  a  con- 
dition of  fatigue  and  finally  a  state  of  unconsciousness.     The  theory, 
therefore,  supposes  that  during  the  waking  hours  the  constant 
activity  of  the  muscles  and  nervous  system  results  in  a  gradual 
accumulation  of  these  waste  products,  since  their  oxidation  and 
removal  does  not  keep  pace  with  their  production.     The  end- 
result  is  a  diminishing  irritability  of  the  central  nervous  system, 
especially  perhaps  of  the  cortex,  which  results  finally  in  invol- 
untary sleep,  although  normally  the  accumulation  is  not  carried 
to"  this  extreme,  since  it  is  our  habit  to  induce  sleep,  when  the 
sensations  of  sleepiness  become  apparent,  by  withdrawing  ourselves 
from  excitations,  mental  or  sensory.     No  experimental  confirma- 
tion of  this  theory  has  been  furnished. 

2.  Consumption  of  the  Intramolecular  Oxygen. — Pflugerij:  suggests 
that  the  cause  of  sleep  lies  essentially  in  the  fact  that  the  brain  cells 
during  the  waking  hours  use  up  their  store  of  oxygen  more  rapidly 
than  it  can  be  replaced  by  the  absorption  of  oxygen  from  the  blood. 
The  result  is  a  gradual  reduction  in  irritability;    so  that  when 
external  stimuli  are  withdrawn  the  oxidations  in  the  cells  sink 

*  For  a  very  complete  statement  of  the  theories  of  sleep  and  for  the 
literature  in  general,  see  the  excellent  book  by  Pieron,  "Le  probleme  physio- 
logique  du  sommeil,"  Paris,  1913. 

t  Preyer,  "Centralblatt  f.  d.  med.  Wiss.,"  13,  577,  1875;  and  Obersteiner, 
"Allgemeine  Zeitschrift  f.  Psychiatrie,"  29,  224,  1872-73. 

1  Pfluger,  "Archiv  f.  d.  gesammte  Physiologic,"  10,  468,  1875. 


266  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

below  the  level  necessary  to  arouse  consciousness.  During  sleep 
the  store  of  intramolecular  oxygen — that  is,  the  oxygen  synthet- 
ically combined  by  anabolic  processes  to  form  the  irritable  living 
matter — is  again  replenished.  The  fundamental  conception  on 
which  this  theory  rests,  the  idea,  namely,  of  a  storage  of  intra- 
molecular oxygen,  has  been  practically  abandoned. 

3.  Toxin  Theories. — Quite  a  number  of  writers  have  assumed 
that  some  special  toxin,  which  might  be  called  a  hypnotoxin, 
is  formed  during  the  waking  hours,  and  finally  accumulates  in 
sufficient  quantity  to  inhibit  the  activity  of  the  cortical  cells.     A 
specific  view  of  this  kind  has  been  proposed  by  Pieron,  and  to  a 
certain  extent  has  been  supported  by  experiments.     It  has  been 
shown  that  very  young  dogs,  when  deprived  completely  of  sleep, 
will  die  within  four  to  six  days.     Pieron,  making  use  of  the  method 
of  experimental  insomnia,  states  that  dogs  kept  awake  for  periods 
of  thirty  to  three  hundred  hours  show  evidence  of  an  intoxication, 
not  only  in  the  extreme  somnolence  manifested,  but,  microscopi- 
cally, in  that  the  cortical  cells  in  the  frontal  region  are  distinctly 
altered.    When  the  blood  or  cerebrospinal  liquid  of  such  animals 
is  injected  into  the  brain-ventricles  (fourth  ventricle)  of  another 
animal,  the  latter  is  thrown  into  a  condition  of  somnolence,  and 
exhibits  changes  in  his  cerebral  cortex  similar  to  those  in  the  dog 
suffering  from  insomnia.     This  assumed  hypnotoxin  is  precipitated 
by  alcohol  and  is  destroyed  by  a  temperature  of  65°  C.     In  his 
complete  theory  the  author  supposes  that  the  toxin  acts  directly 
to  arouse  somnolence,  but  that  the  sudden  advent  of  deep  sleep 
is  due  to  the  fact  that  the  toxin  sets  into  action  some  unknown 
nervous  inhibitory  mechanism. 

4.  The  Neuron  Theory. — Duval,*  Cajal,  and  others  have  applied 
the  neuron  doctrine  to  explain  the  occurrence  of  sleep.     According 
to  the  neuron  conception,  the  connection  between  the  cells  in  the 
cortex  and  the  incoming  impulses  along  the  afferent  paths  is  made  by. 
the  contact  of  the  terminal  arborizations  of  the  afferent  fibers  with 
the  dendrites  of  the  cell.     Assuming  that  these  latter  processes  are 
contractile,  Duval  supposes  that  sleep  is  caused  mechanically  by 
their  retraction,  which  results  in  breaking  the  connections  and 
thus  withdrawing  the  brain  cells  from  the  possibility  of  external 
stimulation.     Conductivity  is  re-established  upon  awaking  by  the 
elongation  and  intermingling  of  the  processes  again  re-establishing 
physiological  connections.     The  numerous  efforts  made  to  demon- 
strate the  fact  of  a  retraction  of  the  dendritic  processes  by  histo- 
logical  examinations  of  brains  during  sleep  or  narcosis  have,  how- 
ever, not  been  successful. 

*  Duval,  "Comptes  rendus  de  la  soc.  de  biol,"  February,  1895;  and  Cajal, 
"Archiv  f.  Anat.  (u.  Physiol.),"  375,  1895. 


THE    PHYSIOLOGY    OF    SLEEP.  267 

5.  Inhibitory   Theories. — Some  authors  regard  the   condition 
of  sleep  as  caused  by  a  process  of  inhibition  (Pawlow),  although 
the  mechanism  by  which  this  inhibition  is  exerted  and  the  cause 
of  its  periodic  recurrence  are  not  explained.     Shepard*  defines 
sleep  as  a  dominance  in  attention  of  a  group  of  fatigue  sensa- 
tions which  inhibit  the  motor  processes  and  the  sensations  aroused 
through  the  usual  avenues  of  sense. 

6.  Anemia  Theories  of  Sleep. — It  is  known  that  experimental 
interference  with  the  supply  of  blood  to  the  brain  brings  on  uncon- 
sciousness practically  immediately.     Quite  naturally,  therefore, 
it  has  been  suggested  that  the  alternation  between  sleeping  and 
waking  may  be  connected  with  a  rhythmical  variation  in  the 
blood-flow  through  the  cortex.     Numerous  facts  in  physiology 
have  made  it  probable  that  during  sleep  there  is  a  diminished  flow 
of  blood  through  the  brain,  a  condition  of  cerebral  anemia.     In 
animals  with  the  brain  exposed  or  with  a  glass  window  in  the 
skull  it  has  been  observed  directly  that  the  flow  of  blood  to  the 
cortex    is    diminished  during    sleep.     Mosso's  plethysmographic 
experiments  mentioned  above  have  been  given  a  similar  inter- 
pretation, and  TarchanofTs  observations  upon  sleeping  dogs,  as 
well  as  direct  determinations  upon  man  by  Brush  and  Fayer- 
weather,   show    that    the    arterial    pressure    falls  during  sleep. 
Hooker  f  has  shown  that  the  venous  pressure  also  falls  during 
sleep,  and  that  the  cutaneous  veins  of  the  hand  may  exhibit  a 
pulse,  indicating  a  dilatation  of  the  cutaneous  arteries.     Inas- 
much as  the  lessened  pressure  in  the  arteries  is  accompanied  by  a 
dilatation  of  the  vessels  of  the  skin,  as  shown  by  the  plethysmo- 
graph,  it  is  probable,  when  the  facts  previously  mentioned  are 
taken  into  consideration,  that  the  diminished  pressure  in  the 
arteries  forces  less  blood  through  the  brain  and  more  through  the 
dilated  vessels  of  the  skin.     In  fact,  as  is  explained  in  the  section 
on  circulation,  it  is  probable  that  the  blood-flow  through  the 
brain  is  normally  regulated  indirectly  by  the  circulation  in  other 
parts  of  the  body.     Constriction  of  blood-vessels  elsewhere  in- 
creases arterial   pressure   and   shunts   more   blood  through  the 
brain,  and  vice  versa.    This  general  view  is  in  accord  with  the  fact 
that  sensory  stimuli  and  increased  mental  activity  are  accom- 
panied by  a  constriction  of  the  blood-vessels  (of  the  skin)  and  a 
rise  of  arterial  pressure,  while,  on  the  other  hand,  mental  inac- 
tivity and  especially  sleep  are  accompanied  by  a  dilatation  of  the 
blood-vessels  of  the  body  (skin  vessels)   and  a  fall  of  arterial 
pressure^     Many   facts,   therefore,    point   to   an   anemic   condi- 

*  Shepard,  "The  Circulation  and  Sleep"  ("Univ.  of  Michigan  Studies," 
Scientific  Series,  vol.  i,  1914). 

t  Hooker,  "American  Journal  of  Physiology,"  35,  73,  1914. 


268  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

tion  of  the  brain  during  sleep,  and  some  physiologists  have  be- 
lieved that  this  condition  precedes  and  causes  the  state  of  sleep, 
while  others  take  the  opposite  view  that  it  follows  and  is  merely 
one  result  of  sleep.  On  the  basis  of  the  plethysmographic  ex- 
periments mentioned  above  the  author*  has  proposed  a  theory 
of  sleep  in  which  the  diminished  flow  of  blood  to  the  brain  is  ex- 
plained and  is  assumed  to  be  the  chief  factor  in  bringing  on  sleep. 
The  theory  assumes  that  the  periodicity  of  sleep  is  dependent 
mainly  upon  a  rhythmical  loss  of  tone  in  the  vasomotor  center  in 
the  medulla  in  consequence  of  fatigue  from  continued  activity 
during  the  waking  hours.  That  is,  the  vasomotor  center  is  in 
constant  action  during  this  period;  the  continued  flow  of  sensory 
stimuli  and  the  constant  activity  of  the  brain  act  reflexly  on  this 
center  and  through  it  cause  a  constriction  of  the  blood-vessels  of 
the  body,  particularly  of  the  skin,  by  means  of  which  the  blood- 
flow  through  the  brain  is  maintained  with  an  adequate  velocity. 
In  consequence  of  this  varying  but  constant  activity  the  center 
undergoes  fatigue;  stronger  and  stronger  stimulation  is  necessary 
to  maintain  its  normal  tone,  and  eventually  its  effect  on  the  blood- 
pressure  becomes  insufficient  to  maintain  an  adequate  flow  through 
the  brain  and  unconsciousness  or  sleep  results,  even  against  one's 
desires,  as  is  shown  by  the  experience  of  those  who  have  attempted 
to  keep  awake  much  beyond  the  habitual  period.  Ordinarily, 
however,  this  fatigue  of  the  vasomotor  center  and  its  resulting 
tendency  to  a  cessation  of  activity  is  favored  by  our  voluntary 
withdrawal  of  stimulation.  Our  preparations  for  sleep,  closure  of 
eyes,  darkened  and  if  possible  quiet  room,  cessation  from  disturbing 
thoughts,  result  in  a  diminution  of  the  sensory  and  mental  stimuli 
that  normally  play  upon  the  vasomotor  center.  The  cessation 
of  such  stimuli  may,  indeed,  at  any  time  be  all  that  is  necessary 
to  bring  about  a  partial  loss  of  activity  in  this  center,  a  les- 
sened flow  of  blood  through  the  brain,  and  a  period  of  sleep  which, 
however,  is  usually  short.  If,  however,  the  vasomotor  center  has 
been  previously  fatigued,  as  may  be  supposed  to  be  the  case  at  the 
end  of  the  day,  the  withdrawal  of  these  stimuli  permits  it  to  fall 
into  a  more  complete  state  of  inactivity,  and  the  diminution  of 
blood-flow  to  the  brain  and  the  state  of  unconsciousness  is  longer 
lasting, — lasts  indeed,  according  to  the  curves  of  which  an  example 
is  given  in  Fig.  116,  until  the  gradual  resumption  of  activity  in  the 
vasomotor  center  brings  about  a  constriction  of  the  blood-vessels 
of  the  body  and  thus  drives  enough  blood  through  the  brain  to 
cause  spontaneous  awakening.  A  third  factor  which  must  aid  in 
the  production  of  unconsciousness  as  a  result  of  the  lessened  flow 
of  blood,  and  in  the  return  of  consciousness  in  connection  with 
*  Howell,  "Journal  of  Experimental  Medicine,"  2,  313,  1897. 


THE    PHYSIOLOGY    OF    SLEEP.  269 

the  increased  flow  of  blood,  is  the  greater  or  less  fatigue  of  the 
cortical  cells  themselves  after  a  day's  activity,  and  their  greater 
irritability  after  a  night's  rest.  Many  factors,  therefore,  co-oper- 
ate in  the  development  of  the  normal  state  of  sleep  lasting  for 
six  to  eight  hours  out  of  twenty-four,  but  the  central  factor  which 
explains  its  rapid  onset,  involving  nearly  simultaneously  all  the 
conscious  areas  of  the  brain,  whether  previously  fatigued  or  not, 
and  the  equally  sudden  restoration  to  consciousness  of  the  entire 
cortex,  is  to  be  found  in  the  amount  of  blood-flow  to  the  brain. 
Under  normal  conditions  this  is  the  factor  that  stands  in  most 
immediate  relation  to  that  appearance  and  disappearance  of  full 
consciousness  which  mark  for  us  the  limits  of  sleep.  A  similar 
view  is  advocated  by  Hill,*  who  believes,  however,  that  the  regu^ 
lation  of  the  blood-flow  through  the  brain  is  effected  through  the 
vasomotor  control  of  the  splanchnic  area,  whereas  the  author's 
view  is  that  the  regulation  is  effected  mainly  through  variations 
in  the  cutaneous  circulation, — that. is,  for  the  normal  occurrence 
of  sleep.  The  drowsiness  that  follows  a  heavy  meal  is  probably  due 
mainly  to  the  mechanical  effect  of  a  dilatation  of  the  blood-vessels  of 
the  viscera  and  the  consequent  diminution  in  the  blood-flow 
through  the  brain;  but  the  sleep  that  occurs  at  the  end  of  the  day 
is  associated  with  a  dilatation  of  the  blood-vessels  of  the  skin  of 
the  trunk  and  extremities.  What  the  condition  in  the  visceral 
organs  may  be  at  such  times  we  have  at  present  no  means  of 
knowing.  It  should  be  stated  that  in  opposition  to  these  veins 
regarding  an  anemic  condition  of  the  brain  during  sleep,  Shepard  f 
reports,  as  the  result  of  an  extensive  'series  of  plethysmographic 
observations  made  upon  two  individuals  with  defects  in  the  skull, 
that  during  sleep  the  volume  of  the  brain  is  increased.  He 
believes,  therefore,  that  during  this  period  there  is  a  vascular 
dilatation  in  the  brain  and  an  increased  circulation,  that  the  brain, 
in  fact,  receives  its  greatest  supply  of  blood  during  its  period  of 
least  activity.  This  conclusion  is  at  variance  with  what  we 
should  expect  from  observations  on  the  blood-flow  in  other  organs 
during  their  periods  of  maximum  and  minimum  functional  activity. 
The  author  concludes  also  from  his  observations  that  the  brain 
must  possess  an  efficient  supply  of  vasomotor  nerves,  which  during 
the  waking  hours  are  in  tonic  activity,  but  in  sleep  suffer  a  dim- 
inution in  tone  that  leads  to  a  local  dilatation.  Evidence  from 
other  sources  (p.  636),  on  the  contrary,  makes  it  rather  improbable 
that  the  brain  possesses  an  efficient  vasomotor  system. 

Hypnotic  Sleep. — The  sleep  that  can  be  produced  by  so-called 

*Hill,  The   "Physiology  and  Pathology  of  the  Cerebral  Circulation," 
London,  1896. 

t  Shepard,  loc.  cit. 


270  PHYSIOLOGY    OF    CENTRAL    NERVOUS    SYSTEM. 

suggestion,  the  sleep  of  hypnotism,  has  been  studied  by  means 
of  the  plethysmographic  method.*  The  result,  so  far  as  the 
volume  of  the  arm  and  hand  is  concerned,  shows  that  in  this  con- 
dition, unlike  normal  sleep,  there  is  a  marked  diminution  in 
volume,  and,  therefore,  we  may  believe,  an  increased  constriction 
of  the  blood-vessels  of  the  skin.  This  observation  accords  with 
the  blanched  appearance  of  the  skin  of  the  extremities,  and  with 
the  statement  that  in  deep  hypnotic  sleep  the  skin  does  not  bleed 
readily  when  pricked  with  a  needle.  In  view  of  our  limited  knowl- 
edge, however,  it  would  be  hazardous  to  base  any  comparison 
between  normal  and  hypnotic  sleep  upon  this  single  fact.  Some 
authors,!  in  fact,  doubt  whether  there  is  a  true  hypnotic  sleep. 
They  incline  to  the  view  that  the  immobilization  or  diminished 
excitability  produced  by  hypnotic  suggestion  or  manipulation 
simply  passes  into  a  condition  of  natural  sleep. 

*  Walden,  "American  Journal  of  Physiology,"  4,  124,  1900-01. 
t  Pi6ron,  loc.  tit. 


SECTION  III. 
THE  SPECIAL  SENSES. 


CHAPTER  XIV. 

CLASSIFICATION  OF  THE  SENSES  AND  GENERAL 
STATEMENTS. 

Under  the  general  term  sense  organ  we  may  include  not  only 
the  peripheral  organ  on  which  the  stimulus  acts,  but  also  the  sensory 
path  through  which  the  impulses  are  conveyed  to  the  central 
nervous  system  and  the  cortical  center  by  means  of  which  the 
reaction  in  consciousness  is  mediated. 

Classification  of  the  Senses. — In  general,  we  attempt  to 
distinguish  the  various  sense  organs  by  the  differences  in  their 
end  reaction  in  consciousness.  Each  sense  organ  gives  a  different 
kind  of  response,  the  nature  and  distinctive  features  of  which 
are  recognized  subjectively.  The  conscious  sensations  are  said 
to  differ  in  quality  or  modality.  The  qualitative  difference  in 
some  cases  is  very  distinct, —the  difference  between  sensations  of 
sound  and  of  vision,  for  instance, — and  on  this  subjective  difference 
we  base  our  efforts  to  give  specific  names  to  the  sense  organs  con- 
cerned. This  means  of  classification  is  not,  however,  applicable 
in  all  cases.  While  many  of  our  sensations  are  so  distinct  in  quality 
that  we  can  recognize  them  and  name  them  without  difficulty, 
others  are  of  a  more  obscure  character.  In  addition  to  our  sensa- 
tions of  vision,  hearing,  smell,  taste,  pressure,  temperature,  and 
pain,  there  are  doubtless  many  other  sensations  whose  conscious 
reaction  is  less  distinct  in  quality  and  for  which  our  subjective 
means  of  recognition  and  classification  are  less  satisfactory  or 
entirely  inadequate.  Such,  for  instance,  are  the  sensations  from 
the  muscles,  from  the  semicircular  canals  and  the  vestibular  sacs 
of  the  ear,  and  from  many  of  the  visceral  organs.  For  the  recogni- 
tion and  classification  of  these  senses  and  sense  organs  it  is  neces- 
sary to  fall  back  upon  the  methods  of  anatomical  and  physiological 
analysis,  methods  which  in  many  respects  are  uncertain.  So  also 
within  the  limits  of  any  sensation  of  a  given  quality  or  modality, 
we  distinguish  certain  subqualities.  In  vision  we  have  many  dif- 

271 


272  THE    SPECIAL    SENSES. 

ferent  qualities  which  we  designate  by  special  names, — the  series 
of  different  colors,  for  example.  In  sound  sensations  we  distinguish 
different  tones  and  different  qualities  of  tones.  But  here,  again, 
the  subjective  mark  is  often  so  indistinct  in  consciousness 
that  it  cannot  be  used  satisfactorily  for  purposes  of  classifica- 
tion. In  the  odor  sensations  we  distinguish  many  different  quali- 
ties, each  recognizable  at  the  time  that  it  is  experienced,  but  their 
characteristics  are  so  fugitive  that  so  far  it  has  not  been  possible 
to  name  them  or  group  them  in  any  satisfactory  way.  In  studying 
the  qualities  of  the  various  sensations,  so  far  as  they  are  recogniz- 
able, the  effort  of  physiology  has  been  to  connect  them  with  some 
definite  anatomical  or  physiological  peculiarity  in  the  sense  organs 
concerned.  The  final  explanation  of  the  differences  in  quality 
involves  a  study  of  the  nature  and  properties  of  consciousness 
itself, — a  subject  which  as  yet  has  not  been  undertaken  by  physi- 
ology. At  present  we  accept  the  fact  of  consciousness  and  the 
fact  that  there  are  different  kinds  or  qualities  of  consciousness, 
and  our  investigations  are  directed  only  toward  ascertaining 
the  anatomical,  physical,  and  chemical  properties  of  the  organs 
involved  in  the  production  of  these  subjective  changes. 

In  former  times  it  was  customary  to  divide  the  sensations  into 
two  different  groups, — the  special  and  the  common  senses, — the 
former  including  the  so-called  five  senses  of  man, — namely,  sight, 
hearing,  touch,  taste,  and  smell, — while  under  the  latter  were 
grouped  all  other  sensations  of  less  distinctive  qualities.  In  physi- 
ology the  belief  that  man  has  only  five  special  senses  has,  however, 
long  been  abandoned.  The  sense  of  touch  as  ordinarily  understood 
has  been  shown  to  consist  of  three  or  more  distinct  senses,  namely, 
pressure  (in  its  several  varieties),  heat  and  cold;  and  the  sense 
of  pain  exhibited  by  the  skin  is  in  all  essential  respects  as  special 
and  characteristic  as  those  just  named.  There  is,  however,  no 
certain  standard  as  to  what  shall  constitute  a  special  in  con- 
tradistinction to  a  common  sense;  so  that  a  classification  based 
on  this  nomenclature  is  unsatisfactory.  In  one  respect,  how- 
ever, our  senses  show  a  difference  which  may  be  used  as  a  basis 
for  dividing  them  into  two  general  groups.  This  difference 
lies  in  the  manner  of  projection.  We  may  assume  that  all  of 
our  sensations  are  aroused  directly  in  the  brain.  In  that  organ 
take  place  the  final  changes  which  react  in  consciousness.  But 
in  no  case  are  we  conscious  that  this  is  the  case.  On  the 
contrary,  we  project  our  sensations  either  to  the  exterior  of 
the  body  or  to  some  peripheral  organ  in  the  body,  the  effort 
being  apparently  to  project  them  to  the  place  where  experi- 
ence has  taught  us  that  the  acting  stimulus  arises.  We  may 
divide  the  senses,  therefore,  into  two  great  groups:  (1)  The 


CLASSIFICATION    OF   THE    SENSES.  273 

external  or  rather  the  exterior  senses,  or  those  in  which  the  sensa- 
tions are  projected  to  the  exterior  of  the  body,  and  which  form/ 
therefore,  the  means  through  which  we  become  acquainted  with  the 
outside  world.  The  exterior  senses  include  sight,  hearing,  taste, 
smell,  pressure,  and  temperature  (heat  and  cold).  (2)  The  internal 
or  interior  senses,  or  those  in  which  the  sensations  are  projected  to 
the  interior  of  the  body.  It  is  through  these  senses  that  we  acquire 
a  knowledge  of  the  condition  of  our  body  and  perhaps  also  a  knowl- 
edge of  ourselves  as  an  existence  or  organism  distinct  from  the  ex- 
ternal world.  Among  the  interior  senses  we  must  include  pain, 
muscle  sense,  the  sensations  from  the  semicircular  canals  and  ves- 
tibule of  the  internal  ear,  hunger,  thirst,  sexual  sense,  fatigue,  and 
in  addition  perhaps  other  less  definite  sensations  from  the  visceral 
organs.  This  line  of  demarcation,  although  it  holds  so  well  in 
most  cases,  is  not  absolutely  distinctive.  The  temperature  sense, 
for  instance,  is,  so  to  speak,  on  the  border  line  between  the  two 
groups;  we  may  project  this  sensation  either  to  the  exterior  or 
to  the  interior  according  to  circumstances.  When  the  temperature 
nerves  are  excited  simultaneously  with  the  pressure  nerves,  we 
project  the  sensation  to  the  exterior,  to  the  stimulating  body.  If 
the  skin  is  touched  by  a  hot  or  cold  solid  object  we  speak  of  the 
object  as  being  hot  or  cold.  If,  however,  the  same  nerves  are 
stimulated  by  warm  gases  or  even  liquids  under  conditions  that 
do  not  involve  the  pressure  sense  we  refer  the  change  to  ourselves, — 
we  are  hot  or  cold,  as  the  case  may  be.  So  also  when  the  skin  is 
heated  by  the  blood  the  resulting  sensation  is  projected  to  the 
skin.  It  would  seem  that  the  habit  of  projection  is  acquired  by 
experience,  and  that  those  senses  whose  organs  are  habitually 
affected  by  objects  from  without  we  learn  to  project  to  the  object 
giving  rise  to  the  stimulus. 

The  Doctrine  of  Specific  Nerve  Energies. — The  term  specific 
nerve  energy  we  owe  to  Johannes  Miiller  (1801-1858).  The  term 
is  in  some  respects  unfortunate,  as  at  present  in  the  physical  sci- 
ences the  word  energy  is  used  to  designate  certain  specific  properties 
of  matter.  The  phrase  specific  nerve  energy  in  physiology,  however, 
is  intended  to  designate  the  fact  that  each  sensory  unit  arouses  or 
mediates  its  own  specific  quality  of  sensation,  the  specific  energy  of 
the  optic  apparatus  being  visual  sensations,  of  the  auditory  apparatus 
sound  sensations,  etc.,  and  each  sensory  nerve  or  apparatus  can 
give  no  other  than  its  own  quality  of  sensation.  Whether  this 
specificity  in  the  reaction  of  each  sensory  nerve  is  due  to  some  pecu- 
liarity in  the  nerve  itself  or  its  peripheral  end-organ,  or  to  a  pecu- 
liarity of  the  part  of  the  brain  in  which  it  terminates  Miiller  left 
an  open  question,  although  he  called  attention  to  the  fact  that 
the  central  ending  is  capable  of  giving  its  specific  effect  in  con- 
18 


274  THE  SPECIAL  SENSES. 

sciousness  independently  of  the  conducting  nerve  fibers.  With 
regard  to  this  latter  question  the  opinions  of  physiologists  still 
differ.  Most  physiologists,  perhaps,  adopt  the  view  that  the 
specific  reaction  in  consciousness  is  due  to  the  central  ending,— 
that,  in  other  words,  the  different  sensory  parts  of  the  cortex 
give  different  kinds  or  qualities  of  consciousness,  while  the  sensory 
nerve  fibers  are  simply  conductors  of  nerve  impulses,  which, 
however  much  they  may  differ  in  intensity,  are  qualitatively 
the  same  in  all  nerve  fibers.  According  to  this  view,  it  would 
result,  as  du  Bois-Reymond  expressed  it,  that,  if  the  auditory 
nerve  fibers  were  attached  to  the  visual  center  and  the  optic 
fibers  to  the  auditory  center,  we  would  see  the  thunder  and  hear 
the  lightning.  Each  typical  sense-organ  from  this  standpoint 
consists  of  three  essential  parts:  the  central  ending,  which  deter- 
mines the  quality  of  the  sensation;  the  peripheral  end-organ, 
retina,  cochlea,  etc.,  which  determines  whether  or  not  any  given 
form  of  stimulus  shall  be  effective  and  which  in  most  cases  is  con- 
structed so  as  to  be  responsive  to  a  special  form  of  stimulus  desig- 
nated as  its  adequate  stimulus;  and  of  connecting  neurons  whose 
only  function  is  to  conduct  the  nerve  impulses  originating  in  the 
end-organ.  The  fact,  therefore,  that  the  light  waves  can  stimulate 
the  rods  and  cones  of  the  retina,  but  are  an  inadequate  stimulus 
probably  to  the  hair  cells  of  the  cochlea  or  the  taste  buds  of  the 
tongue,  is  due  to  a  peculiarity  in  structure  of  the  rods  and  cones; 
but  the  fact  that  the  impulses  conducted  by  the  optic  fibers  arouse 
a  peculiar  modality  of  sensation  is  not  due  to  any  peculiarity  in 
structure  in  these  fibers  or  in  the  rods  and  cones,  but  to  a  charac- 
teristic structure  of  the  optic  centers.  The  positive  experimental 
evidence  for  the  correctness  of  this  view  is  not  conclusive,  but,  on 
the  whole,  is  impressive.  Such  facts  as  the  following  may  be  noted : 

1.  When  sensory  nerve  fibers  are  stimulated  otherwise  than 
through  their  end-organs  each  reacts,  if  it  reacts  at  all,  according 
to  its  specific  energy, — that  is,  it  produces  its  own  quality  of  sensa- 
tion.   When  the  optic  nerve  is  cut,  for  instance,  the  mechanical 
stimulus  causes  a  flash  of  light ;  when  the  chorda  tympani  is  stimu- 
lated in  the  tympanic  cavity  by  mechanical,  electrical,  or  chemical 
stimuli  sensations  of  taste  are  aroused. 

2.  Mechanical  pressure  upon  the  peripheral  nerves  distributed  to 
the  skin  may  cause  a  loss  of  some  of  the  cutaneous  senses  in  certain 
areas  of  the  skin  with  a  retention  of  others.    Thus  the  senses  of 
pressure  and  temperature  may  be  lost  and  that  of  pain  retained, 
or  pain  may  be  lost  and  pressure  retained.     A  similar  dissocia- 
tion of  the  sensations  of  the  skin  in  definite  regions  maybe 
observed  after  localized  lesions  of  the  spinal  cord,  or  during  the 
process  of  regeneration  that  follows  suture  of  a  severed  nerve. 
Such  facts  agree  with  the  view  that  each  sense  has  its  own  set 


CLASSIFICATION    OF    THE    SENSES.  275 

of  nerve-fibers;  those  that  mediate  pain  cannot  by  a  mere  modi- 
fication of  the  stimulus  give  also  a  sense  of  pressure. 

3.  The  only  objective  manifestation  of  a  nerve  impulse  that 
we  can  study  in  the  nerve  itself  is  the  electrical  change  that 
accompanies  it  or  perhaps  constitutes  its  essence.  This  electrical 
change  is  qualitatively  the  same  in  all  kinds  of  nerve  fibers,  and  this 
fact  agrees  with  the  view  that  the  nerve  impulse  is  qualitatively  the 
same  in  all  fibers. 

So  far  as  the  sensory  nerve  fibers  are  concerned,  the  chief  ob- 
jection to  this  view  of  the  doctrine  of  specific  nerve  energies  is 
found  perhaps  in  the  difficulty  or  impossibility  of  applying  it  to 
the  explanation  of  color  vision.  According  to  the  strict  interpreta- 
tion of  the  view,  each  fundamental  color  sense,  being  distinct  in 
quality,  should  be  mediated  by  its  own  set  of  nerve  fibers.  When 
Helmholtz  first  formulated  his  theory  of  color  vision  he  spoke, 
therefore,  of  three  kinds  of  nerve  fibers, — the  red,  the  green,  and 
the  violet, — each  when  stimulated  alone  giving  its  own  specific 
sensation  and  not  capable  of  giving  any  other.  The  facts  accumu- 
lated regarding  color  vision,  however,  seem  to  show  that  this  view 
will  not  hold.  One  and  the  same  cone,  with  its  connecting  fiber, 
may  give  rise  to  any  or  all  of  the  primary  color  sensations,  and, 
unless  we  choose  to  further  subdivide  the  nerve  unit  and  assume 
that  the  separate  nerve  fibrils  of  which  the  axis  cylinder  is  composed 
constitute  the  separate  conductors  for  the  primary  sense  qualities, 
it  would  seem  to  be  impossible  to  apply  the  doctrine  of  specific 
energies  to  this  case.  Not  too  much  weight  should  be  given  per- 
haps to  this  objection.  For  it  must  be  remembered  that  all  of  our 
present  theories  of  color  vision  are  unsatisfactory,  and  possibly 
when  we  attain  to  the  right  point  of  view  the  facts  may  not  be 
so  difficult  to  interpret  in  terms  of  this  theory  of  specific  energies. 

The  alternative  view  proposed  in  place  of  the  doctrine  of 
specific  nerve  energies  assumes  that  the  nerve  impulses  may 
vary  in  quality  as  well  as  in  intensity,  and  that  therefore  one  and 
the  same  nerve  fiber  may  arouse  different  qualities  of  sensation  and 
have  different  end  effects  according  to  the  character  of  the  impulse 
conveyed.  This  point  of  view  is  not  capable  of  much  discussion, 
since  there  are  no  positive  facts  that  support  it.  It  is  logically 
satisfactory  in  meeting  the  cases  in  which  the  former  view  seems 
to  be  unsatisfactory.  It  is  difficult,  however,  in  our  ignorance  of 
the  nature  of  the  nerve  impulse  to  imagine  in  what  respects  it  may 
possibly  differ  in  character. 

The  Weber-Fechner  (Psychophysical)  Law. — One  difficulty 
that  has  been  encountered  in  the  physiological  study  of  sensory 
nerves  is  that  the  end  reaction  cannot  be  measured  with  exactness. 
With  efferent  nerves  the  end  reaction  is  a  contraction  or  secretion 


276 


THE    SPECIAL    SENSES. 


that  can  be  estimated  quantitatively  in  terms  of  our  physical  and 
chemical  units  of  measurement.  But  the  end  reaction  of  a  sensory 
nerve  is  a  state  of  consciousness  for  which  we  have  no  standard  of 
measurement.  Weber,  in  studying  the  relation  between  the 
strength  of  the  stimulus  and  the  amount  of  the  resulting  sensation, 
availed  himself  of  the  method  of  the  least  detectible  change  in  sen- 
sation; that  is,  he  determined  the  increase  in  stimulus  at  different 
levels  necessary  to  cause  a  just  perceptible  increase  in  the  sensation. 
By  means  of  this  method  he  arrived  at  the  significant  result  that 
the  increase  in  stimulus  necessary  to  cause  this  change  is,  within 
physiological  limits,  a  definite  fractional  increment  of  the  acting 
stimulus.  If,  for  instance,  with  a  weight  of  30  gms.  upon 
the  finger  it  requires  an  increment  of  •£$ — that  is,  one  additional 
gram — to  make  a  just  perceptible  difference  in  the  pressure  sensa- 


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EXCITATION  X. 

Fig.  118. — Curve  to  indicate  the  Weber-Fechner  law  of  a  logarithmical  relation  be- 
tween excitation  and  sensation. — (From  Waller.)  The  excitations  are  indicated  along  the 
abscissas,  the  sensations  along  the  ordinates.  The  increase  in  sensation  is  represented  as  tak- 
ing place  in  equal  steps,  "the  minimal  perceptible  difference,"  while  the  corresponding 
excitations  require  an  increasing  increment  of  i  at  each  step,  namely  1,  1.33,  1.77,  2.37, 
etc.  That  is,  for  equal  increments  of  sensation  increasing  increments  of  stimulation  are 
necessary. 

tion,  then,  with  a  weight  of  60  gms.  upon  the  finger  the  addition 
of  another  gram  would  not  be  perceived ;  it  would  require  again  an 
increment  of  -^ — that  is,  2  gms. — to  make  a  just  perceptible  dif- 
ference in  sensation.  This  relationship  is  known  as  Weber's  law. 
While  its  exactness  has  often  been  disputed,  it  seems  to  be  generally 
admitted  that  for  a  median  range  of  stimulation  the  law  expresses 
the  approximate  relation  between  the  two  variables  considered. 
Fechner  attempted  to  give  this  law  a  more  quantitative  and  ex- 
tensive application  by  assuming  that  just  perceptible  differences 


CLASSIFICATION    OF    THE    SENSES.  277 

in  sensation  represent  actually  equal  amounts  of  sensation.  Ac- 
cepting this  assumption,  we  can  express  the  relationship  between 
stimulus  and  sensation  as  determined  by  Weber's  experiments  by 
saying  that  for  the  sensation  to  increase  by  equal  amounts, — that  is, 
by  arithmetical  progression, — the  stimulus  must  vary  according 
to  a  certain  factor, — that  is,  by  geometrical  progression.  The 
sensation  may  be  regarded  as  a  geometrical  function  of  the 
stimulus.  If  the  relation  between  stimulus  and  sensation  is  repre- 
sented as  a  curve  in  which  the  ordinates  express  the  sensation  in- 
creasing by  equal  amounts,  and  the  abscissas  the  corresponding 
stimuli  increasing  at  each  interval  by  J,  a  result  is  obtained  such  as 
is  represented  in  the  accompanying  figure  (Fig.  118).  A  curve  of 
this  kind  is  a  logarithmical  cu,rve,  and  Fechner  expressed  the  rela- 
tionship between  stimulus  and  sensation  in  what  has  been  called  the 
psychophysical  law, — namely,  that  the  sensation  varies  as  the 
logarithm  of  the  stimulus. 


CHAPTER   XV. 
CUTANEOUS  AND  INTERNAL  SENSATIONS. 

General  Classification. — According  to  the  older  views,  the 
sensory  nerves  of  the  skin  give  sensations  of  touch.  Modern 
physiology  has  shown,  however,  that  these  nerves  mediate  at 
least  four  different  qualities  of  sensation — namely,  pressure, 
warmth,  cold,  and  pain.  Our  so-called  touch  sensations  are 
usually  compound,  consisting  of  a  pressure  and  a  temperature 
component  and  also  very  frequently  an  element  of  muscle  sense 
when  muscular  efforts  are  involved,  as,  for  instance,  in  measuring 
weights  or  resistances.  The  four  sensory  qualities  enumerated 
constitute  the  cutaneous  senses,  and  they  are  present,  or,  to 
speak  more  accurately,  the  nerves  through  which  these  senses 
are  mediated  are  present  not  only  over  the  general  cutaneous 
surface  but  also  in  those  membranes — such  as  the  mucous 
membrane  of  the  mouth  and  the  rectum  (stomodeum  and 
proctodeum) — which  embryologically  are  formed  from  the 
epiblast.  The  surfaces  in  the  interior  of  the  body,  on  the 
contrary — such  as  the  membranes  of  the  alimentary  canal, 
muscles,  fasciae,  etc. — have  only  nerves  of  'pain,  but  no  sense 
of  touch  or  temperature.  Of  these  cutaneous  senses,  three — 
pressure,  warmth,  and  cold — may  be  grouped  with  the  exterior 
senses,  the  sensations  being  projected  to  the  exterior  of  the 
body,  into  the  substance  causing  the  stimulation;  although,  as 
was  mentioned  above,  the  temperature  sensations  under  con- 
ditions— fever,  vascular  dilatation,  etc. — may  be  projected  to 
parts  of  the  skin  itself  and  be  felt  as  changes  in  ourselves.  The 
temperature  sensations  are,  in  fact,  projected  to  the  exterior- 
whenever  they  are  combined  with  pressure  sensations,  the  latter 
serving,  as  it  were,  as  the  dominant  sense.  The  pain  sense,  on 
the  other  hand,  belongs  to  the  group  of  interior  senses,  the 
sensations  being  always  projected  into  our  own  body  and  being 
felt  as  changes  in  ourselves. 

Protopathic,  Epicritic,  and  Deep  Sensibility. — In  the  matter  of 
the  classification  of  the  cutaneous  senses  and,  indeed,  the  body  senses 
in  general,  a  new  point  of  view  has  been  suggested  by  Head  and 
Rivers.*     These  authors  made  a  careful  study  of  the  loss  of  sensa- 
tions after  division  of  the  cutaneous  nerves,  and  of  the  subsequent 
gradual  and  separate  return  of  these  sensations  following  upon  suture 
of  the  divided  ends.    They  find  that  in  skin  areas  made  completely 
*  Head  and  Rivers,  "  Brain,"  1905,  99,  and  1908,  323. 
278 


CUTANEOUS    AND    INTERNAL    SENSATIONS.  279 

anesthetic  there  is  present  a  deep  or  subcutaneous  sensibility  to 
pressure  and  movements,  a  sensibility  which  must  be  mediated 
through  sensory  fibers  contained  in  the  nerves  to  the  muscles  In 
the  skin  itself  there  are  present  two  systems  of  sensory  fibers  which 
regenerate  at  different  times  in  a  nerve  that  has  been  severed, 
and  may  be  studied  separately  by  this  means.  One  system 
conveys  sensations  of  pain  and  of  extreme  changes  in  tempera- 
ture, but  the  sensations  are  imperfectly  localized  and  the  sensi- 
bility is  low,  or,  to  express  the  same  idea  in  another  way,  the 
threshold  is  high.  This  kind  of  sensation  is  found  in  the  viscera 
also,  and  it  may  be  considered  from  the  functional  standpoint 
as  a  defensive  agency  toward  pathological  changes  in  the  tissues; 
it  is  designated  as  protopathic  sensibility.  It  is  stated  that  the 
glans  penis  possesses  only  this  kind  of  sensibility.  Protopathic 
sensibility  comprises  three  qualities  of  sensation  and  presum- 
ably three  sets  of  nerve-fibers,  namely — for  pain,  for  heat  (not 
stimulated  below  37°  C.),  and  for  cold  (not  stimulated  above 
26°  C.).  The  second  system  of  fibers  responds  to  stimulations 
by  light  pressures  and  small  differences  in  temperature  between 
26°  and  37°  C.,  the  range  of  temperature  to  which  the  tem- 
perature nerves  of  the  protopathic  system  are  insensitive.  These 
fibers  regenerate  after  lesions  much  more  slowly  than  the  pro- 
topathic variety,  and  since  the  sensations  mediated  by  them 
are  localized  very  exactly,  they  furnish  us  the  means  for  making 
fine  discriminations  of  touch  and  temperature.  For  this  reason 
they  are  described  as  an  epicritic  system,  and  the  corresponding 
sensations  are  designated  as  epicritic  sensibility.  This  system 
of  fibers  is  not  found  in  the  other  organs,  and  it  constitutes, 
therefore,  the  special  characteristic  of  the  skin  area.  In  this 
system  there  are  included  separate  fibers  for  heat,  for  cold,  for 
light  pressures,  and  for  tactile  discrimination.  It  is  through 
the  sensations  mediated  by  these  fibers  that  we  recognize  the 
shape  and  size  of  objects.  According  to  this  classification  we  may 
assume  that  the  posterior  roots  of  the  spinal  nerves  carry  into  the 
spinal  cord  the  following  varieties  of  afferent  fibers : 

Heat  (small  differences). 


Epicritic 


Cutaneous  sensory  fibers  <j 


Protopathic 


Cold  (small  differences). 
Touch  (light  pressures). 
Tactile  discrimination. 
Heat  (extremes). 
Cold  (extremes). 


Pain. 

1  Pressure. 
Pain. 
Muscular  (position). 


The  paths  taken  by  these  fibers  after  entering  the  cord  are  de- 
scribed on  p.  174. 


280 


THE  SPECIAL    SENSES. 


The  distinction  made  by  these  authors  between  the  cutaneous 
and  deep  sensations,  especially  between  the  cutaneous  and  deep 
sensations  of  pressure,  is  very  important  and  must  be  borne  in  mind 
in  all  studies  of  supposed  anesthetic  areas  of  skin.  Whether  the 
distinction  made  by  them  between  protopathic  and  epicritic  sensi- 
bility will  be  established  by  further  observations  is  at  present  an 
open  question.  Two  other  sets  of  observers*  have  used  their 
method  of  study,  namely,  the  section  and  regeneration  of  a  cu- 
taneous nerve  in  man;  but,  unfortunately,  they  do  not  corroborate 


Fig.  119.— Representation  of  the  distribution  of  cold  and  warm  spots  on  the  volar 
surface  of  forearm  in  a  space  2  cms.  by  4  cms.  The  red  dots  represent  the  cold  spots  as 
tested  at  a  temperature  of  10°  C.  The  black  dots  represent  the  warm  spots  as  tested  at  a 
temperature  of  41°  to  48°  C. 

the  findings  of  Head  and  Rivers  in  regard  to  the  different  qualities  of 
sensation  designated  under  the  terms  "epicri tic"  and  "protopathic." 
The  Punctiform  Distribution  of  the  Cutaneous  Senses. — A 
most  interesting  fact  in  regard  to  the  cutaneous  senses  is  that 
they  are  not  distributed  uniformly  over  the  whole  skin,  but  are 
present  in  discrete  points  or  spots.  This  fact  was  first  clearly 
established  by  Blix,f  although  it  was  discovered  independently 
by  Goldscheider  and  in  this  country  by  Donaldson.  These  ob- 
servers paid  attention  chiefly  to  the  warm  and  cold  spots.  The 


CUTANEOUS   AND    INTERNAL   SENSATIONS.  281 

existence  of  these  spots  may  be  demonstrated  easily  by  anyone 
upon  himself  by  moving  a  metallic  point  gently  over  the  skin. 
If  the  point  has  a  temperature  below  that  of  the  skin  it  will  be 
noticed  that  at  certain  spots  it  arouses  simply  a  feeling  of  contact 
or  pressure,  while  at  other  spots  it  gives  a  distinct  sensation  of 
coldness.  If,  on  the  other  hand,  the  point  is  warmer  than  the 
skin  it  will  at  certain  spots  give  a  sensation  of  warmth.  On  mark- 
ing the  cold  and  warm  spots  thus  obtained  it  is  found  that  they 
occupy  different  positions  on  the  skin.  Elaborate  charts  have 
been  made  of  the  warm  and  cold  spots  on  different  regions 
of  the  skin,  the  apparatus  usually  employed  being  a  metal 
tube  through  which  water  of  any  desired  temperature  may  be 
circulated.  The  temperature  of  the  skin,  whatever  it  may  be, 
forms  the  zero  line;  any  object  of  a  higher  temperature  stimulates 
only  the  warm  spots,  while  one  of  a  lower  temperature  acts  upon 
the  cold  spots.  The  pressure  or  tactile  sense  and  the  pain  sense 
are  also  distributed  in  a  punctiform  manner;  they  have  been 
studied  most  carefully  by  von  Frey.*  To  determine  the  loca- 
tion of  the  pressure  points  he  used  fine  hairs  of  different  diam- 
eters fastened  to  a  wooden  handle.  The  cross-areas  of  these 
hairs  are  determined  by  measurements  under  the  micro- 
scope, and  the  pressure  exerted  by  each  is  measured 
by  pressing  it  upon  the  scale  pan  of  a  balance.  The  quotient 
of  the  pressure  exerted  divided  by  the  cross-area  of  the  hair 
in  square  millimeters,  |^2,  reduces  the  pressure  to  a  uniform 
unit  of  area.  For  the  pain  points  fine  needles  may  be  employed 
or  stiff  hairs  similar  to  those  used  for  the  pressure  points.  From 
the  experiments  made  there  seems  to  be  no  doubt  that  each  of 
the  four  cutaneous  senses  has  its  own  spots  of  distribution  in  the 
skin,  those  for  pain  being  most  numerous  and  those  for  warmth 
the  least  numerous.  There  is  some  reason  for  believing  also  that 
the  nerve  endings  mediating  the  pain  sense  lie  most  superficially 
in  the  skin  and  those  for  the  warm  sense  the  deepest. 

Specific  Nerve  Energies  of  the  Cutaneous  Nerves. — Many 
attempts  have  been  made  to  determine  whether  the  doctrine  of 
specific  nerve  energies  applies  to  these  cutaneous  senses;  that  is, 
whether  each  sense  has  its  own  nerve  fibers  capable  of  giving  only  its 
own  quality  of  sensation.  The  evidence,  on  the  whole,  is  favorable 
to  this  view.  According  to  some  observers,  electrical  or  mechanical 
stimulation  of  the  different  points  calls  forth  for  each  its  character- 
istic reaction.  Donaldson  has  found  that  cocain  applied  to  the 
eye  or  throat  destroys  the  senses  of  pain  and  pressure,  but  leaves 
those  of  heat  and  cold,  which  again  supports  the  view  of  separate 
fibers  for  each  sense.  In  addition  there  are  a  number  of  interesting 


282  THE    SPECIAL    SENSES. 

pathological  cases  which  point  in  the  same  direction.  In  some 
lesions  of  the  cord — syringomyelia,  for  instance — the  senses  in  the 
skin  of  the  parts  below  are  dissociated, — that  is,  there  may  be  loss 
of  pain  and  temperature  in  a  certain  area  with  a  retention  of  the 
pressure  sense, — a  fact  which  indicates  that  these  senses  have  sepa- 
rate paths  and  therefore  separate  nerve-fibers.*  Still  more  inter- 
esting cases  of  dissociation  are  reported  as  a  result  of  the  com- 
pression of  peripheral  nerve  trunks.  Thus,  Barker  t  describes  his 
own  case,  in  which,  as  the  result  of  the  pressure  of  a  cervical  rib 
upon  some  of  the  cords  of  the  brachial  plexus,  there  was  a  region  in 
the  arm  lacking  in  the  pressure  and  temperature  senses,  but  retain- 
ing the  sense  of  pain.  He  quotes  other  cases  in  which  the  reverse 
dissociation  occurred,  pressure  sense  alone  remaining.  The  simplest 
explanation  of  these  facts  is  the  view  that  each  pressure,  pain, 
warm,  and  cold  spot  is  supplied  by  its  own  nerve  fiber,  and  that 
each,  when  stimulated,  reacts,  if  it  reacts  at  all,  only  with  its  own 
peculiar  quality  of  sensation.  According  to  this  view,  artificial 
stimulation,  if  properly  controlled,  of  the  trunks  of  the  nerves 
supplying  the  skin  should  be  capable  of  bringing  out  these  different 
sense  qualities.  Experiments  made  with  this  point  in  view  have 
not,  however,  been  very  successful.  Mechanical  or  electrical  stimu- 
lation of  the  ulnar  nerve,  for  instance,  gives  usually  only  pain  sensa- 
tions, although  if  the  stimulus  is  feeble  contact  sensations  are 
aroused.  The  method,  however,  is  probably  at  fault.  In  the  case 
of  amputated  fingers  or  limbs  a  more  decisive  result  is  obtained. 
As  is  well  known,  individuals  after  such  operations  may  for  many 
years  have  sensations  of  their  lost  fingers  or  limbs.  In  such  cases 
the  pressure  in  the  stump  of  the  wound  acting  upon  the  central  ends 
of  the  sensory  fibers  arouses  sensations  which  are  projected  in  the 
usual  way,  and  give  the  feeling  that  would  be  experienced  if  the 
lost  parts  were  still  there  and  were  stimulated  in  the  normal  manner. 
The  Temperature  Senses. — The  main  facts  regarding  the 
distribution  of  heat  and  cold  spots  have  been  determined,  but 
in  most  of  the  experiments  on  record  no  distinction  was  made 
between  protopathic  temperature  sensations  and  those  mediated 
by  the  epicritic  temperature  nerves.  It  is  difficult  to  adapt 
the  older  descriptions  to  this  newer  terminology,  but  when  not 
otherwise  specifically  stated  it  may  be  assumed  that  the  ep.icritic 
system  is  referred  to.  In  general,  the  cold  spots  are  more 
numerous  than  the  warm  spots,  and  react  more  promptly  to 
their  adequate  stimulus.  The  threshold  stimulus  varies  in 
different  parts  of  the  skin,  the  tip  of  the  tongue  requiring  the 

*  For  many  interesting  cases  of  dissociation  due  to  spinal  lesions  see  Head, 
"Brain,"  1906,537. 

t  Barker,  "  Journal  of  Experimental  Medicine,"  1,  348,  1896. 


CUTANEOUS    AND    INTERNAL   SENSATIONS.  283 

smallest  stimulus  to  arouse  a  sensation,  and  the  eyelids,  fore- 
head, cheeks,  lips,  limbs,  and  trunk  following  in  the  order 
named.  According  to  Goldscheider,  the  spots  on  most  portions 
of  the  skin  form  chains  that  have  a  somewhat  radiate  arrange- 
ment with  reference  to  the  hair  follicles.  The  temperature 
points  possess  each  its  adequate  stimulus,  that  for  the 
cold  spot  being  temperatures  lower  than  the  skin  or  of  the  terminal 
organ  of  the  cold  nerves,  that  for  the  heat  spots  temperatures  higher 
than  their  own.  From  the  standpoint  of  specific  nerve  ener- 
gies it  is  most  interesting  to  find  that  these  points,  particularly 
the  cold  spots,  may  be  stimulated  by  other  than  their  adequate 
stimuli.  Mechanical  and  electrical  stimulation  has,  in  the  hands  of 
several  observers,  been  efficient  in  causing  a  sensation  of  cold  upon 
a  cold  spot  and  of  heat  upon  a  warm  spot.  Some  chemical  stimuli 
are  also  effective.  Menthol  applied  to  the  skin  gives  a  cold  sensa- 
tion, while,  on  the  other  hand,  if  the  arm  be  plunged  into  a  jar  of 
carbon-dioxid  gas  a  distinct  warm  sensation  will  be  experienced. 
A  curious  effect  of  this  kind  is  what  is  known  as  the  paradoxical 
cold  reaction.  It  is  produced  by  applying  a  very  warm  object,  with 
a  temperature  of  40°  to  60°  C.,  to  a  cold  spot.  According  to 
Head  and  Rivers  this  reaction  is  rather  characteristic  of  the 
protopathic  temperature  fibers.  It  can  be  obtained,  for  example, 
from  the  glans  penis,  which  possesses  only  protopathic  sensibility, 
or  during  the  course  of  regeneration  of  a  severed  cutaneous 
nerve.  In  this  latter  condition  hot  objects  applied  to  a  cold 
spot  give  a  vivid  sensation  of  cold.  The  same  result  may  be 
felt  sometimes  at  the  instant  of  entering  a  hot  bath.  Many 
efforts  have  been  made  to  determine  whether  there  is  a  specific 
kind  of  end-organ  for  each  of  these  senses.  Numerous  observers 
have  cut  out  the  skin  from  cold  or  hot  spots  and  examined  the 
removed  part  carefully  by  histological  methods.  The  general 
result  has  been  that  no  distinctive  end-organs  have  been  found. 
Von  Frey,  however,  believes  that,  although  the  heat  spots  are 
supplied  simply  by  a  terminal  end  plexus,  the  cold  spots  in  some 
places  at  least  have  as  a  special  end-organ  the  end-bulbs  of 
Krause.  This  conclusion  is  based  upon  the  fact  that  these 
end-bulbs  are  found  in  places,  such  as  the  glans  penis  and  con- 
junctiva, where  the  cold  sense  is  especially  prominent  or  exclu- 
sively present. 

The  (Epicritic)  Sense  of  Pressure  or  Touch. — The  cutaneous 
pressure  points  are  smaller  and  more  numerous  than  the  cold 
or  warm  spots.  Von  Frey  has  shown  that  in  those  portions 
of  the  body  that  are  supplied  with  hairs  the  pressure  points 
lie  over  the  hair  follicles.  The  pressure  nerve-fibers,  in  fact, 
terminate  in  a  ring  surrounding  the  hair  follicle,  this  form 


284  THE    SPECIAL    SENSES. 

of  termination  serving  as  an  end-organ.  On  account  of  their 
position  they  are  stimulated  by  any  pressure  exerted  upon 
the  hair.  The  hair,  indeed,  acts  like  a  lever  and  transmits  any  pres- 
sure applied  to  it  with  increased  intensity,  acting,  therefore,  as  re- 
gards the  pressure  organ  somewhat  like  the  ear-bones  in  the  case 
of  the  endings  of  the  auditory  nerve.  In  parts  of  the  body  not 
furnished  with  hairs  the  tactile  or  Meissner  corpuscles  are  found 
and  these  structures  doubtless  function  as  pressure  end-organs. 
They  are  particularly  abundant  in  the  parts  of  the  hand  and  feet  in 
which  a  delicate  sense  of  pressure  is  present  in  spite  of  a  much  thick- 
ened epidermis.  It  has  been  estimated  that  for  the  entire  surface 
of  the  body,  excluding  the  head  region,  there  are  about  500,000 
of  these  pressure  points.  These  points  are  close  together  on  those 
parts,  such  as  the  tongue  and  fingers,  which  have  a  delicate  tactile 
sense  and  more  widely  scattered  where  the  sense  is  less  developed. 
The  Threshold  Stimulus  and  the  Localizing  Power. — The 
delicacy  of  the  sense  of  pressure  may  be  measured  by  determining 
the  minimal  pressure  necessary  to  arouse  a  sensation, — that  is, 
the  threshold  stimulus, — or  it  may  be  estimated  in  terms  of  the 
power  of  discriminating  two  contiguous  stimuli, — that  is,  the  mini- 
mal distance  that  two  points  must  be  apart  in  order  for  the  sensa- 
tions to  be  recognized  as  distinct.  The  two  methods  of  measure- 
ment do  not  coincide.  As  determined  by  the  threshold  stimulus, 
the  greatest  delicacy  is  exhibited  by  the  skin  of  the  face,  the  fore- 
head, and  temples.  According  to  the  older  methods  of  measure- 
ment, the  forehead  will  perceive  a  pressure  of  2  mgs.,  while  the  skin 
of  the  tips  of  the  ringers  needs  a  pressure  of  from  5  to  15  mgs.  to 
arouse  a  perceptible  sensation.  The  back  of  the  hand  or  the  arm 
.is  more  sensitive  from  this  standpoint  than  the  tips  of  the  fingers. 
When  measured  by  the  power  of  discriminating  two  points — 
that  is,  the  localizing  sense — the  tips  of  the  fingers  are  far  more 
sensitive  than  the  skin  of  the  face  or  of  the  arm.  This  latter  prop- 
erty, irl  fact,  stands  in  relation  to  the  closeness  of  the  pressure 
points  to  one  another.  The  localizing  sense  may  be  determined 
by  Weber's  method  of  using  a  pair  of  compasses  with  blunt  points. 
For  any  given  area  of  the  skin  the  power  of  discrimination  or  local- 
ization is  expressed  in  terms  of  the  number  of  millimeters  between 
the  two  points  at  which  they  are  just  distinguished  as  two  separate 
sensations  when  applied  simultaneously  to  the  skin.  Instruments 
made  for  this  purpose  are  designated  as  esthesiometers.  They 
carry  two  points  the  distance  of  which  apart  can  be  readily  adjusted 
and  read  off  on  a  scale.  The  most  satisfactory  form  of  esthesiom- 
eter  is  that  devised  by  von  Frey.  The  two  points  in  this  case  are 
made  by  long,  rather  stiff  hairs  whose  pressure  can  be  made  quite 
uniform.  According  to  the  older  measurements,  the  discriminat- 


CUTANEOUS    AND    INTERNAL    SENSATIONS.  285 

ing  sense  of  different  parts  of  the  skin  varies  greatly,  as  is  shown  by 
the  accompanying  table: 

Tip  of  the  tongue 1.1  mms. 

Tip  of  finger,  palmar  surface 2.3 

Second  phalanx  finger,  palmar  surface 4.5 

First  phalanx  finger,  palmar  surface 5.5 

Third  phalanx  finger,  dorsal  surface 6.8 

Middle  of  palm 8to9 

Second  phalanx  finger,  dorsal  surface 11.3 

Forehead 22.6 

Back  of  the  hand 31.6 

Forearm 40.6 

Sternum 45 

Along  the  spine 54 

Middle  of  neck  or  back 67.7 

The  tips  of  the  tongue  and  the  fingers  are,  therefore,  the  most 
delicate  surfaces,  and  that  the  tongue  surpasses  the  fingers  in  this 
respect  is  easily  within  the  experience  of  everyone  who  will  recall 
the  ease  with  which  small  objects  between  the  teeth  are  detected  by 
the  tongue  as  compared  with  the  fingers.  From  the  above  data  it 
is  evident  also  that  the  whole  skin  may  be  imagined  as  composed 
of  a  mosaic  of  areas  of  different  sizes,  the  sensory  circles  of  Weber, 
in  each  of  which  two  or  more  simultaneous  stimulations  of  the  pres- 
sure nerves  give  only  one  pressure  sensation.  The  size  of  these 
areas,  particularly  where  they  are  large,  may  be  reduced  by  practice, 
as  is  shown  by  the  increased  tactile  sensibility  of  the  blind.  The 
fact  that  we  can  recognize  two  simultaneous  pressure  stimuli  of  the 
skin  as  two  distinct  sensations  implies  that  the  two  sensations  have 
some  recognizable  difference  in  consciousness.  This  difference  is 
spoken  of  as  the  local  sign.  We  may  believe  that  every  sensitive 
point  upon  the  skin  has  its  own  distinctive  local  sign  or  quality,  and 
that  by  experience  we  have  learned  to  project  each  local  sign  more 
or  less  accurately  to  its  proper  place  on  the  skin  surface.  Two  points 
on  this  surface  that  are  a  great  distance  apart  are  easily  recognized 
as  different ;  but  as  we  bring  the  points  closer  together  the  difference 
becomes  less  marked  and  finally  disappears  when  the  distance 
corresponds  to  the  area  of  the  sensory  circle  for  the  part  of  the  skin 
investigated,  for  instance,  1  mm.  for  the  tongue,  22  mms.  for  the 
forehead,  etc.  The  ultimate  limit  of  the  power  of  discrimination 
was  assumed  by  Weber  to  depend  upon  the  area  of  distribution  of 
a  single  nerve  fiber.  Assuming  that  each  nerve  fiber  at  its  termi- 
nation spreads  over  a  certain  skin  area,  it  was  suggested  that  the 
size  of  this  area  forms  a  limit  to  the  power  of  discrimination, 
since  two  stimuli  within  it  would  affect  a  single  fiber  and  therefore 
would  give  a  single  sensation. 

This  view,  however,  has  not  been  supposed  to  accord  with  the 
facts  even  when  the  additional  supposition  was  made  that  the  local 


286  THE    SPECIAL    SENSES. 

signs  of  two  adjacent  fibers  may  not  be  distinct  enough  for  us  to 
recognize  them  as  separate  and  that  practically  there  must  be  a 
number  of  intervening  unstimulated  areas,  the  number  varying 
according  to  the  sensitiveness  of  the  area.  Von  Frey  has,  however, 
given  a  new  method  of  testing  the  localizing  sense  of  the  skin,  the 
results  of  which  seem  to  accord  with  this  anatomical  explanation. 
If  instead  of  applying  the  two  points  simultaneously  they  are 
applied  in  succession,  at  an  interval  of  one  second,  the  individual  can 
distinguish  the  difference  when  two  neighboring  pressure  points  are 
stimulated.  Each  pressure  point  in  the  skin,  therefore,  has  a  local 
sign,  which  enables  us  to  distinguish  it  from  all  others,  and  by  this 
method  the  ultimate  sensory  circles  on  the  skin  become  much 
smaller  than  when  measured  by  the  usual  method  of  Weber.  The 
center  of  each  is  a  pressure  point  and  the  area  is  determined  by  the 
distance  from  this  center  at  which  an  isolated  stimulation  of  this 
point  can  be  obtained.  It  seems  probable,  moreover,  that  each  of 
these  pressure  points  is  connected  to  the  brain  by  a  separate  nerve 
path,  possibly  a  single  fiber,  and  that  this  anatomical  arrangement 
determines  the  limitation  of  the  localizing  sense  for  different 
regions  of  the  skin. 

The  Pain  Sense. — Pain  is  probably  the  sense  that  is  most  widely 
distributed  in  the  body.  It  is  present  throughout  the  skin,  and 
under  certain  conditions  may  be  aroused  by  stimulation  of  sensory 
nerves  in  the  various  visceral  organs,  and  indeed  in  all  of  the  mem- 
branes of  the  body.  Our  knowledge  of  the  physiological  properties 
of  the  end-organs  and  nerves  mediating  this  sense  is  chiefly  limited 
to  the  skin,  and  for  cutaneous  pain  at  least  the  evidence,  as  stated 
above,  is  very  strongly  in  favor  of  the  view  that  there  exists  a  special 
set  of  fibers  which  have  a  specific  energy  for  pain.  All  recent  ob- 
servers agree  that  the  pain  sense  has  a  punctiform  distribution  in 
the  skin,  the  pain  points  being  even  more  numerous  than  the  pres- 
sure points.  The  threshold  stimulus  of  these  points  in  various 
regions  may  be  determined  by  von  Frey's  stimulating  hairs,  and 
experiments  of  this  kind  show,  as  we  should  expect,  that  it  varies 
greatly.  The  cornea,  for  instance,  gives  sensations  of  pain  with 
much  weaker  stimuli  than  in  the  case  of  the  finger  tips.  In  general, 
however,  the  threshold  stimulus  is  much  higher  for  the  pain  than 
for  the  pressure  points.  Histological  examination  of  the  pain  points 
indicates  that  there  is  no  special  end-organ,  the  stimulus  taking 
effect  upon  the  free  endings  of  the  nerve  fibers.  Any  of  the  usual 
forms  of  artificial  nerve  stimuli  may  affect  these  endings  if  of  suf- 
ficient intensity,  and,  as  is  well  known,  stimuli  applied  to  sensory 
nerve  trunks  affect  these  fibers  with  especial  ease.  A  temperature 
of  50°  to  70°  C.  applied  to  an  afferent  nerve  will  cause  violent  pain 
sensations,  but  has  no  effect  upon  the  motor  nerve  fibers  in  the  same 
trunk.  Mechanical  stimulation  gives  usually  only  pain  sensations, 


CUTANEOUS    AND    INTERNAL    SENSATIONS.  287 

and  the  results  of  inflammatory  changes,  as  in  neuritis  or  neural- 
gia, are  equally  marked. 

Localization  or  Projection  of  Pain  Sensations. — Under  normal 
conditions  cutaneous  pains  are  projected  with  accuracy  to  the  point 
stimulated,  and  it  is  possible  that  this  result  is  due  in  part  at  least 
to  the  training  acquired  in  connection  with  concomitant  (epicritic) 
pressure  sensations,  the  latter  acting  as  a  guide  or  aid  in  the  pro- 
jection. Thus  in  the  cases  referred  to  above,  in  which  a  portion 
of  the  skin  had  lost  the  sense  of  pressure  and  temperature,  but 
retained  that  of  pain,  it  was  found  that  the  localization  was  very 
incomplete.  Pain  arising  in  the  internal  organs,  on  the  contrary, 
is  located  very  inaccurately.  The  pain  from  a  severe  toothache, 
for  example,  may  be  projected  quite  diffusely  to  the  side  of  the  face. 
A  very  interesting  fact  in  this  connection  is  that  such  pains  are 
often  referred  to  points  on  the  skin  and  may  be  accompanied  by 
skin  areas  of  tenderness.  Pains  of  this  kind  that  are  misref erred 
to  the  surface  of  the  body  are  designated  as  reflected  pains.  It  has 
been  shown  by  Head  *  and  others  that  the  different  visceral  organs 
have,  in  this  respect,  a  more  or  less  definite  relation  to  certain 
areas  of  the  skin.  Pains  arising  from  stimuli  acting  upon  the 
intestines  are  located  in  the  skin  of  the  back,  loins,  and  abdomen 
in  the  area  supplied  by  the  ninth,  tenth,  and  eleventh  dorsal 
spinal  nerves;  pains  from  irritations  in  the  stomach  are  located 
in  the  skin  over  the  ensiform  cartilage;  those  from  the  heart  in  the 
scapular  region,  and  so  on.  The  explanation  offered  for  this 
misreference  is  that  the  pain  is  referred  to  the  skin  region  that  is 
supplied  from  the  spinal  segment  from  which  the  organ  in  question 
receives  its  sensory  fibers,  the  misreference  being  due  to  a  diffusion 
in  the  nerve  centers.  As  Head  expresses  it,  "when  a  painful 
stimulus  is  applied  to  a  part  of  low  sensibility  in  close  central 
connection  with  a  part  of  much  greater  sensibility  the  pain  pro- 
duced is  felt  in  the  part  of  higher  sensibility  rather  than  in  the  part 
of  lower  sensibility  to  which  the  stimulus  was  actually  applied." 
It  is  interesting  that  affections  of  the  serous  cavities — e.  g.,  the 
peritoneum — do  not  cause  reflected  pains  or  cutaneous  tenderness 
as  in  the  case  of  the  viscera.  Another  notable  fact  in  this  connec- 
tion is  the  occurrence  of  the  condition  known  as  allochiria.  When 
from  any  cause  one  or  other  of  the  cutaneous  senses  is  depressed 
in  a  given  area  stimulation  in  this  region  may  give  sensations 
which  are  referred  to  the  symmetrical  area  on  the  other  side  of 
the  body,  or,  if  this  also  is  involved,  it  may  be  referred  to  the  area 
next  above  or  below  in  the  spinal  order.  The  above  law, 
according  to  which  projection  is  made  to  the  area  of  high  sensi- 
bility most  closely  connected  with  the  area  of  low  sensibility, 
seems  to  hold  in  this  case  also. 

*  Head,  "  Brain,"  16,  1,  1893,  and  24,  345,  1901. 


288  THE    SPECIAL    SENSES. 

Muscular  or  Deep  Sensibility. — The  existence  of  a  special  set 
of  sensory  nerve-fibers  distributed  to  the  muscles  was  clearly 
recognized  by  some  of  the  older  physiologists.  Charles  Bell,* 
for  example,  says:  "Between  the  brain  and  the  muscles 
there  is  a  circle  of  nerves;  one  nerve  conveys  the  influence 
from  the  brain  to  the  muscle;  another  gives  the  sense  of  the 
condition  of  the  muscle  to  the  brain."  The  conclusive  proof 
of  the  existence  of  such  fibers,  however,  has  only  been  fur- 
nished within  recent  years.  It  has  been  demonstrated  that 
there  are  special  sensory  endings  in  the  muscles,  the  so-called 
muscle  spindles,  and  in  the  attached  tendons,  the  tendon  spindles 
or  tendon  organs  of  Golgi.  The  muscle  spindles  are  found  most 
frequently  in  the  neighborhood  of  the  tendons,  at  tendinous  inter- 
sections or  under  aponeuroses.  Sherrington*  has  shown  that  the 
nerve  fibers  in  them  do  not  degenerate  after  section  of  the  anterior 
roots  of  the  corresponding  spinal  nerves  and  are  therefore  derived 
from  the  posterior  roots.  In  the  muscles  of  the  limbs  he  estimates 
that  from  one-half  to  one-third  of  the  fibers  in  the  muscular  nerve 
branches  are  sensory,  and  that  most  of  these  sensory  fibers  end  in 
the  muscle  spindles.  On  the  physiological  and  clinical  side  facts  of 
various  kinds  have  accumulated  that  make  clear  the  existence  of 
this  group  of  sensory  fibers  and  emphasize  their  essential  importance 
in  the  co-ordination  of  our  muscular  movements.  It  has  been  shown 
that  stimulation  of  the  nerves  distributed  to  the  muscles  or  mechani- 
cal stimulation  of  the  muscles  themselves  causes  a  depressor  effect 
upon  blood-pressure,  thus  demonstrating  the  presence  of  afferent 
fibers  in  the  muscles.  As  described  in  the  section  upon  the  central 
nervous  system,  the  numerous  experiments  upon  the  effect  of  section 
of  the  posterior  and  lateral  funiculi  of  the  cord,  and  observations 
upon  the  results  of  pathological  lesions  of  the  posterior  funiculi 
(tabes  dorsalis)  give  results  which  are  interpreted  to  mean  that 
fibers  of  muscular  sensibility  form  the  most  important  group  in 
the  posterior  funiculi  and  constitute,  as  well,  perhaps,  the  long, 
ascending  fibers  in  the  cerebellospinal  fasciculus  in  the  lateral 
funiculi.  It  is  believed,  therefore,  that  our  so-called  voluntary 
muscles  are  richly  supplied  with  afferent  fibers  and  that  the  im- 
pulses carried  by  these  fibers  to  the  brain  are  necessary  for  the 
proper  contraction  of  the  muscles,  and  particularly  for  the  ade- 
quate combination  of  the  contractions  of  groups  of  muscles  in 
the  co-ordinated  movements  of  equilibrium.  Indeed,  section  of 
the  posterior  roots  of  the  spinal  nerves  supplying  a  given  region 
is  followed  by  a  loss  of  control  of  the  muscles  in  this  region 
hardly  less  complete  than  the  paralysis  produced  by  direct 

*  Bell,  "  The  Nervous  System  of  the  Human  Body,"  third  edition,  Lon- 
don, 1844,  p.  200. 

t  Sherrington,  "  Journal  of  Physiology,"  17,  237,  1874. 


CUTANEOUS    AND    INTERNAL    SENSATIONS.  289 

section  of  the  anterior  roots;  the  muscles  not  only  lose  their 
tonicity  in  consequence  of  the  dropping  out  of  the  reflex  sensory 
stimuli  from  the  skin  and  muscles  of  the  region,  but  they  are 
apparently  withdrawn  from  voluntary  control  in  spite  of  the 
maintenance  of  their  normal  motor  connections.  Within  the 
central  nervous  system  the  afferent  nerve-fibers  of  the  muscles  end 
in  part  in  the  cerebellum  and  in  part  pass  forward,  by  way  of  the 
median  fillet,  to  end  in  the  cerebrum.  In  the  cerebrum  they  end  in 
the  cortex  of  the  parietal  lobe  in  the  region  of  the  posterior  central 
convolution.  There  is  reason  to  believe  that  this  cortical  sense 
area  of  the  muscle  sense  is  connected  by  association  fibers  with 
the  motor  areas  lying  anterior  to  the  central  fissure  of  Rolando, 
and  we  have  thus  a  reflex  arc — or,  as  Bell  expressed  it,  a  circle 
of  nerves  between  the  muscles  and  the  brain.  It  is  probable 
that  a  similar  arc  or  circle  is  formed  by  the  connections  through 
the  cerebellum,  and  still  a  third  one  of  a  lower  order  by  the 
connections  in  the  spinal  cord.  In  the  higher  animals  the 
impulses  received  in  the  cerebellum  through  the  fibers  of  muscle 
sense,  in  connection  with  those  received  from  the  semicircular 
canals  and  vestibular  sacs  of  the  ear,  furnish  the  afferent  element 
in  the  reflex  cerebellar  control  of  muscular  movements,  particularly 
of  the  synergetic  combinations  necessary  in  locomotion.  Through 
the  circle  or  arc  in  the  cortex  of  the  cerebrum  it  may  be  supposed 
that  our  characteristic  voluntary  movements  are  affected,  and 
it  may  be  doubted  whether  a  so-called  voluntary  contraction 
can  be  made  when  this  circle  is  broken  on  the  sensory  side. 
Whether  or  not  this  latter  suggestion  is  true,  it  seems  to  be 
beyond  doubt  that  adequately  controlled  voluntary  movements 
depend  for  their  adaptation  upon  the  inflow  of  afferent  impulses 
along  the  fibers  of  muscle  sense.  We  have  a  certain  conscious- 
ness of  the  condition  of  our  muscles  at  all  times,  and  if  we  were 
deprived  of  this  knowledge  we  should  be  unable  to  control  them 
properly,  perhaps  unable  to  use  them  voluntarily. 

The  Quality  of  the  Muscular  Sensibility. — Under  the  term 
muscular  sensibility  in  its  wide  sense  we  must  understand  the 
sensibility  mediated  by  the  afferent  fibers  from  the  muscles, 
the  tendons,  ligaments,  and  joints.  The  quality  of  these  deep 
sensations  is  of  several  kinds — we  have  first  of  all  the  deep 
pressure  sensibility  (see  p.  279),  which  gives  a  definite  conscious 
reaction  that  is  well  localized.  It  is  usually  projected  to  the 
exterior  and  is  not  consciously  separated  from  the  tactile  or 
pressure  sensations  of  the  skin.  We  probably  make  much  use 
of  this  sensibility  in  judging  the  weight  and  resistance  of  bodies. 
Muscular  sensibility  proper  is  that  ill-defined  consciousness 
which  we  possess  of  the  condition  and  position  of  our  muscles 
19 


290  THE  SPECIAL  SENSES. 

or  of  the  joints  or  limbs  moved  by  them.  It  includes  also  the 
sense  of  passive  position,  and  the  sense  of  effort  and  of  the  spatial 
relations  of  the  limbs  in  motion  or  at  rest.  When  the  afferent 
fibers  from  the  muscles  and  joints  are  traced  into  the  central 
nervous  system,  some  of  them,  it  will  be  remembered,  enter  the 
tracts  of  Flechsig  and  Gower  and  end  in  the  cerebellum,  while 
u  oners  pass  up  the  cord  in  the  posterior  funiculi,  enter  the  lemniscus*, 
and  terminate  eventually  in  the  cerebral  cortex  in  the  post- 
Rolandic  region.  Our  conscious  muscular  sensations  are  mediated 
presumably  by  this  latter  group.  The  untrained  person  scarcely 
recognizes  the  existence  of  these  sensations,  but  they  are  evident 
enough  upon  analysis,  and  it  is  most  certain  that  they  take  a 
fundamental  part  in  regulating  our  movements.  In  our  estima- 
tions of  the  extent  of  the  muscular  contractions  they  form  the 
chief  sensory  basis,  and  in  this  way  they  may  indirectly  furnish 
us  with  data  for  perceptions  and  judgments  of  various  kinds. 
Doubtless,  also,  this  sense  takes  an  essential  part  in  the  primitive 
formation  of  our  conceptions  of  space,  since  it  may  be  assumed 
that  the  continual  movements  of  the  extremities  furnish  in  con- 
nection with  our  visual  and  tactile  impressions  essential  data 
upon  which  we  build  our  perceptions  of  distance  and  size,  our 
judgments  of  spatial  relations.  As  is  explained  in  the  chapter 
on  the  Physiology  of  the  Ear,  the  sensations  from  the  semi- 
circular canals  and  vestibular  sacs  co-operate  in  giving  data  for 
these  fundamental  conceptions,  and  it  is  not  possible  for  us  to 
disentangle  the  parts  taken  by  these  senses  separately  in  building 
up  our  knowledge  of  the  external  world. 

Sensations  of  Hunger  and  Thirst. — Hunger  and  thirst  are 
typical  interior  (or  common)  sensations.  We  feel  them  as  changes 
in  ourselves,  although  the  sensations  are  of  such  a  vague  character 
that  it  is  difficult  to  analyze  them  successfully  by  methods  of  intro- 
spection. The  feeling  that  we  designate  commonly  as  hunger  or 
appetite  occurs  normally  at  a  certain  time  after  meals,  and  it  is 
referred  or  projected  more  or  less  definitely  to  the  region  of  the 
stomach.  When  the  sensation  is  not  satisfied  by  the  ingestion  of 
food,  it  increases  in  intensity  and  the  individual  experiences  the 
pangs  of  hunger.  The  testimony  of  those  who  have  starved  for 
long  periods,  as  well  as  the  experience  of  professional  fasters,  indi- 
cates that  these  pangs  after  a  few  days  diminish  in  strength  and  may 
finally  disappear,  so  that  prolonged  starvation  is  not  accompanied 
necessarily  by  physical  suffering.  The  older  observers  made  a 
distinction  between  a  hunger  supposed  to  be  due  to  conditions  in 
the  stomach  and  a  hunger  due  to  insufficient  nutrition  in  the  body 
at  large.  Whether  or  not  sensations  of  this  quality  can  arise  from 
impoverished  nutrition  of  the  tissues  in  general  has  been  a  matter 
of  some  dispute.  There  are  some  facts  which  indicate  that  a 


CUTANEOUS    AND    INTERNAL    SENSATIONS.  291 

general  or  somatic  hunger  may  exist,  for  example,  the  continued 
hunger,  in  spite  of  ample  food,  which  may  be  present  in  a  condition 
such  as  diabetes,  or  such  a  case  as  that  described  by  Hertz,*  in 
which  a  patient  with  an  intestinal  fistula  through  which  most  of  the 
food  escaped  complained  of  constant  hunger,  although  his  stomach 
was  filled  with  food.  It  is  possible,  of  course,  that  in  such  cases 
the  sensations  of  hunger  are  not  produced  by  general  changes  in  the 
tissues,  but  are  due  to  some  chemical  change  in  the  blood  that 
affects  the  hunger  apparatus  of  the  stomach.  What  we  usually 
mean  by  hunger  is  a  sensation  that  is  referable  to  changes  in  the 
stomach  and  disappears  normally  when  the  stomach  is  supplied 
with  food.  Cannon  a'nd  Washburn*  have  shown  that  when  the 
stomach  is  empty  the  hunger  sensations  may  appear  and  disappear 
at  certain  intervals,  and  they  have  demonstrated  experimentally 
that  the  appearance  of  a  hunger  pain  is  simultaneous  with  a  con- 
traction of  the  musculature  of  the  stomach.  They  propose  the 
theory  that  hunger  sensations  or  hunger  pains  are  caused  by  con- 
tractions of  the  stomach,  the  contractions  affecting  presumably 
some  as  yet  undescribed  sensory  apparatus.  Carlson  t  has  reported 
observations  upon  a  man  with  a  permanent  gastric  fistula,  which 
corroborate  the  results  of  Cannon  and  Washburn.  As  soon  as 
the  stomach  is  empty  these  hunger  contractions  make  their  appear- 
ance, but  mechanical  or  chemical  stimulation  of  the  mucous 
membrane  of  the  mouth,  esophagus,  or  stomach  causes  them  to 
disappear  through  a  reflex  inhibition.  The  efferent  fibers  con- 
cerned in  this  inhibition  run  in  the  splanchnic  nerves.  Since  the 
hunger  contractions  occur  after  section  of  both  vagi  and  splanch- 
nics,  it  is  evident  that  the  essential  mechanism  concerned  is 
wholly  intrinsic,  involving,  probably,  the  local  nerve  plexuses 
in  the  walls  of  the  stomach.  The  vagi  exert  a  tonic  influence  on 
the  apparatus,  while,  as  just  stated,  its  activity  is  readily  in- 
hibited through  the  splanchnic  paths.  Since  the  hunger  pains 
and  the  hunger  contractions  disappear  when  food  is  eaten,  and 
while  the  stomach  is  in  active  digestion,  it  seems  evident  that  the 
ordinary  movements  of  the  stomach  during  digestion  are  of  a 
different  order  from  those  contractions  that  cause  hunger  pains. 
It  is  suggested  that  the  digestive  contractions  involve  mainly  the 
pyloric  musculature,  while  the  hunger  contractions  are  initiated  at 
the  cardiac  end  and  involve  the  whole  stomach.  According  to  the 
descriptions  given  it  would  seem  that  as  the  stomach  empties  itself 
the  ordinary  digestive  contractions  give  place  to  the  hunger  con- 
tractions. "The  digestive  contractions  of  the  filled  stomach  pass 

*  Hertz,  "The  Sensibility  of  the  Alimentary  Canal,"  London,  1911. 

t  Cannon  and  Washburn,  "American  Journal  of  Physiology,"  29,  441, 1912. 

t  Carlson,  "The  Control  of  Hunger  in  Health  and  Disease,"  Chicago,  1916. 


292  THE    SPECIAL    SENSES. 

gradually  over  in  to  the  hunger  contractions  of  the  empty  stomach." 
But  it  is  not  clear  why  the  latter  series  of  contractions  should  give 
rise  to  conscious  sensations  while  the  former  series  lacks  this  ac- 
companiment. Some  confusion  has  existed  in  regard  to  the  sig- 
nificance of  the  terms  "hunger"  and  "appetite."  Most  writers 
have  been  inclined  to  use  these  terms  to  indicate  different  degrees 
of  activity  of  the  same  sensory  apparatus,  appetite  being  employed 
to  describe  the  milder  forms  of  hunger  as  contrasted  with  the 
stronger  and  more  disagreeable  sensations  designated  as  hunger 
pains  or  hunger  pangs.  Other  authors  consider  that  hunger 
and  appetite  constitute  two  different  sensations  mediated  pre- 
sumably by  two  different  physiological  mechanisms.  Thus, 
Cannon  and  Washburn  define  appetite  as  a  kind  of  pleasurable 
mental  state  connected  with  stimulation  of  the  nerves  of  taste  or 
odor  and  dependent  upon  past  associations  of  an  agreeable  char- 
acter. Carlson*  also  separates  sharply  the  two  sensations. 
The  sensory  apparatus  for  hunger  lies  in  the  walls  of  the  stomach, 
probably  in  the  muscular  coats,  and  is  stimulated  by  the  contrac- 
tions of  the  musculature.  The  sensations  aroused  are  more  or  less 
disagreeable.  Appetite,  on  the  contrary,  is  an  entirely  pleasant 
sensation  aroused  in  part  through  the  sensory  nerves  of  taste 
and  smell,  but  also  by  sensory  fibers  in  the  gastric  mucosa.  This 
gastric  component  of  the  appetite-sense  explains  the  increased 
appetite  observed  sometimes  at  the  beginning  of  a  meal  after 
partaking  of  some  palatable  food.  Under  ordinary  conditions  of 
life  the  regulation  of  the  amount  and  quality  of  the  food  necessary 
to  the  proper  nutrition  of  the  body  and  the  maintenance  of  body 
equilibrium  is  effected  through  the  sense  of  hunger  or  of  hunger  and 
appetite.  Its  striking  influence  upon  the  body  at  large  is  well  illus- 
trated in  the  case  of  animals  (pigeons,  dogs)  deprived  of  their  cere- 
brum. During  the  period  of  fasting  these  animals  show  all  the  ex- 
ternal signs  of  hunger,  and  keep  in  continual,  restless  movement 
that  seems  to  imply  a  constantly  acting  sensory  stimulus.  The 
complexity  of  the  nervous  apparatus  that  controls  the  appetite  is 
shown  by  many  facts  from  the  experiences  of  life  and  from  the 
results  of  laboratory  investigations.  For  example,  it  is  found  that 
large  amounts  of  gelatin  in  the  diet,  although  at  first  accepted  will- 
ingly, soon  provoke  a  feeling  of  dislike  and  aversion  to  this  particu- 
lar foodstuff  which  cannot  be  overcome.  An  animal  will  starve 
-rather  than  use  the  gelatin,  although  all  of  our  direct  physiological 
evidence  would  indicate  that  this  substance  is  an  efficient  food, 
playing  much  the  same  part  as  the  fats  or  carbohydrates.  A  fact  of 
this  kind  indicates  that  the  sensory  apparatus  of  the  appetite  is 
influenced  in  some  specific  way  by  the  metabolism  of  this  particu-. 
*  Carlson  and  Braafladt,  "American  Journal  of  Physiology,"  36,  153, 1914. 


CUTANEOUS   AND    INTERNAL    SENSATIONS.  293 

lar  material.  So  also  the  feeling  of  satiety  and  aversion  for 
food  that  follows  overfeeding  indicates  something  more  than  a 
simple  removal  of  the  sensations  of  hunger;  it  implies  an  active 
state,  due  possibly  to  the  excitation  of  sensory  fibers  of  a  different 
character. 

The  Sense  of  Thirst. — Our  sensations  of  thirst  are  projected 
more  or  less  accurately  to  the  pharynx,  and  the  facts  that  we  know 
would  seem  to  indicate  that  the  sensory  nerves  of  this  region  have 
the  important  function  of  mediating  this  sense.  The  water  con- 
tents of  the  body  are  subject  to  great  changes.  Through  the  lungs, 
the  skin,  and  the  kidneys  water  is  lost  continually  in  amounts  that 
vary  with  the  conditions  of  life.  This  loss  affects  the  blood  directly, 
but  is  doubtless  made  good,  so 'far  as  this  tissue  is  concerned,  by  a 
call  upon  the  great  mass  of  water  contained  in  the  storehouse  of  the 
tissues.  To  restore  the  body  tissues  to  their  normal  equilibrium 
in  water  we  ingest  large  quantities,  and  the  control  of  this  regula- 
tion is  effected  through  the  sense  of  thirst.  We  know  little  or 
nothing  about  the  nervous  apparatus  involved;  but  it  may  be 
assumed  that  when  the  water  content  falls  below  a  certain  amount 
the  nerve  fibers  in  the  pharyngeal  membrane  (fibers  of  the  glosso- 
pharyngeal  nerve)  are  stimulated  and  give  us  the  sensation  of 
thirst.  That  we  have  in  this  membrane  a  special  end-organ  of 
thirst  is  indicated,  moreover,  by  the  fact  that  local  drying  in  this 
region,  from  dry  or  salty  food,  or  dry  and  dusty  air,  produces  a 
sensation  of  thirst  that  may  be  appeased  by  moistening  the  mem- 
brane with  a  small  amount  of  water  not  in  itself  sufficient  to  relieve 
a  genuine  water  need  of  the  body.  Our  normal  thirst  sensations 
might  be  designated,  therefore,  as  pharyngeal  thirst,  to  indicate 
the  probable  origin  of  the  sensory  stimuli.  Prolonged  deprivation 
of  water,  however,  must  affect  the  water  content  of  all  the  tissues, 
and  under  these  conditions  sensations  are  experienced  whose  quality 
is  not  that  of  simple  thirst  alone,  but  of  pain  or  suffering.  All  ac- 
counts agree  that  complete  deprivation  of  water  for  long  periods 
induces  intense  discomfort,  anguish,  and  possibly  mental  troubles, 
and  we  may  suppose  that  under  these  conditions  sensory  nerves 
are  stimulated  in  many  tissues,  and  that  the  metabolism  in  the  ner- 
vous system  in  addition  is  directly  affected  by  the  loss  of  water.*  It 
is  interesting  to  note  that  while  in  diseases  due  to  a  general  infec- 
tion, loss  of  appetite,  anorexia,  is  a  frequent  symptom,  there  is  no 
corresponding  loss  of  the  sense  of  thirst.  Even  in  hydrophobia 
the  patient  experiences  the  sensations  of  thirst,  although  unable 
to  drink  water. 

*  According  to  an  interesting  account  of  death  from  voluntary  starvation, 
quoted  by  Hertz  (loc.  cit.),  there  comes  a  time  at  which  neither  thirst  nor 
hunger  causes  any  distress. 


CHAPTER  XVI. 
SENSATIONS  OF  TASTE  AND  SMELL. 

The  sense  of  taste  is  mediated  by  nerve  fibers  distributed  to 
parts  of  the  buccal  cavity  and  particularly  to  parts  of  the  tongue. 
The  most  sensitive  regions  are  the  tip,  the  borders,  and  the  posterior 
portion  of  the  dorsum  of  the  tongue  in  the  region  of  the  circum- 
vallate  papillae.  Taste  buds  and  a  sense  of  taste  are  described  also 
for  the  soft  palate,  the  epiglottis,  and  even  for  the  larynx.  The 
sense  is  not  present  uniformly  over  the  entire  dorsum  of  the  tongue. 
On  the  contrary,  it  has  an  irregular,  punctiform  distribution  over 
most  of  this  region  with  the  exception  of  the  parts  mentioned  above. 

The  Nerves  of  Taste. — The  anterior  two-thirds  of  the  tongue 
are  supplied  with  sensory  fibers  from  the  lingual  nerve,  a  branch 
of  the  inferior  maxillary  division  of  the  fifth  nerve,  and  the  posterior 
third  from  the  glossopharyngeal.  The  taste  fibers  for  these  regions, 
therefore,  are  supplied  immediately  through  these  nerves.  It  has 
been  shown,  moreover,  that  the  taste  fibers  carried  in  the  lingual 
are  brought  to  it  through  the  chorda  tympani  nerve,  which  arises 
from  the  seventh  cranial  nerve  and  joins  the  lingual  soon  after 
emerging  from  the  tympanic  cavity  of  the  ear.  There  has  been 
much  discussion  as  to  the  origin  of  these  taste  fibers  from  the  brain. 
At  first  sight  it  would  seem  that  the  fibers  for  the  posterior  third 
of  the  tongue  must  have  their  origin  from  the  brain  in  the  glosso- 
pharyngeal and  those  for  the  anterior  two-thirds  in  the  sensory 
portion  of  the  facial.  Many  surgeons  have  reported,  however,  that 
complete  extirpation  of  the  semilunar  ganglion  of  the  fifth  nerve 
is  followed  by  complete  loss  of  taste  in  the  corresponding  side  of 
the  tongue,  and  others  have  described  a  loss  of  taste  for  the 
anterior  two-thirds  following  a  similar  operation.  Some  authors 
have  asserted,  therefore,  that  all  the  taste  fibers  originate 
or  rather  end  in  the  sensory  nucleus  of  the  fifth,  while  others 
believe  that  the  fibers  running  in  the  chorda  tympani,  at  least, 
take  their  origin  in  the  fifth  nerve.  It  is  supposed  by  these 
authors  that  the  fibers  reach  the  semilunar  ganglion  by  a  cir- 
cuitous route,  as  is  indicated  in  the  diagram  given  in  Fig.  120. 
Those  that  run  in  the  lingual  and  chorda  tympani  nerves  are 
assumed  to  pass  to  the  ganglion  by  way  of  the  great  superficial 
petrosal  and  Vidian  nerves  and  the  sphenopalatine  ganglion, 
while  those  that  are  contained  in  the  glossopharyngeal  reach 

294 


SENSATIONS    OF    TASTE    AND    SMELL. 


295 


the  same  ganglion  through  the  tympanic  nerve,  the  small  super- 
ficial petrosal,  and  the  otic  ganglion.  A  report  by  Gushing* 
of  the  results  of  removal  of  the  Gasserian  ganglion  in  thirteen 
cases  throws  much  doubt  upon  these  views.  This  author  made 
careful  examinations  of  the  sense  of  taste,  not  only  immediately 
after  the  operation,  but  for  a  long  period  subsequently.  He 
states  that  in  no  case  was  there  any  effect  upon  the  sense  of  taste 
in  the  posterior  third  of  the  tongue.  We  may  believe,  therefore, 
that  the  taste  fibers  of  this  part  arise  immediately  from  the  ganglion- 
cells  in  the  petrosal  ganglion  and  enter  the  brain  with  the  roots  of 
the  nerve  to  terminate  in  its  sensory  nucleus  in  the  medulla. 


UuxWul'mt 


Fig.  120. — Schema  to  show  the  course  of  the  taste  fibers  from  tongue  to  brain. — 
(Cushing.)  The  dotted  lines  represent  the  course  as  indicated  by  Cushing's  observations. 
The  full  black  lines  indicate  the  paths  by  which  some  authors  have  supposed  that  these 
fibers  enter  the  brain  in  the  trigeminal  nerve. 

Regarding  the  anterior  two-thirds  of  the  tongue,  the  lingual  region, 
it  was  found  that  in  some  cases  there  was  at  first  a  loss  of  acuity  of 
taste  or  even  an  entire  disappearance  of  the  sense,  but  subsequently 
it  returned.  It  would  seem,  therefore,  that  the  loss  of  taste  de- 
scribed after  removal  of  the  Gasserian  ganglion  is  an  incidental 
result  the  cause  of  which  is  not  entirely  clear.  Gushing  attributes 
it  to  a  postoperative  degeneration  and  swelling  in  the  fibers  of  the 
lingual  nerve,  which  affect  the  conductivity  of  the  intermingled 
fibers  of  the  chorda  tympani.  Since,  however,  there  is  no  perma- 

*  Gushing,  "  Bulletin  of  the  Johns  Hopkins  Hospital,"  14,  71,  1903.  Gives 
also  the  surgical  literature. 


296 


THE    SPECIAL    SENSES. 


nent  loss  of  taste  in  this  region,  it  follows  that  the  taste  fibers 
do  not  pass  through  the  Gasserian  ganglion.  We  may  assume, 
therefore,  that  they  originate  directly  in  the  nerve  cells  of  the 
geniculate  ganglion  and  enter  the  brain  with  the  fibers  of  the 
intermediate  nerve  (n.  intermedius  Wrisbergii). 

The  End-organ  of  the  Taste  Fibers. — In  the  circumvallate 
papillae,  in  some  of  the  fungiform  papillae,  and  in  certain  portions 
of  the  fauces,  palate,  epiglottis,  or  even  the  vocal  cords  there  are 
found  the  organs  known  as  taste  buds  which  are  believed  to  act 
as  peripheral  organs  of  taste.  These  curious  structures  are  repre- 
sented in  Fig.  121.  They  are  oval  bodies  with  an  external  layer 
of  tegmental  or  cortical  cells,  and  they  contain  in  the  interior  a 

number  of  elongated  cells 
each  of  which  ends  in  a  hair- 
like  process  which  projects 
through  the  central  taste 
pore  of  the  organ.  These 
latter  cells  may  be  consid- 
ered as  the  true  sense  cells ; 
the  hair-like  process  con- 
stitutes probably  the  part 
that  is  stimulated  directly 
by  sapid  substances.  The 
impulse  thus  aroused  is 
communicated  through  the 
body  of  the  cell  to  the 
endings  of  the  taste  fibers 
which  terminate  around 
these  cells  by  terminal 
arborizations  of  the  same 
general  type  as  in  the  case 
of  the  hair  cells  in  the 
cochlea. 

Classification  of  Taste  Sensations. — Our  taste  sensations 
are  very  numerous,  but  it  has  been  shown  that  there  are  four 
primary  or  fundamental  sensations, — namely,  sweet,  bitter,  acid, 
and  salty,  and  that  all  other  tastes  are  combinations  of  these 
primary  sensations,  or  combinations  of  one  or  more  of  them  with 
sensations  of  odor  or  with  sensations  derived  from  stimulation  of 
the  so-called  nerves  of  common  sensibility  in  the  tongue.  Thus, 
the  taste  of  pepper  may  be  resolved  into  a  slight  odor  sensation 
and  a  sensation  due  to  stimulation  of  the  fibers  of  general  sensi- 
bility,— that  is,  it  gives  no  taste  sensation  proper.  The  taste  of 
alum  may  be  considered  as  a  combination  of  a  salty  taste  with 
common  sensibility.  Combinations  of  sweet  and  acid  tastes,  sweet 


tatory  pore:  «,  gustatory  cell;  r,  sustentacular 
cell;  m,  leucocyte  containing  granules;  e,  super- 
ficial epithelial  cells;  n,  nerve  fibers. 


SENSATIONS    OF   TASTE   AND    SMELL.  297 

and  bitter  tastes,  etc.,  form  a  part  of  our  daily  experience,  and 
in  the  fused  or  compound  sensation  that  results  from  such  com- 
binations one  may  usually  recognize  without  difficulty  the  con- 
stituent parts.  The  seemingly  great  variety  of  our  taste  sensations 
is  largely  due  to  the  fact  that  we  confuse  them  or  combine  them 
with  simultaneous  odor  sensations.  Thus,  the  flavors  in  fruits  and 
the  bouquet  of  wines  are  due  to  odor  sensations  which  we  designate 
ordinarily  as  tastes,  since  they  are  experienced  at  the  time  these 
objects  are  ingested.  If  care  is  taken  to  shut  off  the  nasal  cavities 
during  the  act  of  ingestion  even  imperfectly,  as  by  holding  the 
nose,  the  so-called  taste  disappears  in  large  measure.  Very  dis- 
agreeable tastes  are  usually,  as  a  matter  of  fact,  due  to  unpleasant 
odor  sensations.  On  the  other  hand,  some  volatile  substances 
which  enter  the  mouth  through  the  nostrils  and  stimulate  the 
taste  organs  are  interpreted  by  us  as  odors.  The  odor  of  chloro- 
form, for  instance,  is  largely  due  to  stimulation  of  the  sweet  taste 
in  the  tongue. 

Distribution  and  Specific  Energy  of  the  Fundamental 
Taste  Sensations. — Regarding  the  distribution  of  the  funda- 
mental taste  sensations  over  the  tongue  and  palate  there  seem 
to  be  many  individual  differences.  In  general,  however,  it  may 
be  said  that  the  bitter  taste  is  more  developed  at  the  back  of 
the  tongue  and  the  adjacent  or  posterior  regions;  at  the  tip  of 
the  tongue  the  bitter  sense  is  less  marked  or  in  cases  may  be  absent 
altogether.  On  the  contrary,  in  this  latter  region  the  sweet  taste 
is  well  developed.  On  this  account  it  may  happen  that  substances 
which  when  first  taken  into  the  mouth  give  a  not  unpleasant  sweet 
taste  subsequently  when  swallowed  cause  disagreeably  bitter  sen- 
sations, like  the  little  book  of  the  evangelist,  which  in  the  mouth 
was  "sweet  as  honey,  and  as  soon  as  I  had  eaten  it,  my  belly  was 
bitter."  Oehrwall  *  has  made  an  interesting  series  of  experiments 
in  which  he  stimulated  separately  a  number  of  fungiform  papillae 
on  the  surface  of  the  tongue.  Each  papilla  was  stimulated  sepa- 
rately for  its  fundamental  taste  sense  of  sweet,  bitter,  and  acid, 
by  using  drops  of  solutions  of  sugar,  quinin,  and  tartaric  acid.  Of 
the  125  papillae  thus  examined,  27  gave  no  reaction  at  all,  although 
sensitive  to  pressure  and  temperature.  In  the  98  papillae  that 
reacted  to  the  sapid  stimulation  it  was  found  that  60  gave  taste 
sensations  of  all  three  qualities,  4  gave  only  sweet  and  bitter,  7  only 
bitter  and  acid,  12  only  sweet  and  acid,  12  only  acid,  and  3  only 
sweet.  None  was  found  to  give  only  a  bitter  sensation.  These 
facts  bear  directly  upon  the  question  of  the  specific  energy  of  the 
taste  fibers.  It  is  possible  that  the  four  fundamental  taste  qualities 
may  be  mediated  by  four  different  end-organs  and  four  separate 
*  Oehrwall,  "Skandinavisches  Archiv  f.  Physiologic,"  2,  1,  1890. 


298  THE  SPECIAL  SENSES. 

sets  of  nerve  fibers,  each  giving,  when  stimulated,  only  its  own 
quality  of  sensation.  On  the  other  hand,  it  is  possible  that  one  and 
the  same  nerve  fiber  might  give  different  qualities  of  sensation 
according  to  the  nature  and  mode  of  action  of  the  sapid  substances. 
The  fact,  as  shown  by  Oehrwall's  experiments,  that  there  are  sensory 
spots  upon  the  tongue  which  will  not  react  to  some  kinds  of  sapid 
substance,  but  do  react  to  others,  and  perhaps  only  to  one  particular 
kind,  speaks  strongly  in  favor  of  the  view  that  there  are  different 
end-organs  and  nerve  fibers  for  each  fundamental  taste.  This  view 
is  still  further  supported  by  the  fact  that  certain  chemically  pure  sub- 
stance •>  give  different  tastes  according  to  the  part  of  the  tongue 
upon  which  they  are  placed.  Thus,  sodium  sulphate  (Guyot)  may 
taste  salty  upon  the  tip  of  the  tongue  and  bitter  when  placed  upon 
the  posterior  part.  A  better  instance  still  is  given  by  solutions  of 
a  bromin  substitution  product  of  saccharin,  the  chemical  name 

!PO 
oX  ^NH. 
feO2/ 

When  this  substance  is  placed  upon  the  tip  of  the  tongue  it  gives  a 
sweet  sensation,  while  upon  the  posterior  region  it  gives  only  a  bitter 
taste  together  with  a  sensation  of  astringency  (Ho well  and  Kastle). 
Extracts  of  the  leaves  of  a  tropical  plant,  Gymnema  silvestre,  applied 
to  the  tongue,  destroy  the  sense  of  taste  for  sweet  and  bitter  sub- 
stances (Shore),  and  this  fact  may  be  explained  most  satisfactorily 
by  assuming  that  this  substance  exercises  a  selective  action  upon 
taste  terminals  in  the  tongue,  paralyzing  those  for  the  bitter 
and  the  sweet  substances.  Finally,  the  fact  that  electrical,  me- 
chanical, or  chemical  stimulation  of  the  chorda  tympani,  where  it 
passes  through  the  tympanic  cavity,  may  arouse  taste  sensations  is 
proof  that  the  taste  sensation  in  general  is  not  due  to  a  peculiar  kind 
of  impulse  that  can  be  aroused  only  by  the  action  of  sapid  bodies 
upon  the  terminals  in  the  tongue,  but,  on  the  contrary,  that  it  is  a 
specific  energy  of  these  fibers,  and  depends  for  its  quality,  there- 
fore, upon  the  specific  reaction  of  the  terminations  in  the  brain. 

Method  of  Sapid  Stimulation. — In  order  that  sapid  substances 
may  react  upon  the  taste  terminals  it  is  necessary,  in  the  first  place, 
that  they  shall  be  in  solution.  It  is  impossible  to  taste  with  a  dry- 
tongue.  We  may  assume,  therefore,  that  the  stimulation  consists 
essentially  in  a  chemical  reaction  between  the  sapid  substance  and 
the  terminal  of  the  taste  fiber, — for  instance,  the  hair  process  of 
the  sense  cells  in  the  taste  buds, — and  the  question  naturally  arises 
whether  the  distinctive  reactions  corresponding  to  the  separate 
taste  qualities  can  be  referred  to  a  definite  chemical  structure  in  the 
sapid  bodies.  Are  there  certain  chemical  groups  which  possess  the 
property  of  reacting  specifically  with  the  end-organs?  Experience 
shows  that  substances  of  very  different  chemical  constitution  may 


SENSATIONS  OF  TASTE  AND  SMELL.  299 

excite  the  same  taste.  Thus,  sugar,  saccharin,  and  sugar  of  lead 
(lead  acetate)  all  give  a  sweet  taste,  while,  on  the  other  hand, 
starch  (soluble  starch),  which  stands  so  close  in  structure  to  the 
sugars,  has  no  effect  upon  the  taste  terminals.  It  is  interesting 
to  remember  that  the  taste  nerves  may  be  stimulated  by  sapid  sub- 
stances dissolved  in  the  blood  as  well  as  when  applied  to  the  ex- 
terior of  the  tongue.  A  sweet  taste  may  be  experienced  in  diabetes 
from  the  sugar  in  the  blood,  or  a  bitter  taste  in  jaundice  from  the 
bile. 

The  Threshold  Stimulus. — The  determination  of  the  threshold 
stimulus  for  different  sapid  substances  is  made  by  ascertaining  the 
minimal  concentration  of  the  solution  which  is  capable  of  arousing 
a  taste  sensation.  The  delicacy  of  the  sense  of  taste  is  influenced, 
however,  by  certain  accessory  conditions  which  must  be  taken  into 
account.  Thus,  the  temperature  of  the  solution  is  an  important 
condition.  Very  cold  or  very  hot  solutions  do  not  react, — that  is, 
the  extremes  of  temperature  seem  to  diminish  or  destroy  the  sensi- 
tiveness of  the  end-organ.  A  temperature  between  10°  and  30°  C. 
gives  the  optimum  reaction.  So  also  the  delicacy  of  the  sense  of 
taste  is  increased  by  rubbing  the  sapid  solution  against  the  tongue. 
Doubtless  this  mechanical  action  facilitates  the  penetration  of  the 
sapid  body  into  the  mucous  membrane,  but  it  seems  also  to  in- 
crease the  irritability  of  the  end-organ.  It  is  our  habit  in  tasting 
bodies  with  the  tongue  to  rub  this  organ  against  the  hard  palate. 
With  regard  to  the  threshold  stimulus  such  results  as  the  following 
are  reported: 

Salty  (sodium  chlorid).  0.25    gm.   in    100  c.c.  H2O — detectible    on    tip    of 

tongue. 
Sweet  (sugar) 0.50  "  "  detectible  on  tip  of 

tongue. 
Acid  (HC1) 0.007  "  "  "  detectible  on  border  of 

tongue. 
Bitter  (quinin) 0.00005  "  "  "  "  detectible  on  root  of 

tongue. 

The  very  great  sensitiveness  of  the  tongue  to  bitter  substances  is 
evident  from  this  table. 

The  Olfactory  Organ. — The  end-organ  for  the  olfactory  sense 
lies  in  the  upper  part  of  the  nose,  and  consists  of  elongated,  epithe- 
lial-like  cells,  each  of  which  bears  on  its  free  end  a  tuft  of  six  to 
eight  hair-like  processes,  while  at  its  basal  end  it  is  continued  into 
a  nerve  fiber  that  passes  through  the  cribriform  plate  of  the  ethmoid 
bone  and  ends  in  the  olfactory  bulb.  These  olfactory  sense  cells 
lie  among  supporting  epithelial  cells  of  a  columnar  shape  (Fig. 
122).  At  the  free  edge  of  the  cells  there  is  a  limiting  membrane 
through  which  the  olfactory  hairs  project.  The  olfactory  sense 


300 


THE    SPECIAL   SENSES. 


cells  are  essentially  nerve  cells,  and  in  this  respect  resemble  the 
sense  cells  in  the  retina,  the  rods  and  cones,  rather  than  those  of  the 
ear  or  of  the  organs  of  taste.  The  distribution  of  the  olfactory 
cells,  according  to  v.  Brunn,  is  confined  to  the  nasal  septum  and  a 
portion  of  the  upper  turbinate  bone.  The  area  covered  in  each  nos- 
tril corresponds  to  about  250  square  millimeters.  The  epithelium 
of  the  lower  and  middle  turbinates  and  the  floor  of  the  nostrils  is 
composed  of  the  usual  ciliated  cells  found  in  the  respiratory  passages, 
while  the  so-called  vestibular  region  of  the  nose,  the  part  roofed  in 

by  the  cartilage,  is  covered 
by  a  stratified  pavement 
epithelium  corresponding  in 
structure  with  that  of  the 
skin.  These  latter  portions 
of  the  nose  are  supplied 
with  sensory  fibers  derived 
from  the  fifth  or  trigeminal 
nerve.  We  must  consider 
the  500  sq.  mm.  of  olfac- 
tory epithelium  as  the 
olfactory  sense  organ  com- 
parable physiologically  and 
perhaps  anatomically  to  the 
rod  and  cone  layer  of  the 
retina.  The  connections  of 
these  cells  with  the  central 
nervous  system  have  al- 
ready been  described  (p. 
217).  It  will  be  remem- 
bered that  the  fine,  non- 
medullated  fibers  springing 
from  the  basal  end  of  the 
sense  cells  enter  the  olfac- 
tory bulb  and  end  in  ter- 
minal arborizations  in  the  olfactory  glomeruli,  where  they  make  con- 
nections by  contact  with  the  dendrites  of  the  mitral  cells  of  the 
bulb.  Through  the  axons  of  these  mitral  cells  the  impulses  are  con- 
ducted along  the  olfactory  tract  to  their  various  terminations  in  the 
olfactory  lobe  itself,  either  of  the  same  or  of  the  opposite  side,  and 
eventually  also  in  the  cortical  region,  the  uncinate  gyrus  of  the 
hippocampal  lobe.  As  regards  the  olfactory  sense  cells,  the  nerve 
cells  in  the  olfactory  bulb  might  be  compared  with  the  nerve  gan- 
glion layer  of  the  retina,  and  the  nerve  fibers  of  the  olfactory  tract 
with  the  fibers  of  the  optic  nerve. 

The   Mechanism    of    Smelling. — Odoriferous    substances    to 


Fig.  122. — Cells  of  the  olfactory  region  (after 
v.  Brunn):  a,  a,  Olfactory  cells;  6,  6,  epithelial 
cells;  n,  n,  central  process  prolonged  as  an  olfac- 
tory nerve  fibril;  I,  Z,  nucleus;  c,  knob-like  clear 
termination  of  peripheral  process;  h,  h,  bunch  of 
olfactory  hairs. 


.SENSATIONS    OF   TASTE    AND    SMELL.  3Q1 

affect  the  olfactory  cells  must,  of  course,  penetrate  into  the  upper 
part  of  the  nasal  chamber.  This  end  is  attained  during  inspiration, 
either  by  simple  diffusion  or  by  currents  produced  by  the  act  of 
sniffing.  It  may  also  happen  by  way  of  the  posterior  nares.  In 
fact,  the  flavors  of  many  foods,  fruits,  wine,  etc.,  are  olfactory  rather 
than  gustatory  sensations.  When  such  food  is  swallowed  the  poste- 
rior nares  are  shut  off  from  the  pharynx  by  the  soft  palate,  but  in 
the  expiration  succeeding  the  swallow  the  odor  of  the  food  is  con- 
veyed to  the  olfactory  end-organ.  Flavors  are  perceived,  therefore, 
not  during  the  act  of  swallowing,  but  subsequently,  and  if  the  nostrils 
are  blocked,  as  in  coryza,  foods  lose  much  of  their  flavor.  Simply 
holding  the  nose  will  destroy  much  of  the  so-called  taste  of  fruits 
or  the  bouquet  of  wines.* 

Nature  of  the  Olfactory  Stimulus. — The  fact  that  smells  are 
transmitted  through  space  like  light  and  sound  has  suggested  the 
possibility  that  they  may  depend  upon  a  vibratory  movement  of 
some  medium.  This  view,  although  occasionally  defended  in 
modern  times,  is  apparently  entirely  incompatible  with  the  facts. 
The  usual  view  is  that  odoriferous  bodies  emit  particles  which,  as 
a  rule  at  least,  are  in  gaseous  form.  These  particles  are  con- 
veyed to  the  olfactory  epithelium  by  currents  in  the  air  or  by 
simple  gaseous  diffusion,  and  after  solution  in  the  moisture  of 
the  membrane  act  chemically  upon  the  sensitive  hairs  of  the  sense 
cells.  All  vapors  or  gases  are,  however,  not  capable  of  acting  as 
stimuli  to  these  cells;  so  that  evidently  the  odoriferous  character 
depends  upon  some  peculiarity  of  structure.  It  is  assumed  that 
there  are  certain  groups,  "odoriphore  groups,"  which  are  character- 
istic of  all  odoriferous  substances  and  by  virtue  of  which  these 
substances  react  with  the  special  form  of  protoplasm  found  in 
the  hair  cells.  Haycraftf  has  formulated  certain  fundamental 
conceptions  bearing  upon  the  relation  between  chemical  structure 
and  odoriferous  stimulation.  He  has  shown  that  the  power  to 
cause  smell,  like  other  physical  properties,  is  a  periodic  function  of 
the  atomic  weight — that  in  the  periodic  system,  according  to  Men- 
delejeff,  the  elements  in  certain  groups  are  characterized  by  their 
odoriferous  properties;  for  instance,  the  second,  fourth,  and  sixth 
members — sulphur,  selenium,  and  tellurium — of  the  sixth  group. 
Moreover,  in  organic  compounds  belonging  to  an  homologous  series 
the  smell  gradually  changes  and,  indeed,  increases  in  the  higher 
members  of  the  series, — that  is,  in  those  having  a  more  complex 
molecular  structure. 

The  Qualities  of  the  Olfactory  Sensations. — While  we  dis- 

*  For  many  interesting  facts  concerning  smelling  and  the  literature  to 
1895  see  Zwaardemaker,  "Die  Physiologic  des  Ge«*chs,"  Leipzig,  1895. 
fHaycraft,  "Brain,"  1888,  p.  166. 


302  THE  SPECIAL  SENSES. 

tinguish  a  great  many  different  kinds  of  odors,  it  has  been  found 
difficult,  indeed  impossible,  to  classify  them  very  satisfactorily 
into  groups.  That  is,  it  is  not  possible  to  pick  out  what  might  be 
called  the  fundamental  odor  sensations.  This  sense  was  doubtless 
used  by  primitive  man  chiefly  in  detecting  and  testing  food,  in  protect- 
ing himself  from  noxious  surroundings,  and  perhaps  also  in  controll- 
ing his  social  relations.  The  olfactory  sensations,  in  accordance  with 
this  use,  and  with  the  fact,  revealed  by  comparative  anatomy, 
that  this  sense  is  the  oldest  phylogenetically,  give  either  pleasant 
or  unpleasant  sensations  in  a  more  marked  and  universal  way  than 
in  the  case  of  vision  or  hearing,  approaching,  in  this  respect,  rather 
the  purely  sensual  characteristics  of  the  lower  senses,  the  bodily 
appetites.  Mankind  has  been  content  to  classify  odors  as  agree- 
able and  disagreeable,  and  to  designate  the  many  different  quali- 
ties of  odors  by  the  names  of  the  substances  which  in  his  individual 
experience  usually  give  rise  to  them.  A  number  of  observers  have 
proposed  classifications  more  or  less  complete  in  character.  One 
of  the  latest,  and  perhaps  the  best,  is  that  suggested  by  Zwaarde- 
maker  on  the  basis  of  the  nomenclatures  introduced  by  previous 
observers.  Adopting  first  the  general  grouping  into  pure  odors, 
odors  mixed  with  sensations  of  common  sensibility  from  the  mucous 
membrane  of  the  nose,  and  odors  mixed  or  confused  with  tastes,  he 
separates  the  pure  odors  or  odors  proper  into  nine  classes,  as  follows : 

I.  Odores  setherei  or  ethereal  odors,  such  as  are  given  by  the  fruits,  which 

depend  upon  the  presence  of  ethereal  substances  or  esters. 
II.  Odores  aromatic!  or  aromatic  odors,  which  are  typified  by  camphor 
and  citron,  bitter  almond  and  the  resinous  bodies.     This  class  is 
divided  into  five  subgroups. 

III.  Odores  fragrantes,  the  fragrant  or  balsamic  odors,  comprising  the  vari" 

ous  flower  odors  or  perfumes.     The  class  falls  into  three  subgroups. 

IV.  Odores  ambrosiaci,  the  ambrosial  odors,  typified  by  amber  and  musk. 

This  odor  is  present  in  the  flesh,  blood,  or  excrement  of  some  ani- 
mals, being  referable  in  the  last  instance  to  the  bile. 

V.  Odores  alliacei  or  garlic  odors,  such  as  are  found  in  the  onion,  garlic, 
sulphur,  selenium  and  tellurium  compounds.  They  fall  into  three 
subgroups. 

VI.  Odores  empyreumatici  or  the  burning  odors,  the  odors  given  by  roasted 
coffee,  baked  bread,  tobacco  smoke,  etc.    The  odors  of  benzol,  phenol, 
and  the  products  of  dry  distillation  of  wood  come  into  this  class. 
VII.  Odores  hircini  or  goat  odors.     The  odor  of  this  animal  arises  from  the 
caproic  and  caprylic   acid  contained  in  the  sweat;  cheese,  sweat, 
spermatic  and  vaginal  secretions  give  odors  of  a  similar  quality. 
VIII.  Odores  tetri  or  repulsive  odors,  such  as  are  given  by  many  of  the  nar- 
cotic plants  and  acanthus. 

IX.  Odores  nauseosi  or  nauseating  or  fetid  odors,  such  as  are  given  by  feces 
and  certain  plants  and  the  products  of  putrefaction. 

While  the  classification  serves  to  emphasize  a  number  of  marked 
resemblances  or  relations  that  exist  among  the  odors,  it  does  not 
rest  wholly  upon  a  subjective  kinship, — that  is,  the  different  odors 
brought  together  in  one  class  do  not  in  all  cases  arouse  in  us  sensa- 


SENSATIONS    OF   TASTE    AND    SMELL.  303 

tions  that  seem  to  be  of  related  quality.  It  is  not  impossible,  how- 
ever, that  further  analysis  may  succeed  in  showing  that  there  are 
certain  fundamental  qualities  in  our  numerous  odor  sensations. 
Our  position  regarding  the  odors  is  similar  to  that  which  formerly 
prevailed  in  the  case  of  the  taste  sensations.  It  was  thought  to  be 
impossible  to  classify  these  latter  satisfactorily  on  the  basis  of  a  few 
fundamental  sensations,  but  it  is  now  universally  accepted  that  all 
of  our  true  gustatory  sensations  show  one  or  more  of  four  primary 
taste  qualities.  As  was  said  above,  our  odor  sensations  are  classi- 
fied in  ordinary  life  as  agreeable  or  disagreeable,  and,  indeed, 
Haller,  the  great  physiologist  of  the  eighteenth  century,  divided 
odors  along  this  line  into  three  classes:  (1)  the  agreeable  or  am- 
brosial, (2)  the  disagreeable  or  fetid,  and  (3)  the  mixed  odors.  In 
many  cases,  no  doubt,  the  agreeableness  or  disagreeableness  of  an 
odor  depends  solely  upon  the  associations  connected  with  it.  If 
the  associative  memories  aroused  are  unpleasant  the  odor  is  dis- 
agreeable. Thus,  the  odor  of  musk,  so  pleasant  to  most  persons, 
produces  most  disagreeable  sensations  in  others,  on  account  of  past 
associations.  It  is  possible,  however,  that  there  is  some  funda- 
mental difference  in  physiological  reaction  between  such  odors  as 
those  of  putrefaction  and  of  a  violet  which  may  be  considered  as  the 
cause  of  the  difference  in  psychical  effect.  It  has  been  suggested,  for 
instance,  that  they  may  affect  the  circulation  in  the  brain  hi  opposite 
ways,  one  producing  an  increased,  the  other  a  decreased  flow. 
This  improbable  supposition  has  been  shown  to  be  devoid  of  foun- 
dation by  the  observations  of  Shiel  ds.*  In  his  experiments  the  vascu- 
lar supply  to  the  skin  of  the  arm  was  determined  by  plethysmo- 
graphic  methods,  and  it  was  found  that  both  pleasant  (heliotrope 
perfume)  and  unpleasant  (putrefactive)  odors  give  a  similar  vascu- 
lar reaction.  Each  class,  if  it  acts  at  all,  causes,  as  a  rule,  a  con- 
striction of  the  skin  vessels,  such  as  is  obtained  normally  from  in- 
creased mental  activity, — a  reaction  usually  interpreted  to  mean  a 
greater  flow  of  blood  to  the  brain. 

Fatigue  of  the  Olfactory  Apparatus. — It  is  a  matter  of 
common  observation  that  many  odors,  such  as  the  perfumes  of 
flowers,  quickly  cease  to  give  a  noticeable  sensation  when  the  stimu- 
lation is  continued.  This  result  is  usually  attributed  to  fatigue 
of  the  sense  cells  in  the  end-organ  and  it  is  noticeable  chiefly  with 
faint  odors.  One  who  sits  in  an  ill-ventilated  room  occupied  by 
many  persons  may  be  quite  unconscious  of  the  unpleasant  odor 
from  the  vitiated  air,  while  to  a  newcomer  it  is  most  distinct. 

Threshold  Stimulus — Delicacy  of  the  Olfactory  Sense. — 
The  extraordinary  delicacy  of  the  sense  of  smell  in  some  of  the  lower 
animals  is  seemingly  beyond  the  power  of  objective  measurement  or 
*  Shields,  "  Journal  of  Experimental  Medicine,"  1,  1896. 


304 


THE  SPECIAL  SENSES. 


expression.  The  ability  of  a  dog,  for  instance,  to  follow  the  trail  of 
a  given  person  depends  undoubtedly  upon  the  recognition  of  the 
individual  odor,  and  the  actual  amount  of  olfactory  material  left 
upon  the  ground  which  serves  as  the  stimulus  must  be  infinitesi- 
mally  small.  Even  in  ourselves  the  actual  amount  of  olfactory 
material  which  suffices  to  give  a  distinct  sensation  is  often  beyond 
our  means  of  determination  except  by  the  aid  of  calculation.  It 
is  recognized  in  chemical  work,  for  instance,  that  traces  of  known 
substances  too  small  to  give  the  ordinary  chemical  reactions  may  be 
detected  easily  by  the  sense  of  smell.  By  taking  known  amounts 


Fig.  123.-— Zwaardemaker's  olfactometer. 

of  odoriferous  substances  and  diluting  them  to  known  extents  it  is 
possible  to  express  in  weights  the  minimal  amount  of  each  substance 
that  can  cause  a  sensation.  By  this  method  such  figures  as  the 
following  are  obtained :  Camphor  is  perceived  in  a  dilution  of  1  part 
to  400 ,000;  musk,  1  part  to  8,000,000;  vanillin,  1  part  to  10,000,000; 
while,  according  to  the  experiments  of  Fischer  and  Penzoldt, 
mercaptan  may  be  detected  in  a  dilution  of  -j^  inrV  UIFTF  °f  a  mun" 
gram  in  1  liter  of  air  or  j^rirlnFTroT  °f  a  milligram  in  50  c.c.  of  air. 
Various  methods  have  been  proposed  to  determine  the  relative 
delicacy  of  the  olfactory  sense  in  different  persons,  and  these  methods 
have  some  application  in  the  clinical  diagnosis  of  certain  cases. 
Zwaardemaker  has  devised  a  simple  apparatus,  the  olfactometer, 
the  principle  of  which  is  illustrated  in  Fig.  123.  It  consists  of  an 
outside  cylinder — the  olfactory  cylinder,  whose  inner  surface  is  of 
porous  material  which  can  be  filled  with  a  known  strength  of  olfac- 
tory solution — and  an  inside  tube,  smelling  tube.  This  latter  is. 
applied  to  the  nose  and  where  it  runs  inside  the  cylinder  it  is  gradu- 


SENSATIONS  OF  TASTE  AND  SMELL.  305 

ated  in  centimeters.  It  is  evident  that  the  further  out  the  inner 
tube  is  pulled  the  greater  will  be  the  amount  of  olfactory  substance 
which  will  be  exposed  to  the  incoming  air  of  an  inspiration. 

Conflict  of  Olfactory  Sensations. — When  different  odors  are 
inhaled  simultaneously  through  the  two  nostrils  they  may  give  rise 
to  the  phenomenon  of  a  conflict  of  the  olfactory  fields  similar  to  that 
described  for  the  visual  fields.  That  is,  we  perceive  first  one  then 
the  other  without  obtaining  a  fused  or  compound  sensation.  The 
result  depends  largely  on  the  odors  selected.  In  some  cases  one 
odor  may  predominate  in  consciousness  to  the  entire  suppression 
of  the  other, — a  phenomenon  which  also  has  an  analogy  in  binocular 
sensations.  It  is  well  known,  also,  that  certain  odors  antagonize  or 
neutralize  others.  It  is  said,  for  instance,  that  the  odor  of  iodoform, 
usually  so  persistent  and  so  disagreeable,  may  be  neutralized  by  the 
addition  of  Peru  balsam,  and  that  the  odor  of  carbolic  acid  may 
destroy  that  of  putrefactive  processes.  Whether  the  neutralization 
is  of  a  chemical  nature  or  is  physiological  does  not  seem  to  have 
been  definitely  ascertained. 

Olfactory  Associations. — Personal  experience  shows  clearly 
that  olfactory  sensations  arouse  numerous  associations — our 
olfactory  memories  are  good.  On  the  anatomical  side  the  cortical 
center  in  the  hippocampal  lobe  is  known  to  be  widely  connected 
with  other  parts  of  the  cerebrum,  and  we  have  in  this  fact  a  basis  for 
the  extensive  associations  connected  with  odors.  In  animals  like 
the  dog,  with  highly  developed  olfactory  organs,  it  is  evident  that 
this  sense  must  play  a  correspondingly  large  part  in  the  psychical 
life.  In  such  animals  as  well  as  among  the  invertebrates  it  is  in- 
timately connected  with  the  sexual  reflexes,  and  some  remnant  of 
this  relationship  is  obvious  among  human  beings.  Among  the  so- 
called  special  senses  that  of  smell  is  perhaps  the  one  most  closely 
connected  with  the  bodily  appetites,  and  overgratification  or  over- 
indulgence of  this  sense,  according  to  historical  evidence,  has  at  least 
been  associated  with  periods  of  marked  decadence  of  virtue  among 
civilized  nations. 
20 


PHYSIOLOGY  OF  THE  EYE. 

The  eye  is  the  peripheral  organ  of  vision.  By  means  of  its 
peculiar  physical  structure  rays  of  light  from  external  objects  are 
focused  upon  the  retina  and  there  set  up  nerve  impulses  that  are 
transmitted  by  the  fibers  of  the  optic  nerve  and  optic  tract  to  the 
visual  center  in  the  cortex  of  the  brain.  In  this  last  organ  is 
aroused  that  reaction  in  consciousness  which  we  designate  as  a 
visual  sensation.  In  studying  the  physiology  of  vision  we  may 
consider  the  eye,  first,  as  an  optical  instrument  physically  adapted 
to  form  an  image  on  the  retina  and  provided  with  certain  physi- 
ological mechanisms  for  its  regulation;  secondly,  we  may  study 
the  properties  of  the  retina  in  relation  to  its  reactions  to  light, 
and  lastly,  the  visual  sensations  themselves,  or  the  physiology 
of  the  visual  center  in  the  brain. 


CHAPTER  XVII. 

THE  EYE  AS  AN  OPTICAL  INSTRUMENT— DIOPTRICS 
OF  THE  EYE. 

Formation  of  an  Image  by  a  Biconvex  Lens. — That  the  re- 
fractive surfaces  of  the  eye  form  an  image  of  external  objects  upon 
the  retinal  surface  is  a  necessary  conclusion  from  its  physical  struc- 
ture. The  fact  may  be  demonstrated  directly,  however,  by  ob-. 
servation  upon  the  excised  eye  of  an  albino  rabbit.  The  thin  coats 
of  such  an  eye  are  semitransparent,  and  if  the  eye  is  placed  in  a  tube 
of  blackened  paper  and  held  in  front  of  one's  own  eyes  it  can  be  seen 
readily  that  a  small,  inverted  image  of  external  objects  is  formed 
upon  the  retinal  surface,  just  as  an  inverted  image  of  the  exterior  is 
formed  upon  the  ground  glass  plate  of  a  photographic  camera.  This 
image  is  formed  in  the  eye  by  virtue  of  the  refractive  surfaces  of  the 
cornea  and  the  lens.  The  curved  surfaces  of  these  transparent  bodies 
act  substantially  like  a  convex  glass  lens,  and  the  physics  of  the 
formation  of  an  image  by  such  a  lens  may  be  used  to  explain  the 
refractive  processes  in  the  eye.  To  understand  the  formation 
of  an  image  by  a  biconvex  lens  the  following  physical  facts  must  be 

306 


DIOPTRICS  OF  THE  EYE. 


307 


borne  in  mind.  Parallel  rays  of  light  falling  upon  one  surface  of  the 
lens  are  brought  to  a  point  or  focus  (F)  behind  the  other  surface 
(Fig.  124).  This  focus  for  parallel  rays  is  the  principal  jocus  and 
the  distance  of  this  point  from  the  lens  is  the  principal  focal  dis- 
tance. This  distance  depends  upon  the  curvature  of  the  lens  and 
its  refractive  power,  as  measured  by  the  refractive  index  of  the 
material  of  which  it  is  composed.  Parallel  rays  are  given  theo- 
retically by  a  source  of  light  at  an  infinite  distance  in  front  of  the 
lens,  but  practically  objects  not  nearer  than  about  twenty  feet 
give  rays  so  little  divergent  that  they  may  be  considered  as  par- 


Fig.  124. — Diagrams  to  illustrate  the  refraction  of  light  by  a  convex  lens  :  a.,  Refrac- 
tion of  parallel  rays  ;  b.,  refraction  of  divergent  rays  ;  c.,  refraction  of  divergent  rays  from 
a  luminous  point  nearer  than  the  principal  focal  distance. 

allel,  so  far  as  the  optical  apparatus  of  the  eye  is  concerned.  On 
the  other  hand,  if  a  luminous  object  is  placed  at  F  the  rays  from 
it  that  strike  upon  the  lens  will  emerge  from  the  other  surface 
as  parallel  rays  of  light.  If  a  luminous  point  (/,  Fig.  124)  is 
placed  in  front  of  such  a  lens  at  a  distance  greater  than  the  prin- 
cipal focal  distance,  but  not  so  far  as  to  give  practically  parallel 
rays,  the  cone  of  diverging  rays  from  it  that  impinges  upon  the 
surface  of  the  lens  will  be  brought  to  a  focus  (/')  further  away 
than  the  principal  focus.  Conversely,  the  rays  from  a  lumin- 
ous point  at  /'  will  be  brought  to  a  focus  at  /.  These  points, 
/  and  /',  are,  therefore,  spoken  of  as  conjugate  foci.  All  luminous 


308 


THE   SPECIAL  SENSES. 


points  within  the  limits  specified  will  have  their  corresponding 
conjugate  foci,  at  which  their  images  will  be  formed  by  the  lens. 
Lastly,  if  a  luminous  point  is  placed  at  v,  Fig.  124,  nearer  to  the 
lens  than  the  principal  focal  distance,  the  cone  of  strongly  di- 
vergent rays  that  falls  upon  the  lens,  although  refracted,  is  still 
divergent  after  leaving  the  lens  on  the  other  side  and  consequently 
is  not  focused  and  forms  no  real  image  of  the  point.  For  every  lens 
there  is  a  point  known  as  the  optical  center,  and  for  biconvex  lenses 
this  point  lies  within  the  lens,  o.  The  line  joining  this  center  and 
the  principal  focus  is  the  principal  axis  of  the  lens  (o-F,  Fig.  124) . 
All  other  straight  lines  passing  through  the  optical  center  are  known 
as  secondary  axes.  Rays  of  light  that  are  coincident  with  any  of  these 
secondary  axes  suffer  no  angular  deviation  in  passing  through  the 
lens;  they  emerge  parallel  to  their  line  of  entrance  and  practically 
unchanged  in  direction.  Moreover,  any  luminous  point  not  on  the 


Fig.  125._ — Diagrams  to  illustrate  the  formation  of  an  image  by  a  biconvex  lens:    a,  For* 
mation  of  the  image  of  a  point ;   6,  formation  of  the  images  of  a  series  of  points. 


principal  axis  will  have  its  image  (conjugate  focus)  formed  some- 
where upon  the  secondary  axis  drawn  from  this  point  through  the 
optical  center.  The  exact  position  of  the  image  of  such  a  point 
can  be  determined  by  the  following  construction  (Fig.  125) :  Let  A 
represent  the  luminous  point  in  question.  It  will  throw  a  cone  of 
rays  upon  the  lens,  the  limiting  rays  of  which  may  be  represented  by 
A-b  and  A-c.  One  of  these  rays,  A-p,  will  be  parallel  to  the  prin- 
cipal axis,  and  will  therefore  pass  through  the  principal  focus,  F. 
If  this  distance  is  determined  and  is  indicated  properly  in  the 
construction,  the  line  A-p  may  be  drawn,  as  indicated,  so  as  to 
pass  through  F  after  leaving  the  lens.  The  point  at  wnich  the 
prolongation  of  this  line  cuts  the  secondary  axis,  A-o,  marks  the 


DIOPTRICS  OF  THE  EYE.  309 

conjugate  focus  of  A  and  gives  the  position  at  which  all  of  the 
rays  will  be  focused  to  form  the  image,  a.  In  calculating  the 
position  of  the  image  of  any  object  in  front  of  the  lens  the  same 
method  may  be  followed,  the  construction  being  drawn  to  de- 
termine the  images  for  two  or  more  limiting  points,  as  shown 
in  Fig.  125.  Let  A-B  be  an  arrow  in  front  of  the  lens.  The  image 
of  A  will  be  formed  at  a  on  the  secondary  axis  A-o,  and  the  image  of 
B  at  b  along  the  secondary  axis  B-o.  The  images  of  the  intervening 
points  will,  of  course,  lie  between  a  and  b;  so  that  the  image  of  the 
entire  object  will  be  that  of  an  inverted  arrow.  This  image  may  be 
caught  on  a  screen  at  the  distance  indicated  by  the  construction  if 
the  latter  is  drawn  to  scale.  The  principal  focus  of  a  convex  lens 
may  be  determined  experimentally  or  it  may  be  calculated  from  the 
formula  ~  +  ^  =  ~,  in  which  /  represents  the  principal  focal  dis- 
tance and  p  and  p1,  the  conjugate  foci  for  an  object  farther  away 
than  the  principal  focal  distance.  That  is,  if  the  distance  of  the 
object  from  the  lens,  p,  is  known,  and  the  distance  of  its  image,  p1, 
is  determined  experimentally,  the  principal  focal  distance  of  the 
lens,  /,  may  be  determined  by  the  formula.  The  principal  focus 

of  a  lens  may  be  calculated  also  from  the  radius  of  curvature, 

-p 
according  to  the  formula,  F  =      _  ..,  in  which F  ==  the  principal 

focus,  R  =  the  radius,  and  n  =  the  refractive  index  of  the  material. 
Since  in  glass,  n  =  approximately  1.5,  the  formula  for  this  material 
works  out  F  =  2  R. 

Formation  of  an  Image  by  the  Eye. — As  stated  above,  the  re- 
fractive surfaces  of  the  eye  act  essentially  like  a  convex  lens.  As  a 
matter  of  fact,  these  refractive  surfaces  are  more  complex  than 
in  the  case  of  the  biconvex  lens.  In  the  latter  the  rays  of  light 
suffer  refraction  at  two  points  only.  Where  they  enter  the  lens 
they  pass  from  a  rarer  to  a  denser  medium  and  where  they  leave  the 
lens  they  pass  from  a  denser  to  a  rarer  medium.  At  these  two 
points,  therefore,  they  are  refracted.  In  the  eye  there  is  a  larger 
series  of  refractive  surfaces.  The  light  is  refracted  at  the  anterior 
surface  of  the  cornea,  where  it  passes  from  the  air  into  the  denser 
medium  of  the  cornea ;  at  the  anterior  surface  of  the  lens,  where  it 
again  enters  a  denser  medium;  and  at  the  posterior  surface  of  the 
lens,  where  it  enters  the  less  dense  vitreous  humor.  The  relative 
refractive  powers  of  these  different  media  have  been  determined 
and  are  expressed  in  terms  of  their  refractive  indices,  that  of  air 
being  taken  as  unity.* 

*  The  term  index  of  refraction  expresses  the  constant  ratio  between  the 
angles  of  incidence  and  of  refraction,  or  specifically  between  the  sine  of  the 

sine  i 
angle  of  incidence  and  the  sine  of  the  angle  of  refraction:  -      -   =  index  of 

refraction. 


310 


THE  SPECIAL  SENSES. 


Fig.  126. — Diagram  to  illustrate  the  surfaces 
in  the  eye  at  which  the  rays  of  light  are  chiefly 
refracted. 


Index  of  refraction  for  air =1 

Index  of  refraction  for  cornea  and  aqueous  hu- 
mor   =   1.3365 

Index  of  refraction  for  crystalline  lens =   1.4371 

Index  of  refraction  for  vitreous  humor =   1.3365 

The  three  points  at  which  the  light  is  refracted  are  indicated 
in  the  accompanying  schema  (Fig.  126).  The  refractive  surfaces 
of  the  eye  may  be  considered  as  being  composed  of  a  concavo-convex 
lens,  the  cornea  and  aqueous  humor,  and  a  biconvex  lens,  the 
crystalline  lens.  In  a  system  of  this  kind,  composed  of  several 
refractive  media,  it  has  been  shown  that  to  construct  geometrically 

the  path  of  the  rays  it  is 
necessary  to  know  six 
points ;  these  are  the  six  car- 
dinal points  or  optical  con- 
stants of  Gauss, — namely, 
the  anterior  and  the  poste- 
rior focal  distance,  the  two 
nodal  points,  and  the  two 
principal  points.  So  far 
as  the  eye  is  concerned,  it 
has  been  shown  that  the 
path  of  the  rays  of  light 

may  be  represented  with  sufficient  accuracy  by  employing  what  is 
known  as  the  reduced  schematic  eye  of  Listing,  in  which  the 
refraction  is  supposed  to  take  place  at  a  single  convex  surface 
separating  two  media,  the  air  on  one  side  and  the  humor  of  the  eye 
on  the  other,  the  latter  having  a  refractive  index  of  1.33  (see  Fig. 
127).  In  this  reduced  eye  the  position  of  the  ideal  refracting 
surface  c'  lies  in  the  aqueous  humor,  at  a  distance  of  2.1  mms.  from 
the  anterior  surface  of  the 
cornea,  and  the  position  of 
the  nodal  point  or  optical 
center — that  is,  the  center 
of  curvature  of  the  ideal 
refracting  surface,  lies  in 
the  crystalline  lens  at  n,  a 
distance  of  7.3  mms.  from 
the  anterior  surface  of  the 
cornea.  The  principal  fo- 
cal distance  foi  this  refract- 
ing surface  lies  at  a  dis- 
tance of  20.7  mms.,  which 
would  be  equivalent  to 
22.8  mms.  (20.7  +  2.1) 
from  the  actual  surface  of  the  cornea  and  15.5  mms.  (22.8  —  7.3) 
from  the  nodal  point.  In  the  eye  at  rest  this  principal  focal 


Fig.  127. — Diagram  to  illustrate  the  reduced 
or  schematic  eye  with  a  single  refracting  surface 
separating  two  media  of  different  densities:  c', 
the  ideal  refracting  surface  situated  2.1  mms. 
behind  the  anterior  surface  of  real  cornea;  n, 
the  nodal  point,  or  center  of  curvature  of  the 
surface  c',  and  15.5  mms.  in  front  of  retina. 
The  eyeball  is  supposed  to  be  filled  with  a  uni- 
form substance  having  a  refractive  index  of  1.33. 
equal  to  that  of  the  vitreous  humor. 


DIOPTRICS    OF    THE    EYE. 


311 


distance  coincides  with  the  retina,  since  the  refracting  surfaces 
in  the  normal  resting  eye  are  so  formed  that  parallel  rays  (rays 
from  distant  objects)  are  brought  to  a  focus  on  the  retina.  To 
show  the  formation  of  the  image  of  an  external  object  on  the  retina 
it  suffices,  therefore,  to  use  a  construction  such  as  is  represented  in 
Fig.  128.  Secondary  axes  are  drawn  from  the  limiting  points  of  the 
object — A  and  B — through  the  nodal  point.  Where  these  axes 
cut  the  retina  the  retinal  image  of  the  object  will  be  formed.  That 
is,  all  the  rays  of  light  proceeding  from  A  that  penetrate  the  eye  will 
be  focused  at  a,  and  all  proceeding  from  B  at  b.  The  image  on 
the  retina  will  therefore  be  inverted  and  will  be  smaller  than  the 
object.  The  angle  formed  at  the  nodal  point  by  the  lines  A-n  and 
B-n  is  known  as  the  visual  angle;  it  varies  inversely  with  the  dis- 
tance of  the  object  from  the  eye. 

The  Inversion  of  the  Image  on  the  Retina. — Although  the 
images  of  external  objects  on  the  retina  are  inverted,  we  see  them 
erect.  This  fact  is  easily  understood  when  we  remember  that  our 
actual  visual  sensations  take  place  in  the  brain  and  that  the  pro- 
jection of  these  sensations  to  the  exterior  is  a  secondary  act  that  has 
been  learned  from  experience.  Experience  has  taught  us  to  project 
the  visual  sensation  arising  from  the  stimulation  of  any  given  point 
on  the  retina  to  that  part 
of  the  external  world 
from  which  the  stimulus 
arises — that  is,  to  the 
luminous  point  giving 
origin  to  the  light  rays. 
According  to  the  physi- 
cal principles  described 
above,  the  image  of  such 
a  point  must  be  formed 
on  the  retina  where  the 
secondary  axis  from  that 

point  through  the  nodal  point  touches  the  retina.  In  projecting  this 
retinal  stimulus  outward  to  its  source,  therefore,  we  have  learned 
to  project  it  back,  as  it  were,  along  the  line  of  its  secondary  axis. 
In  Fig.  128  the  retinal  stimulus  at  a  is  projected  outward  along 
the  line  a-n-A,  and  to  such  a  distance  as,  from  other  sources,  we 
estimate  the  object  A  to  be.  This  law  of  projection  is  fixed  by 
experience,  but  it  implies,  as  will  be  noted,  that  we  are  conscious 
of  the  differences  in  sensation  aroused  by  stimulation  of  different 
parts  of  the  retina.  Considering  the  retina  as  a  sensory  surface, 
— like  the  skin,  for  instance, — each  point,  speaking  in  general  terms, 
may  be  assumed  to  be  connected  with  a  definite  portion  of  the 
cortex,  and  the  sensation  aroused  by  the  stimulation  of  these  dif- 
ferent points  must  differ  to  some  extent  in  consciousness,  each  has 


Fig.  128. — Diagram  to  illustrate  the  construc- 
tion necessary  to  determine  the  location  and  size  of 
the  retinal  image. 


312  THE  SPECIAL  SENSES. 

its  local  sign.  The  sensations  arising  from  each  of  these  points  we 
have  learned  to  project  outward  into  the  external  world  along  the 
line  from  it  to  the  nodal  point  of  the  eye,  because  under  the  normal 
conditions  of  life  this  point  is  stimulated  only  by  external  objects 
situated  on  this  line.  This  law  of  projection  is  so  firmly  fixed  that 
if  a  given  point  in  the  retina  is  stimulated  in  some  unusual  way 
we  still  project  the  resulting  sensation  outward  according  to  the 
law,  and  thus  make  a  false  projection  and  interpretation.  For 
instance,  if  the  little  finger  is  inserted  into  the  inner  and  lower  angle 
of  the  eye  and  is  pressed  upon  the  eyeball  the  edge  of  the  retina  is 
stimulated  mechanically.  One  experiences,  in  consequence,  a 
visual  sensation,  known  as  a  phosphene,  consisting  of  a  dark-blue 
spot  surrounded  by  a  light  halo.  This  sensation,  however,  is 
projected  out  toward  the  upper  and  outer  angle  of  the  eye,  accord- 
ing to  the  law  of  projection,  since  normally  this  part  of  the  retina 
is  only  stimulated  by  light  coming  from  such  a  direction.  A  similar 
error  in  projection  is  obtained  by  holding  objects  so  close  to  the  eye 
that  a  physical  inverted  image  cannot  be  formed,  but  only  an  erect 
shadow  image.  This  experiment  may  be  performed  as  follows: 
Hold  the  head  of  a  pin  close  to  the  eye,  and,  in  order  that  a  sharp 
shadow  may  be  thrown,  allow  the  light  to  fall  on  this  pin  through 
a  pinhole  in  a  card  held  somewhat  farther  from  the  eye.  By  this 
means  an  erect  shadow  of  the  pin,  lying  in  the  circle  of  light  from 
the  hole,  will  be  thrown  on  the  eye.  This  shadow  image  will  be 
projected  outward  according  to  the  usual  law,  and  consequently 
will  appear  inverted. 

The  Size  of  the  Retinal  Image. — The  size  of  the  image  of  an 
object  on  the  retina  may  be  reckoned  easily,  provided  the  size  of  the 
object  and  its  distance  from  the  eye  is  known.  As  will  be  seen  from 
the  construction  given  in  Fig.  128,  the  triangles  A-n-B  and  a-n-b  are 
symmetrical ;  consequently  we  have  the  ratio : 

A-B   :  a-b     :  :    A-n   :  a-n      or 

A-B          A-n      ,, 

— r-  =  ;  that  is 

a-b  a-n  ; 

Size  of  object          Distance  of  object  from  nodal  point. 
Size  of  image    *  *    Distance  of  image  from  nodal  point. 

As  was  stated  above,  the  distance  of  the  image  from  the  nodal 
point — that  is,  the  distance  of  the  retina  from  the  nodal  point — 
may  be  placed  at  15.5  or  15  mms.  Consequently,  three  of  the  factors 
in  the  above  equation  being  known,  it  is  easily  solved  for  the  un- 
known factor — namely,  the  size  of  the  image  on  the  retina.  To 
take  a  concrete  example;  suppose  it  is  desired  to  know  the  size  on 
the  retina  of  the  image  made  by  an  object  120  feet  high  at  a  distance 
of  one  mile  (5280  feet).  If  we  designate  the  size  of  the  image  as  x 
and  substitute  the  known  values  for  the  other  terms  of  the  equation. 


DIOPTRICS  OF  THE  EYE.  313 

we  have  —  =  -r-,  or  x  =  0.341  mm.,  which  is  about  the  diam- 


eter of  the  fovea  centralis.  The  retinal  image  of  the  object  in 
this  case  would  be,  in  round  numbers,  about  -nnrVinr  °f  the  actual 
height  of  the  object. 

Accommodation  of  the  Eye  for  Objects  at  Different  Dis- 
tances. —  The  normal  or,  as  it  is  sometimes  named,  the  emmetropic 
eye,  is  arranged  to  focus  parallel  rays  more  or  less  accurately  upon 
the  retina.  That  is,  the  refractive  media  have  such  curvatures  and 
densities  that  parallel,  or  substantially  parallel  rays  are  brought  to 
a  focus  upon  the  retinal  surface.  When  objects  are  brought  closer 
to  the  eye,  however,  the  rays  proceeding  from  them  become  more 
and  more  divergent.  If  the  eye  remains  unchanged  the  refracted 
rays  cut  the  retina  before'  coming  to  a  focus  —  so  that  each 
luminous  point  in  the  object,  instead  of  forming  a  point  upon  the 


Fig.  129. — Diagram  explaining  the  change  in  the  position  of  the  image  reflected  from  the 
anterior  surface  of  the  crystalline  lens. — (Williams,  after  Donders.) 

retina,  forms  a  circle,  known  as  a  diffusion  circle.  As  this 
is  true  for  each  point  of  the  object,  the  retinal  image  as  a  whole 
is  blurred.  We  know,  however,  that  up  to  a  certain  point 
at  least  this  blurring  does  not  occur  when  the  object  is  brought 
closer  to  the  eyes.  The  eye,  in  fact,  accommodates  itself  to  the 
nearer  object  so  as  to  obtain  a  clear  focus.  In  a  photographic 
camera  this  accommodation  or  focusing  is  effected  by  moving  the 
ground  glass  plate  farther  away  as  the  object  is  brought  closer  to  the 
lens.  In  the  eye  the  same  result  is  obtained  by  increasing  the  curva- 
ture and  therefore  the  refractive  power  of  the  lens.  That  a  change 
in  the  lens  is  the  essential  factor  in  accommodation  for  near  objects 
is  demonstrated  by  a  simple  and  conclusive  experiment  devised  by 


314  THE    SPECIAL    SENSES. 

Helmholtz  with  the  aid  of  what  are  known  as  the  images  of  Pur- 
kinje.  The  principle  of  this  experiment  is  represented  by  the  dia- 
gram given  in  Fig.  129.  The  eye  to  be  observed  is  relaxed; 
that  is,  gazes  into  the  distance.  A  lighted  candle  is  held  to  one 
side  as  represented,  and  the  observer  places  his  eye  so  as  to 
catch  the  light  of  the  candle  when  reflected  from  the  observed  eye. 
With  a  little  practice  and  under  the  right  conditions  of  illumina- 
tion the  observer  will  be  able  to  see  three  images  of  the  candle  re- 


Fig.  130. — Reflected  images  of  a  candle  flame  as  seen  in  the  pupil  of  an  eye  at  rest  and 
accommodated  for  near  objects. — (Williams.) 

fleeted  from  the  observed  eye  as  from  a  mirror:  one,  the  brightest, 
is  reflected  from  the  convex  surface  of  the  cornea  (a,  Fig.  130,  A) ; 
one  much  dimmer  and  of  larger  size  is  reflected  from  the  convex 
surface  of  the  lens  (b,  Fig.  130,  A).  This  image  is  larger  and 
fainter  because  the  reflecting  surface  is  less  curved.  The  third 
image  (c,  Fig.  130,  A)  is  inverted  and  is  smaller  and  brighter 
than  the  second.  This  image  is  reflected  from  the  posterior 
surface  of  the  lens,  which  acts,  in  this  instance,  like  a  concave 
mirror.  If  now  the  observed  eye  gazes  at  a  near  object,  it  will 
be  noted  (Fig.  130,  B)  that  the  first  image  does  not  change  at 
all,  the  third  image  also  remains  practically  the  same,  but  the 
middle  image  (b)  becomes  smaller  and  approaches  nearer  to  the 
first  (a).  This  result  can  only  mean  that  in  the  act  of  accom- 
modation the  anterior  surface  of  the  lens  becomes  more  convex. 
In  this  way  its  refractive  power  is  increased  and  the  more  diver- 
gent rays  from  the  near  object  are  focused  on  the  retina.  Helm- 
holtz has  shown  that  the  curvature  of  the  posterior  surface  of  the 
lens  is  also  increased  slightly;  but  the  change  is  so  slight  that  the 
increased  refractive  power  is  referred  chiefly  to  the  change  in  the 
anterior  surface.  The  means  by  which  the  change  is  effected 
was  first  explained  satisfactorily  by  Helmholtz.*  He  attributed 
it  to  the  contraction  of  the  ciliary  muscle.  This  small  muscle, 
composed  of  plain  muscle  fibers,  is  found  within  the  eyeball,  lying 
between  the  choroid  and  the  sclerotic  coat  at  the  point  at  which  the 
sclerotic  passes  into  the  cornea  and  the  choroid  falls  into  the  ciliary 
*  Helmholtz,  "Handbuch  der  physiologischen  Optik,"  second  edition,  1896. 


DIOPTRICS    OF   THE    EYE.  315 

processes.  Some  of  its  fibers  take  a  more  or  less  circular  direction 
around  the  eyeball,  resembling  thus  a  sphincter  muscle,  while  others 
take  a  radial  direction  in  the  planes  of  the  meridians  of  the  eye  and 
have  their  insertion  in  the  choroid  coat  (Fig:  131).  When  this 
muscle  contracts  the  radial  fibers  especially  will  pull  forward  the 
choroid  coat.  The  effect  of  this  change  in  the  choroid  is  to  loosen 
the  pull  of  the  suspensory  ligament  (zonula  Zinnii)  on  the  lens  and 
this  organ  then  bulges  forward  by  its  own  elasticity.  The  theory 
assumes  that  in  a  condition  of  rest  the  suspensory  ligament,  which 
runs  from  the  ciliary  processes  to  the  capsule  of  the  lens,  exerts  a 

Ciliary    Border 

process,  of  iris.          Ciliary  muscle. 


Pigment 
epithelium 


Ora  serrata. 

Fig.  131. — Meridional  section  of  eyeball  after  removal  of  sclerotic  coat,  cornea,  and  iris, 
to  show  the  position  of  the  ciliary  muscle. — (Schultze.) 

tension  upon  the  lens  which  keeps  it  flattened,  particularly  along 
its  anterior  surface,  since  the  ligament  is  attached  more  to  this  side. 
When  this  tension  is  relieved  indirectly  by  the  contraction  of  the 
ciliary  muscle  the  elasticity  of  the  lens,  or  rather  of  the  capsule  of 
the  lens,  causes  it  to  assume  a  more  spherical  shape  along  its  anterior 
surface,  and  the  amount  of  this  change  is  proportional  to  the 
extent  of  contraction  of  the  muscle.  Other  theories  have  been 
proposed  to  explain  the  way  in  which  the  contraction  of  the  ciliary 
muscle  effects  a  change  in  the  curvature  of  the  lens,*  but  none  is 
so  simple  and,  on  the  whole,  so  satisfactory  as  the  one  suggested 
by  Helmholtz. 

It  is  interesting  to  note  that  in  fishes  accommodation  is  effected  in  a 
different  way,  namely,  by  movements  of  the  lens  forward  and  backward. 
In  these  animals  the  eye  when  at  rest  is  accommodated  for  near  vision,  and 
to  see  objects  at  a  distance  the  refractive  power  of  the  eye  is  diminished  by 
the  contraction  of  a  special  muscle,  retractor  lentis,  which  pulls  the  lens  toward 
the  retina,  f 

*See  Tscherning,   "  Optique  physiologique,"  Paris,    1898;   and   Schoen, 
"  Archiv  f.  die  gesammte  Physiologic,"  59,  427,  1895. 

|See  Beer,  "Wiener  klihische  Wochenschrift, "  1898,  No.  12. 


316  THE  SPECIAL  SENSES. 

Limit  of  the  Power  of  Accommodation — Near  Point  of 
Distinct  Vision. — When  an  object  is  brought  closer  and  closer  to 
the  eye  a  point  will  be  reached  at  which  it  is  impossible  by  the 
strongest  contraction  of  the  ciliary  muscle  to  obtain  a  clear  image 
of  the  object.  The  rays  from  it  are  so  divergent  that  the  refractive 
surfaces  are  unable  to  bring  them  to  a  focus  on  the  retina.  Each 
luminous  point  makes  a  diffusion  circle  on  the  retina,  and  the 
whole  image  is  indistinct.  The  distance  at  which  the  eye  is  just 
able  to  accommodate  and  within  which  distinct  vision  is  impos- 
sible is  called  the  near  point.  Observation  shows  that  this  near 
point  varies  steadily  with  age  and  becomes  rapidly  greater  hi  dis- 
tance between  the  fortieth  and  the  fiftieth  year.  In  the  case  of  the 
normal  eye  the  recession  of  the  near  point  varies  so  regularly  with 
age  that  its  determination  may  be  used  to  estimate  the  age  of  the 
individual.  Figures  of  this  kind  are  given  (see  also  p.  318) : 


AGE. 
10   

NE 

7  CK 

AR  POINT. 
n.  or  2.76  in. 
3.94  " 
5.61  " 
8.66  " 
15.75  " 
39.37  " 

20   

10 

30   

14 

40  

22 

50  

40 

60.  . 

.  100 

This  gradual  lengthening  of  the  near  point  is  explained  usually 
by  the  supposition  that  the  lens  loses  its  elasticity,  so  that  con- 
traction of  the  ciliary  muscle  has  less  and  less  effect  in  causing  an 
increase  in  its  curvature.  The  process  starts  very  early  in  life, 
and  is  one  of  the  many  facts  which  show  that  senescence  begins 
practically  with  birth.  The  change  in  near  point  in  early  life  is  so 
slight  as  to  escape  notice,  but  after  it  reaches  a  distance  of  about 
25  cm.  (about  10  inches)  the  fact  obtrudes  itself  upon  us  hi  the  use 
of  our  eyes  for  near  objects, — reading,  for  example.  The  condition 
is  then  designated  as  old-sightedness  or  presbyopia.  Most  normal 
eyes  become  so  distinctly  presbyopic  between  the  fortieth  and  the 
fiftieth  year  as  to  require  the  use  of  glasses  hi  reading.  If  no  other 
defect  exists  in  the  eye,  this  deficiency  of  the  lens  is  readily  over- 
come by  using  suitable  convex  glasses  to  aid  the  eye  in  focusing 
the  rays.  It  is  obvious  that  in  such  cases  the  glasses  need  not  be 
used  except  for  near  work. 

Far  Point  of  Distinct  Vision. — The  normal  eye  is  so  adjusted 
that  parallel  rays  are  brought  to  a  focus  on  the  retina.  The  far 
point  is  therefore  theoretically  at  infinity.  Objects  at  a  great 
distance  are  seen  distinctly,  as  far  as  their  size  permits,  without 
accommodation, — that  is,  with  the  eye  at  rest.  Practically  it  is 
found  that  objects  at  a  distance  of  6  to  10  meters  (20  to  30  feet)  send 
rays  that  are  sufficiently  parallel  to  focus  on  the  retina  without 
muscular  effort  on  the  part  of  the  eyes,  and  this  distance,  therefore, 
measures  the  practical  far  point,  punctum  remotum,  of  the  normal 


DIOPTRICS    OF    THE    EYE.  317 

eye.  The  rays  at  this  distance  are,  in  reality,  somewhat  divergent, 
and  that  they  produce  a  distinct  image  without  an  act  of  accom- 
modation may  be  due  to  the  fact  that  the  rods  and  cones,  the  really 
sensitive  part  of  the  retina,  do  not  form  a  mathematical  plane,  but 
have  a  certain  thickness  or  depth.  In  the  fovea  centralis,  for  in- 
stance, the  cones  have  a  length  estimated  (Greeff)  at  85  //  (0.085 
mm.),  and  since  the  displacement  of  the  focus  of  an  object  moved 
from  an  infinite  distance  (parallel  rays)  to  6  or  10  meters  from  the 
eye  is  less  than  this  amount,  the  focused  image  would  continue  to 
fall  on  some  part  of  the  cones  without  the  aid  of  the  mechanism  of 
accommodation. 

The  Refractive  Power  of  the  Eye  and  the  Range  of  Accom- 
modation.— The  refractive  power  of  lenses  is  expressed  usually 
in  terms  of  their  principal  focal  distance.  A  lens  with  a  distance 
of  one  meter  is  taken  as  the  unit  and  is  designated  as  having  a 
refractive  power  of  one  diopter,  1  D.  Compared  with  this  unit, 
the  refractive  power  of  lenses  is  expressed  in  terms  of  the  recipro- 
cal of  their  principal  focal  distance  measured  in  meters;  thus, 
a  lens  with  a  principal  focal  distance  of  -^  meter  is  a  lens  of  10 
diopters,  10  D.,  and  one  with  a  focal  distance  of  10  meters  is 
^  diopter  (0.1  D.).  In  expressions  of  this  kind  it  is  assumed  that 
the  lens  is  surrounded  by  air  on  both  sides.  In  the  case  of  the  eye, 
in  which  there  is  air  on  one  side  and  liquid  (humor)  on  the  other, 
it  is  necessary  to  distinguish  between  an  anterior  and  a  posterior 
focal  distance,  according  as  the  rays  of  light  are  conceived  as 
passing  from  the  air  into  the  eye  and  forming  their  focus  in  the 
vitreous  humor  (posterior  principal  focus),  or  as  passing  in  the 
opposite  direction  and  forming  their  focus  in  the  air  (anterior 
principal  focus).  The  posterior  principal  focal  distance  (reduced 
eye)  may  be  given  as  20  +  mm.,  while  the  anterior  focal  distance 
is  equal  to  15  mm.  (13  mm.  in  front  of  cornea).  Compared  with  a 
glass  lens  in  air,  the  equivalent  refractive  power  of  the  eye  is  equal 
to  50  D  (^r),  reckoned  for  the  posterior  focal  distance,  or  66  D 
(TJT),  reckoned  for  the  anterior  focal  distance.  In  the  combined 
system  of  cornea  and  lens  the  action  of  the  cornea  is  more  im- 
portant than  that  of  the  lens.  Removal  of  the  lens,  as  in  cataract 
operations,  does  not  lessen  the  refractive  power  of  the  eye  so 
much  as  when  the  action  of  the  cornea  is  destroyed,  as  happens 
for  the  most  part  when  the  head  is  immersed  in  water.  The 
total  refractive  power  of  the  eye  is  increased  by  the  act  of  accom- 
modation, on  account  of  the  greater  curvature  of  the  lens.  As 
stated  in  a  preceding  paragraph,  the  extent  of  accommodation 
varies  with  age.  At  ten  years  the  range  is  from  infinity,  when  the 
eye  is  at  rest,  to  7ctm.  when  the  maximum  accommodation  is  used. 
In  other  words,  the  increased  curvature  of  the  front  of  the  crystal- 
line lens  in  maximal  accommodation  adds  to  the  refractive  power 


318 


THE    SPECIAL    SENSES. 


of  the  eye  an  amount  which  may  be  expressed  as  equivalent  to 


14  +  D  ( 


1000 


It  is  as  though  the  eye  were  left  at  rest  and  a 


glass  lens  of  14  +  D  were  placed  against  the  cornea.  The  de- 
creasing range  of  accommodation  as  age  increases  is  expressed 
conveniently  in  the  number  of  diopters  which  may  be  added  to  the 
refractive  power  of  the  eye  by  the  action  of  the  ciliary  muscle. 


8 

'7 
16 
'5 
H 
'3 

12 
11 
10 

9 
8 
7 
6 

12    16   20    24   28  32  36  40  44   48    52  56  £o  64  68  72 

N 

\ 

C\ 

\ 

X 

\ 

A^ 

\ 

N 

\ 

x 

\ 

\ 

N 

\ 

^ 

\ 

\ 

\ 

\ 

\ 

\ 

\ 

\ 

\ 

\ 

\ 

S 

\ 

\ 

5 
4 
3 

2 

1 

Fig.  131o.—  ( 
along  the  absciss 
dation:  C  C,  Rej 

\ 

\ 

\ 

\ 

\ 

\ 

\ 

\ 

\ 

N 

\ 
\ 

\ 
\ 

\ 

\ 
X, 

^^ 
•^-^ 

--  

•  
—  . 

~  .-= 

--     •• 

B 

Z 

Curves  showing  the  variation  in  the  range  of  accommodation  with  age.    Figures 
a  represent  years;  figures  along  the  ordinate  represent  diopters  of  accommo- 
iresents  the  mean  or  average  of  over  1000  cases,  while  A  A  and  B  B  gives  the 

extremes  noted  in  these  cases.  It  should  be  stated  that  the  maximum  accommodation  or  near 
point  was  reckoned  from  the  anterior  principal  focus  (13  mm.  in  front  of  the  cornea)  instead 
of  from  the  anterior  surface  of  the  cornea  (Duane) . 

The  following  table  illustrates  the  usual  range  of  accom- 
modation for  different  ages.  (Somewhat  different  results  are  ex- 
pressed in  the  curve*  represented  in  Fig.  13 la): 

Range  of  accommodation 

in  diopters. 

14 


Years. 
10 
15 
20 
25 
30 
35 
40 
45 
50 
55 
60 
65 
70 


12 

10 
8.5 
7 

5.5 
4.5 
3.5 
2.5 
1.75 
1 

0.75 
0.25 


*  Duane,  "  The  Ophthalmoscope,"  Sept.,  1912. 


DIOPTRICS    OF   THE    EYE  319 

Optical  Defects  of  the  Normal  Eye. — The  refractive  surfaces 
of  the  eye  exhibit  some  of  the  optical  defects  commonly  noticed 
in  lenses,  particularly  those  defects  known  as  chromatic  and  spherical 
aberration.  White  light  is  composed  of  ether  waves  of  different 
lengths  and  different  rapidities  of  vibration,  the  shortest  waves  being 
those  at  the  violet  end  of  the  spectrum  and  the  longest  those  at  the 
red  end.  In  passing  through  a  prism  or  lens  these  waves  are  re- 
fracted unequally  and  are  therefore  more  or  less  dispersed  accord- 
ing to  the  character  of  the  refracting  medium.  The  short,  rapid 
waves  at  the  violet  end  are  refracted  the  most  and  are  brought  to 
a  focus  before  the  longer,  red  waves,  so  that  the  image  shows 
fringes  of  color  instead  of  being  pure  white.  This  phenomenon 
is  known  as  chromatic  aberration.  Lenses  used  for  scientific 
purposes  are  corrected  for  this  defect  or  made  achromatic  by  a 
combination  of  lenses  of  crown  and  flint  glass  so  placed  that  the 
dispersive  power  of  one  neutralizes  that  of  the  other.  The  eye 
exhibits  this  defect,  but  not  to  such  an  extent  as  to  be  noticeablt 
in  ordinary  vision.  If,  however,  an  object  is  in  focus  when  viewed 
by  red  light  it  can  be  shown  that  the  focus  must  be  changed  if  the 
same  object  is  illuminated  by  violet  light.  Helmholtz  estimates 
that  if  the  media  of  the  eye  possess  the  same  dispersive  power  as 
water  the  rays  of  violet  light  must  be  brought  to  a  focus  at  about 
0.434  mm.  in  front  of  that  of  the  red  rays. 

Spherical  aberration  depends  upon  the  fact  that  the  rays  near  the 
circumference  of  a  lens  are  refracted  more  and  therefore  are  brought 
to  a  focus  sooner  than  those  entering  nearest  the  center.  This 
defect  may  be  noticed  in  an  unconnected  lens  by  the  fact  that 
when  the  center  of  the  image  is  hi  exact  focus  its  margins  are 
slightly  out  of  focus  and  vice  versa.  The  defect  is  usually  cor- 
rected, as  in  photography,  by  use  of  a  diaphragm  to  cut  off 
the  rays  from  the  periphery  of  the  lens.  In  the  eye  both  spher- 
ical and  chromatic  aberrations  are  remedied  to  a  large  extent  by 
a  similar  device.  The  iris  constitutes  an  adjustable  diaphragm, 
which  reflexly  narrows  as  the  light  increases  in  intensity  and 
thus  cuts  off  the  rays  that  would  go  through  the  periphery  of 
the  lens.  The  interesting  physiological  control  of  the  movements 
of  the  iris  is  described  below.  In  the  eye  the  defect  of  spherical 
aberration  is  counteracted  also  by  the  peculiar  structure  of  the 
crystalline  lens.  This  organ  is  composed  of  concentric  layers 
whose  density  increases  toward  the  center.  The  result  of  this 
arrangement  is  that  the  center  of  the  lens  is  more  refractive  than  the 
periphery,  and  the  tendency  of  the  latter  portion  to  refract  more 
strongly  is  more  or  less  neutralized. 

Abnormalities  in  the  Refraction  of  the  Eye — Ametropia.— 
The  eye  that  is  normal  and  in  which  parallel  rays  focus  on  the 
retina  when  the  eye  is  at  rest  is  designated  as  emmetropic.  Any 


320  THE  SPECIAL  SENSES. 

abnormality  in  the  refractive  surfaces  or  the  shape  of  the  eyeball 
prevents  this  exact  focusing  of  parallel  rays  and  makes  the  eye 
ametropic.  The  most  common  refractive  troubles  of  the  eye 
are  due  to  short-sightedness  or  myopia,  far-sightedness  or  hyper- 
metropia,  astigmatism,  and  old-sightedness  or  presbyopia.  Some 
description  of  these  conditions  is  useful  to  emphasize  by  contrast 
the  mode  of  action  of  the  dioptric  mechanism  in  the  normal  eye, 
but  for  a  full  description  of  the  extent  and  complexity  of  these 
defects  reference  must  be  made  to  special  treatises  upon  the 
errors  of  refraction  in  the  eye. 

In  myopia  or  near-sightedness  parallel  rays  of  light  are  brought 
to  a  focus  before  reaching  the  retina.  Consequently  when  the  rays 
fall  upon  the  retina  each  point  forms  a  diffusion  circle  and  the  image 
is  indistinct.  This  defect  may  be  due  to  an  abnormally  great  cur- 
vature of  the  refractive  surfaces,  the  cornea  or  the  lens,  or  to  an  ab- 
normal length  of  the  eyeball  in  its  anteroposterior  diameter.  The 
latter  cause  is  the  more  common.  The  defect  may  be  congenital, 
but  usually  it  is  acquired,  and  in  the  latter  case  its  cause  is  generally 
attributed  to  a  weakness  in  the  coats  of  the  eyeball.  The  interior 
of  the  eye  is  under  some  pressure,  intra-ocular  tension,  which  is 
estimated  to  be  equal  to  the  pressure  of  a  column  of  mercury  25  to  30 
mms.  in  height.  This  tension  is  increased  by  strong  convergence  of 
the  eyeballs  in  looking  at  near  objects.  If  the  coats  of  the  eye  are 
weak  or  become  so  from  disease  or  malnutrition  they  may  yield 
somewhat  to  this  pressure  and  the  eyeball  become  lengthened  in  the 
anteroposterior  diameter.  The  condition  as  regards  refraction  of 
parallel  rays  is  represented  then  by  the  diagram  B,  in  Fig.  132. 
The  retina  is  farther  away  than  the  principal  focal  distance  of  the 
refractive  surfaces,  and  if  the  defect  is  excessive  even  diverging 
rays  may  not  be  focused.  The  obvious  remedy  for  such  a  condition 
is  to  use  concave  lenses  before  the  eyes  for  distant  vision.  By  this 
means,  if  the  lenses  are  properly  chosen,  the  rays  will  be  given  such 
an  amount  of  divergence  that  the  focus  will  be  thrown  back  to  the. 
retina.  As  compared  with  the  normal  or  emmetropic  eye,  the 
myopic  eye  has  its  far  point  of  distinct  vision — that  is,  the  farthest 
point  that  can  be  seen  distinctly  without  an  effort  of  accommo- 
tion — less  than  twenty  feet  from  the  eye,  the  exact  distance  depend- 
ing upon  the  extent  of  the  myopia.  On  the  contrary,  the  near  point 
of  distinct  vision — that  is,  the  nearest  point  at  which  distinct  vision 
can  be  obtained  with  the  aid  of  the  muscles  of  accommodation — is 
closer  than  in  the  normal  eye.  Much  of  the  prevalent  myopia  in  the 
young  is  attributed  by  oculists  to  bad  methods  in  reading,  such  as 
insufficient  lighting,  small  print,  and  a  faulty  position  of  the  book. 
Such  conditions  lead  to  an  excessive  muscular  effort  and  thus 
aggravate  any  tendency  that  exists  toward  the  development  of  a 
near-sighted  condition. 


DIOPTRICS    OF    THE    EYE. 


321 


In  hypermetropia  the  conditions  are  the  opposite  of  those  in 
myopia.  Parallel  rays  of  light  after  refraction  in  the  eye  cut  the 
retina  before  they  come  to  a  focus.  The  principal  focal  distance,  in 
other  words,  is  behind  the  retina.  In  this  case,  also,  each  point 
of  a  distant  object  will  make  upon  the  retina,  when  the  eye  is  not 
accommodated,  a  diffusion  circle,  and  the  image  consequently  is 
blurred.  This  defect  may  be  caused  by  a  lessened  curvature  or 
refractive  power  in  the  cornea  or  lens,  but  in  the  majority  of  cases 
it  is  referable  to  a  diminution  in  the  anteroposterior  diameter  of 
the  eyeball.  This  condi- 
tion is  usually  congenital: 
the  eyeball  from  birth  is 
smaller  than  the  normal. 
The  path  of  the  parallel 
rays  in  this  case  is  repre- 
sented in  the  diagram  C, 
Fig.  132.  When  such  an 
eye  looks  at  a  distant  ob- 
ject a  clear  image  may  be 
obtained  only  by  using  the 
ciliary  muscle,  and  to  pre- 
vent this  constant  strain 
upon  the  muscle  of  accom- 
modation convex  glasses 
must  be  worn.  Glasses  of 
this  kind  converge  the 
rays  and  if  properly  chosen 
will  bring  parallel  rays  to 
a  focus  without  the  con- 
stant aid  of  accommoda- 
tion. It  is  obvious  that 
in  the  hypermetropic  eye 
there  is  no  far  point  of 
distinct  vision  when  the 
eye  is  at  rest,  since  some 
accommodation  must  be 
used  to  bring  even  parallel  rays  to  a  focus.  The  near  point  of 
distinct  vision  will  be  farther  away  than  in  the  normal  eye,  since 
accommodation  begins  when  the  rays  are  parallel  and  its  limits 
are  reached  with  a  less  degree  of  divergence;  hence  the  name  of 
far-sightedness. 

Presbyopia  or  old-sigh tedness  has  been  referred  to  above.     It 
is  due  to  a  gradual  failure  in  the  effectiveness  of  accommodation 
with  increasing  age,  and  is  attributed  usually  to  a  progressive  in- 
crease of  rigidity  in  the  lens.     The  near  point  of  distinct  vision 
21 


Fig.  132.— Diagram  showing  the  difference  be- 
tween normal  (A),  myopic  (£),  and  hypermetropic 
(C)  eyes.  In  B  and  C  the  dotted  lines  represent  the 
path  of  the  rays  after  correction  by  glasses. — (.B&w- 
ditch.') 


322  THE  SPECIAL  SENSES. 

recedes  farther  and  farther  from  the  eye,  and  consequently  in  close 
work  convex  glasses  must  be  worn  to  aid  the  accommodation.  It 
is  obvious  that  this  effect  of  old  age  will  be  less  noticeable  in  the 
myopic  than  in  the  emmetropic  eye,  since  in  the  former  the  greater 
length  of  the  eyeball  requires  less  accommodation  in  near  vision  and 
the  failure  of  the  lens  to  refract  is  therefore  not  felt  so  soon  What 
is  known  as  second-sight  in  the  old  may  be  brought  about  by 
the  late  development  of  a  myopic  condition, — that  is,  by  a  change 
in  the  length  of  the  eyeball  or  by  a  swelling  of  the  crystalline 
lens, — and  in  such  a  case  convex  glasses  for  near  work  may  be 
dispensed  with. 

Astigmatism. — In  a  perfectly  normal  or  ideal  eye  the  refractive 
surfaces,  cornea,  anterior  and  posterior  surfaces  of  the  lens,  are 
sections  of  true  spheres,  and,  all  the  meridians  being  of  equal 
curvature,  the  refraction  along  these  different  meridians  is  equal. 
Such  an  eye  will  bring  the  cone  of  rays  proceeding  from  a  luminous 
point  to  a  focal  point  on  the  retina,  barring  the  disturbing  influence 
of  chromatic  and  spherical  aberration.  If,  however,  one  or  all  of  the 
refractive  surfaces  have  unequal  curvatures  along  different  merid- 
ians, then  it  is  obvious  that  the  rays  from  a  luminous  point  can  not 
be  brought  to  a  focal  point,  since  the  rays  along  the  meridian  of 
greater  curvature  will  be  brought  to  a  focus  first  and  begin  to  diverge 
before  the  rays  along  the  lesser  curvature  are  focused.  Such  a 
condition  is  designated  as  astigmatism  (from  a,  not,  and  aTtrna, 
point).  The  effect  may  be  illustrated  by  the  diagram  in  Fig.  133, 
which  represents  the  refraction  of  the  rays  from  a  luminous  point  by 
a  lens  whose  curvature  along  the  vertical  meridian  is  greater  than 
along  the  horizontal  meridian. 

The  rays  along  the  vertical  meridian  are  brought  to  a  focus 
first  at  (-r,but  those  from  the  horizontal  meridian  are  still  converging; 
so  that  a  screen  placed  at  this  point  will  give  the  image  of  a  horizontal 
line  (a-a'}.  The  rays  along  the  horizontal  meridian  are  brought  to  a 
focus  at  B,  but  those  from  focus  G  have  by  this  time  spread  out 
in  a  vertical  plane,  so  that  a  screen  placed  at  this  point  will  give 
the  image  of  a  vertical  line  (b-c).  In  between  the  images  will  be 
elliptical  or  circular,  as  represented  in  the  diagram.  In  the  eye 
astigmatism  may  be  due  to  an  inequality  in  curvature  of  either  the 
cornea  or  the  lens,  and  may  be  either  regular  or  irregular.  By 
regular  astigmatism  is  meant  that  condition  in  which  while  the 
curvature  along  each  individual  meridian  is  equal  throughout  its 
course,  the  curvatures  of  the  different  meridians  vary  regularly 
from  a  maximum  to  a  minimum,  and  in  such  a  way  that  the 
meridians  of  greatest  and  least  curvature  are  at  right  angles  to 
each  other  or  approximately  so.  In  other  words,  the  curvature 
of  the  refractive  surfaces  of  the  eye  is  such  as  would  be  obtained 
by  adding  a  cylindrical  to  a  spherical  lens.  Ordinary  astig- 


DIOPTRICS    OF    THE    EYE. 


323 


matism  is  of  the  regular  variety,  and  is  usually  attributed  to  a 
defect  in  the  curvature  of  the  cornea.  If  the  astigmatism  is  such 
that  the  vertical  meridian  has  the  greatest  curvature  it  is  termed 
"with  the  rule,"  since  usually  this  meridian  is  slightly  more 
curved  than  the  horizontal  one.  If,  on  the  contrary,  the  cur- 
vature along  the  horizontal  meridian  is  greater,  the  astigmatism 
is  "against  the  rule."  The  meridians  of  greatest  and  least  curva- 
ture may  not  lie  in  the  vertical  and  horizontal  planes,  but  in  some 
of  the  oblique  planes;  but  so  long  as  they  are  at  right  angles  the 
astigmatism  is  regular.  It  is.  evident  that  such  a  condition  may 
be  corrected  by  the  use  of  cylindrical  lenses,  so  chosen  as  to  in- 
crease the  refraction  along  the  meridian  in  which  the  cornea 
has  the  least  curvature,  in  which  case  a  convex  or  plus  cylinder  is 
used,  or.  on  the  other  hand,  to  diminish  appropriately  the  refraction 
along  the  meridian  of  greatest  curvature,  in  which  case  a  concave 
or  minus  cylinder  is  used.  An  eye  that  suffers  from  a  marked 


a 


Fig.  133. — Schema  to  illustrate  the  paths  of  the  rays  of  light  in  a  cornea  showing 
regular  astigmatism. — (McKendrick.)  The  lower  line  of  figures  represents  the  section  of 
the  cone  of  light,  or  the  images  obtained  at  different  distances.  The  image  varies  from  a 
horizontal  to  a  vertical  line,  but  at  no  place  can  a  point  be  obtained  at  which  rays  along 
all  meridians  are  focused. 

degree  of  astigmatism  cannot  focus  distinctly  at  the  same  time 
lines  that  are  at  right  angles  to  each  other;  hence,  the  use  of  a 
series  of  lines  whose  images  are  formed  along  the  different  merid- 
ians of  the  eye,  as  shown  in  Fig.  134,  may  be  used  to  reveal  this 
defect  if  it  exists.  If  one  looks  at  such  a  chart  through  a  convex 
lens,  e.  g.,  a  lens  of  5  or  10  diopters,  and,  starting  from  a  distance 
at  which  the  lines  are  all  blurred,  brings  it  gradually  nearer  to 
the  eye,  it  will  be  observed,  if  the  eye  is  astigmatic,  that  the  lines 
do  not  all  come  into  focus  at  once.  If  one  meridian,  for  example, 
that  of  90°,  comes  into  focus  first,  then  at  that  distance  the  mer- 
idian at  right  angles,  180°,  will  appear  most  blurred.  A  normal 


324 


THE    SPECIAL    SENSES. 


eye  can  be  thrown  into  an  astigmatic  condition  by  approximating 
the  eyelids  closely.  In  this  position  the  tears  make  a  concave 
cylindrical  lens,  which  alters  the  curvature  along  the  vertical 
meridian.  What  is  known  as  irregular  astigmatism  is  due  to 
the  fact  that  the  meridians  of  greatest  and  least  curvature  are 
not  at  approximately  right  angles,  or,  as  is  more  commonly 
the  case,  it  is  due  to  an  irregularity  in  the  curvature  along  some 
one  meridian,  such  as  may  be  produced  by  a  scar  upon  the  cor- 
nea. This  condition  may  be  produced  from  a  variety  of  causes 
affecting  either  the  cornea  or  the  lens,  and  practically  it  can- 
not be  corrected  by  the  use  of  lenses.  As  Helmholtz  has  shown, 

a  small  degree  of  irregular 
astigmatism  is  present  nor- 
mally, owing  to  a  certain 
asymmetry  in  the  curvature 
of  the  lens.  This  defect  is 
made  apparent  in  the  visual 
sensations  caused  by  a  point 
of  light,  such  as  is  furnished, 
for  instance,  by  a  fixed  star. 
The  retinal  image  in  these 
cases,  instead  of  being  a  sym- 
metrical point,  is  a  radiate 
figure  the  exact  form  of 
which  may  vary  in  different 
eyes.  For  this  reason  the 
fixed  stars  give  us  the  well- 
known  star-shaped  image 
instead  of  a  clearly  defined 
point. 

Innervation  and  Physiological  Control  of  the  Ciliary  Muscle 
and  the  Muscles  of  the  Iris. — From  an  optical  point  of  view  the 
iris  plays  the  part  of  a  diaphragm.  It  is,  moreover,  an  adjustable 
diaphragm  the  aperture  of  which — that  is,  the  size  of  the  pupil — 
is  varied  reflexly  according  to  the  conditions  of  illumination.  Its 
adjustments  are  made  possible  by  the  fact  that  it  contains  within 
its  substance  two  bands  of  muscular  tissue,  one,  the  sphincter 
muscle,  forming  a  circular  ring  whose  contraction  diminishes  the 
aperture  of  the  pupil,  and  the  other  a  dilator  muscle  whose  contrac- 
tion widens  the  pupil.  Each  of  these  muscles  possesses  its  own 
nerve  fibers  that  arise  ultimately  from  the  brain,  and  through  these 
fibers  reflex  movements  of  great  delicacy  are  effected.  The  sphinc- 
ter pupillae  is  a  well-defined  band  of  plain  muscle  whose  width 
varies,  according  to  the  state  of  contraction,  from  0.6  to  1.2  mms.; 
it  forms  a  ring  lying  just  on  the  margin  of  the  pupil,  and  it  is  im- 
bedded in  the  stroma  of  the  iris.  The  histological  differentiation 


Fig.  134. — Astigmatic  chart. 


DIOPTRICS    OF    THE    EYE. 


325 


of  the  dilator  pupillae  is  much  less  distinct.  For  a  long  time  its 
existence  was  the  subject  of  controversy,  but  it  is  now  conceded 
that  such  a  muscle  is  present  in  the  form  of  a  layer  of  elongated 
spindle-like  cells  which  lie  close  to  the  pigment  layer  of  the  iris  and 
form  radial  bundles  stretching  from  the  ciliary  border  of  the  iris 
toward  the  pupillary  orifice.*  Both  of  these  muscles  are  supplied 
by  autonomic  nerve  fibers — that  is,  the  motor  nerve  path  comprises 
a  pregangl ionic  fiber,  arising  from  the  central  nervous  system, 
and  a  postganglionic  fiber,  arising  from  a  sympathetic  ganglion. 
Anatomically  it  can  be  shown  that  the  sphincter  muscle  is  supplied 
by  the  short  ciliary  nerves  arising  from  the  ciliary  ganglion, 
which  supply  also  the 
muscle  of  accommoda- 
tion, the  ciliary  muscle; 
while  the  dilator  muscle 
is  supplied  by  the  long 
ciliary  nerves  that  arise 
from  the  ophthalmic 
branch  of  the  fifth  cra- 
nial nerve,  as  represented 
in  Fig.  135.  The  entire 
course  of  the  motor 
paths,  preganglionic  and 
postganglionic  fibers,  is 
represented  diagrammat- 
ically  in  Fig.  136.  The 
motor  fibers  to  the  ciliary 
muscle  and  sphincter 
pupillse  arise  in  the  mid- 
brain  in  the  nucleus  of 
origin  of  the  third  cranial 
nerve,  and  indeed  in  a 
special  part  of  this  nu- 
cleus lying  most  ante- 
riorly. They  leave  the 
third  nerve  in  the  orbit 
and  end  within  the  sub- 
stance of  the  ciliary  gan- 
glion, whence  the  path 
is  continued  by  sympa- 
thetic ( postganglionic ) 
fibers  emerging  from  the 
ganglion  in  the  short  ciliary  nerves.  The  fibers  to  the  dilator 


1C 


Course  of  constrictor  nerve  fibers, 
Course  of  dilator  nerve  fibers,-  - 


Fig.  135. — Diagrammatic  representation  of  the 
nerves  governing  the  pupil  (after  Foster) :  II,  Optic 
nerve;  e.g,  ciliary  ganglion;  r.b,  its  short  root  from 
///,  motor  oculi  nerve;  sym.,  its  sympathetic  root;  rl, 
its  long  root  from  V,  ophthalmonasal  branch  of  oph- 
thalmic division  of  fifth  nerve;  s.c,  short  ciliary 
nerves;  l.c,  long  ciliary  nerves. 


*  For  a  physiological  proof  and  the  literature  of  the  controversy  see 
Langley  and  Anderson,  "Journal  of  Physiology/'  13,  554,  1892.  For  the 
histological  proof,  Grunert,  "Archives  of  Ophthalmology."  30,  377,  1901. 


326 


THE    SPECIAL    SENSES. 


muscle  have  a  very  different  path.  They  arise  also  in  the  brain, 
most  probably  in  the  midbrain,  although  their  exact  origin  has 
not  been  determined  satisfactorily,  and  pass  down  the  spinal 
cord  to  terminate  in  the  lower  cervical  region.  From  this  point 
the  path  is  continued  by  spinal  neurons  which  leave  the  cord  in  the 
eighth  cervical  and  the  first  and  second  thoracic  spinal  nerves  and 
pass  by  way  of  the  corresponding  rami  communicantes  into  the 
sympathetic  chain  at  the  level  of  the  first  thoracic  ganglion.  From 
this  point  the  fibers  pass  upward  in  the  cervical  sympathetic  with- 
out terminating  until  they  reach  the  superior  cervical  ganglion  near 
the  base  of  the  skull.  From  this  ganglion  the  path  is  continued 
by  sympathetic  (postganglionic)  fibers  which  pass  to  the  Gasserian 
ganglion  and  unite  with  its  ophthalmic  branch.  Subsequently 
they  leave  the  ophthalmic  nerve  in  the  long  ciliary  branches.  These 
fibers  under  normal  conditions  are  in  constant  (tonic)  activity,  so 
that  if  the  path  is  interrupted  at  any  point — by  section  of  the  cervi- 


Gasserian, 
Ganqlion~ 


Lory  ciliary  nerve*. 
C. 


Superior  Cervical/ 

-•»••& 


Ciliary  Tieroes 


Cervical 
otympalhetie 


Fig.  136. — Schema  showing  the  path  of  the  preganglionic  and  postganglionic  fibers 
to  the  ciliary  muscle  and  to  the  sphincter  and  dilator  muscles  of  the  iris. — (Modified  from 
Schultz.)  The  course  of  the  long  ciliary  nerves  is  represented  very  diagrammatically. 

cal  sympathetic,  for  instance — the  pupil  is  seen  to  contract.  This 
constant  activity  may  be  referred  directly  to, the  activity  of  the 
spinal  neurons  whose  cells  lie  in  the  spinal  cord  in  the  lower  cervical 
and  upper  thoracic  region.  The  cells  in  question  constitute  what 
is  sometimes  called  the  lower  ciliospinal  center  of  Budge. 

The  Accommodation  Reflex  and  the  Light  Reflex  of  the 
Sphincter  Muscle. — When  the  eye  is  accommodated  for  a  near 
object  by  the  contraction  of  the  ciliary  muscle  there  is  always  a 
simultaneous  contraction  of  the  sphincter  pupillse  whereby  the 
pupil  is  narrowed.  The  act  is  one  of  obvious  value  in  vision,  since 
by  diaphragming  down  the  lens  the  focus  is  improved  and  more 
exact  vision,  such  as  is  needed  in  close  work,  is  obtained.  The  act 


DIOPTRICS    OF    THE    EYE.  327 

is  usually  spoken  of  as  the  accommodation  reflex,  but  in  reality  it 
is  rather  what  is  known  as  an  associated  movement.  The  act 
of  accommodation  carries  with  it  the  constriction  of  the  pupil, 
because,  in  all  probability,  the  efferent  discharge  from  the  cells 
in  the  midbrain  controlling  the  ciliary  muscle  affects  likewise  the 
neighboring  center  for  the  sphincter  muscle.  An  example  of 
a  similar  associated  action  is  seen  in  the  effect  of  the  respiratory 
movements  on  the  rate  of  heart  beat,  the  inspiratory  discharge 
from  the  respiratory  center  being  accompanied  by  an  associated 
effect  upon  the  cardio-inhibitory  center  whereby  the  heart  rate 
is  quickened.  In  the  particular  case  that  we  are  dealing  with 
three  muscular  acts,  in  fact,  are  usually  associated,  for  every  act 
of  accommodation  under  normal  circumstances  is  accompanied 
not  only  by  a  constriction  of  the  pupil,  but  also  by  a  convergence 
of  the  eyeballs,  due  to  a  contraction  of  the  internal  rectus  muscle 
in  each  eye. 

The  light  reflex  is  observed  when  light  is  thrown  into  the  eye. 
As  is  well  known,  the  pupil  dilates  in  darkness  or  dim  lights  and 
contracts  to  a  pin-point  upon  strong  illumination  of  the  retina. 
The  value  of  this  reflex  is  also  obvious.  In  the  dim  light  the  total 
illumination  and  therefore  the  visual  power  of  the  retina  is  aided 
by  an  enlarged  pupil,  but  in  strong  lights  the  illumination  may  be 
diminished  with  advantage  by  diaphragming,  since  the  optical 
image  on  the  retina  is  thereby  improved  on  account  of  the  diminu- 
tion in  spherical  aberration.  The  reflex  arc  involved  in  this  act  is 
known  in  part.  The  afferent  path  is  along  the  optic  nerve;  the 
efferent  path  back  to  the  sphincter  is  through  the  third  nerve 
and  ciliary  ganglion;  injury  to  either  of  these  paths  diminishes  or 
destroys  the  reflex.  The  reflex  is  also  lost  in  some  cases  in  which 
neither  of  these  paths  seems  to  be  involved.  In  tabes  dorsalis 
(locomotor  ataxia)  and  general  paresis,  for  instance,  the  pupil 
of  the  eye  is  constricted  and  does  not  give  the  light  reflex,  but 
still  shows  the  accommodation  reflex.  Such  a  condition  is  known 
as  the  Argyll  Robertson  pupil.  Some  question  exists,  there- 
fore, as  to  the  nature  of  the  connections  in  the  brain  between  the 
afferent  impulses  and  the  motor  center  in  the  nucleus  of  the  third 
nerve.  According  to  some  authors,  the  afferent  light  reflex  fibers 
are -a  set  of  fibers  distinct  from  the  visual  fibers  proper.  They 
arise  in  the  retina  and  pass  backward  in  the  optic  nerve,  but 
leave  the  optic  tracts  at  the  chiasma  to  enter  the  walls  of  the 
third  ventricle  and  thus  reach  the  nucleus  of  the  third  nerve. 
This  view,  however,  finds  no  support  in  the  histological  structure 
of  the  retina.  In  the  foveal  region  at  least  we  must  suppose  that 
stimulation  of  the  cones  gives  rise  to  both  the  visual  sensation 
and  the  pupil  reflex,  but  it  is  said  that  in  some  cases*  (amauroeis) 
*  Behr,  "Archiv  f.  Ophthalmologie,"  86,  468,  1913. 


328  THE    SPECIAL    SENSES. 

the  pupil  reflex  may  be  obtained  without  accompanying  visual 
sensations.  Under  normal  conditions  the  light  reflex  is  bi- 
lateral,— that  is,  light  thrown  upon  one  retina  only  will  cause 
constriction  of  the  pupil  in  both  eyes.  In  the  lower  animals, 
whose  optic  nerves  cross  completely  in  the  chisrna,  the  light 
reflex,  on  the  contrary,  is  unilateral,  affecting  only  the  eye  that 
is  stimulated.*  We  may  conclude,  therefore,  that  the  bilaterality 
of  the  reflex  in  the  higher  animals  is  dependent  upon  the  partial 
decussation  of  the  optic  fibers  in  the  chiasma,  a  sensory  stimulus 
upon  one  retina  giving  rise  to  impulses  which  are  conveyed  to  the 
two  sides  of  the  brain.  It  is  possible,  however,  that  in  addition 
commissural  connections  may  exist  between  the  central  connections, 
— the  motor  centers  in  the  midbrain.  It  is  usually  stated  that 
the  effect  of  the  light  upon  the  sphincter  muscle  is  greatest  when 
the  retina  is  stimulated  at  or  near  the  fovea  and  that  it  varies 
directly  with  the  intensity  of  the  light  and  the  area  illuminated.t 
The  Action  of  Drugs  upon  the  Iris. — The  condition  of  con- 
striction of  the  pupil  is  frequently  designated  as  miosis  (mi-o'-sis) 
and  the  condition  of  dilatation  as  mydriasis  (myd-ri'-as-is).  Many 
drugs  are  known  which,  when  applied  directly  to  the  absorptive 
surfaces  of  the  eye  or  when  injected  into  the  circulation,  affect 
the  muscles  of  the  iris  and  therefore  vary  the  size  of  the  pupil. 
Those  drugs  that  cause  miosis  are  spoken  of  as  miotics,  and  those 
that  produce  mydriasis  as  mydriatics.  Atropin,  the  active  prin- 
ciple of  belladonna,  homatropin,  and  cocain  are  well-known  myd- 
riatics, while  physostigmin  (eserin)  and  muscarin  or  pilocarpin  are 
examples  of  the  miotics.  There  has  been  much  question  as  to  the 
precise  action  of  these  drugs.  For  an  adequate  discussion  of  this 
question  the  student  is  referred  to  works  on  pharmacology;  but 
it  may  be  said  that  the  evidence  from  the  physiological  sidej  indi- 
cates that  atropin  causes  mydriasis  by  paralyzing  the  endings  of 
the  constrictor  nerve  fibers  in  the  sphincter  muscle,  while  phy- 
sostigmin and  muscarin  cause  miosis  by  stimulation  of  the  endings 
of  these  same  fibers. §  In  the  case  of  cocain  it  is  probable  that  the 
drug  first  stimulates  mainly  the  endings  of  the  dilator  fibers  in  the 
dilator  muscles,  and  in  stronger  doses  causes  additional  mydriasis 
by  paralyzing  the  constrictor  fibers.  The  stronger  mydriatics 
paralyze  not  only  the  sphincter  pupillse,  but  also  the  similarly 
innervated  ciliary  muscle,  thus  destroying  the  power  of  accom- 
modation. When  atropin  is  applied  to  the  eye  the  individual  is 

*  Steinach,  "Archiv  f.  d.  gesammte  Physiologie,"  47,  313,  1890. 

fSee  Abelsdorff  and  Feilchenfell,  "Zeitschrift  f.  Psychologie  und  Phys- 
iologie des  Sinnesorgane,"  34,  111,  1904. 

J  Schultz,  "Archiv  f.  Physiologie,"  1898,  47. 

|  According  to  Langley,  "Journal  of  Physiology,"  39,  235,  1909,  the  stim- 
ulating or  paralyzing  effect  of  such  drugs  is  due  to  an  action  not  on  the  nerve 
terminals,  but  on  a  special  receptive  substance  in  the  muscle-fibers. 


DIOPTRICS    OF    THE    EYE.  329 

unable  to  use  his  eyes  for  near  work — reading,  for  example — until 
the  effect  of  the  drug  has  worn  off.  In  ophthalmological  literature 
this  condition  of  paralysis  of  the  ciliary  muscle  is  spoken  of  as 
cycloplegia,  and  most  of  the  mydriatic  drugs  are  also  cycloplegics. 
On  the  contrary,  the  stronger  miotics  stimulate  the  ciliary  muscle, 
and  therefore  during  their  period  of  action  throw  the  eye  into  a 
condition  of  forced  accommodation. 

The  Balanced  Action  of  the  Sphincter  and  Dilator  Muscles 
of  the  Iris. — It  would  seem  that  under  normal  conditions  both  the 
sphincter  and  the  dilator  muscle  are  kept  more  or  less  in  tonic 
activity  by  impulses  received  through  their  respective  motor  fibers. 
They  thus  balance  each  other,  to  speak  figuratively,  and  a  mechan- 
ism of  this  kind  in  which  two  opposing  actions  are  in  play  is  in  a 
condition  to  respond  promptly  and  smoothly  to  an  excess  of  stimu- 
lation from  either  side.  The  two  muscles,  in  fact,  act  as  antago- 
nists in  the  same  manner  as  the  flexor  and  extensor  muscles  around 
a  joint.  At  the  same  time  this  relation  adds  some  difficulties  to 
the  explanation  of  specific  reactions,  since  it  is  evident  that  a  dila- 
tation of  the  pupil  may  be  caused  either  by  a  contraction  of  the 
dilator  muscle  or  a  loss  of  tone  (inhibition)  in  the  sphincter,  while 
in  constriction  of  the  pupil  the  effect  may  result  either  from  a  con- 
traction of  the  sphincter  or  an  inhibition  of  the  dilator;  or,  lastly, 
the  contraction  of  one  muscle  may  always  be  accompanied  by  an 
inhibition  of  its  antagonist,  as  is  supposed  to  be  the  case  with  the 
flexor  and  extensor  muscles  of  the  limbs  (law  of  reciprocal  in- 
nervation).  Anderson*  has  given  some  evidence  to  show  that  the 
dilatation  of  the  pupil  in  cats  is  due  to  a  double  action  of  this 
sort,  the  pupillodilator  muscle  contracting  first  and  subsequently 
the  tone  of  the  constrictors  suffering  an  inhibition.  Alterations 
in  the  size  of  the  pupil  take  place  not  only  under  the  conditions 
described  above — namely,  the  light  and  the  accommodation 
reflex  and  the  action  of  drugs — but  also  under  many  other  cir- 
cumstances, normal  and  pathological.  In  sleep,  for  instance, 
the  eyes  roll  upward  and  outward  and  the  pupils  are  constricted. 
The  miosis  in  this  case  may  be  due  to  a  cessation  in  tonic  activity 
on  the  part  of  the  dilator  muscle,  or  to  an  increased  tonus  of  the 
sphincter  muscle.  The  latter  explanation  is  strengthened  by  the 
fact  that  experiments  indicate  that  during  the  waking  period  the 
tonus  of  the  cranial  center  controlling  the  sphincter  is  kept  under 
inhibition  by  the  inflow  of  sensory  impulses.  During  sleep  this 
central  inhibition  diminishes  or  disappears.  Emotional  states  also 
affect  the  size  of  the  pupil  and  thus  aid  in  giving  the  facial  expres- 
sions characteristic  of  these  conditions.  Writers  speak  of  the 
eyes  dilating  with  terror  or  darkening  with  emotions  of  deep  pleas- 
ure. This  pupillary  accompaniment  of  the  emotional  states  may 
*  "Journal  of  Physiology,"  30,  15.  1903. 


330  THE  SPECIAL  SENSES. 

occur  even  when  it  is  a  matter  of  memory  rather  than  immediate 
experience.  The  explanation  of  this  mydriasis  can  hardly  be  ob- 
tained by  experiment.  So  far  as  the  physiological  mechanisms  are 
concerned,  it  may  be  explained  either  by  a  stimulation  of  the  dilator 
muscle  or  by  an  inhibition  of  the  tonus  of  the  constrictor  muscle. 
In  favor  of  the  latter  explanation  we  have  the  fact  that  stimula- 
tion of  the  cortex  cerebri  causes  dilatation  when  the  dilator  paths 
are  severed. 

Intraocular  Pressure. — The  liquids  in  the  interior  of  the 
eye  are  normally  under  a  pressure,  the  average  value  of  which 
may  be  estimated  at  25  mms.  of  mercury.  In  consequence  of 
this  internal  pressure  the  eyeball  is  tense  and  its  external  surface, 
including  the  cornea,  shows  a  regular  curvature.  It  is  obvious 
that  folds  or  creases  in  the  cornea  would  entirely  destroy  its  use- 
fulness, so  far  as  the  formation  of  an  image  is  concerned.  The 
amount  of  the  intraocular  pressure  may  be  measured  by  thrusting 
a  tubular  needle,  properly  connected  with  a  manometer,  into  the 
anterior  chamber  of  the  eye.  The  liquid  in  the  interior  of  the 
eyeball  may  be  considered  as  tissue  lymph,  and  like  the  lymph 
elsewhere  it  is  derived  from  the  blood-plasma.  Investigation 
has  shown  that  the  lymph  is  formed  in  the  ciliary  processes,  but 
in  this  as  in  other  cases  there  is  a  difference  of  opinion  as  to  whether 
the  production  is  due  to  so-called  secretory  or  to  mechanical 
causes,  such  as  filtration.*  We  may  suppose  that  the  liquid  filters 
into  the  eye  through  the  vessels  in  the  ciliary  processes,  and,  on 
the  other  hand,  drains  off  or  is  absorbed  at  the  angle  of  the  anterior 
chamber  through  the  vein  known  as  the  canal  of  Schlemm.  The 
intraocular  pressure  rises  until,  under  its  influence,  the  outflow 
just  balances  the  inflow.  It  is  evident  from  this  point  of  view 
that  intraocular  pressure  will  be  increased  by  any  change  that 
will  augment  the  production  of  the  liquid  at  the  ciliary  processes, 
such  as  a  rise  of  blood-pressure,  or  by  any  interference  with  the 
outflow,  such  as  might  arise  from  a  blocking  of  the  canal  of 
Schlemm.  Certain  pathological  conditions  (glaucoma)  are  char- 
acterized by  an  abnormally  high  intraocular  tension,  the  differ- 
ence from  the  normal  being  such  that  it  is  easily  recognized  by 
pressure  with  the  fingers. 

Methods  of  Determining  the  Refraction  of  the  Eye. — The  condition 
of  the  eye  as  regards  its  refraction  may  be  determined  by  the  use  of  suitable 
charts  and  a  series  of  spherical  and  cylindrical  lenses.  The  results  by 
such  a  method  depend  largely  upon  the  statements  of  the  patient,  that 
is  to  say,  they  are  largely  subjective.  A  number  of  instruments  have  been 
devised,  however,  by  means  of  which  the  refraction  of  the  eye  may  be  studied 

*  For  discussion  and  literature,  see  Henderson  and  Starling,  "Proceed- 
ings Royal  Society,"  1906,  B.  vol.  77;  Hill  and  Flack,  ibid.,  vol.  85,  1912,  and 
Henderson,  "Glaucoma,"  London,  1910. 


DIOPTRICS    OF    THE    EYE. 


331 


in  a  purely  objective  way,  so  far  as  the  patient  is  concerned.  The  most 
important  of  these  instruments  are  the  ophthalmoscope,  the  retinoscope  or 
skiascope,  and  the  ophthalmometer.  A  brief  description  is  given  of  each  of 
these  instruments,  but  for  the  numerous  practical  details  necessary  to  their 
successful  use  reference  must  be  made  to  special  manuals. 

The  Ophthalmoscope. — The  light  that  falls  into  the  eye  is  partly  absorbed 
by  the  black  pigment  of  the  choroid  coat,  and  is  partly  reflected  back  to  the 
exterior.  This  latter  portion  is  reflected  back  in  the  direction  in  which  it 
entered.  Merely  holding  a  light  near  the  eye  does  not,  therefore,  enable  us  to 
see  the  interior  more  clearly,  since  in  order  to  catch 
the  returning  rays  in  our  own  eye  it  would  be  neces- 
sary to  interpose  the  head  between  the  source  of 
light  and  the  observed  eye.  If,  however,  we  could 
arrange  the  light  to  enter  the  observed  eye  as 
though  it  proceeded  from  our  own  eye,  then  the 
returning  rays  would  be  perceived,  and  with  suf- 
ficient illumination  the  bottom  or  fundus  of  the 
observed  eye  might  be  seen.  Arguing  in  this  way 
Helmholtz  constructed  his  first  form  of  the  oph- 
thalmoscope in  1851.  The  value  of  the  ophthal- 
moscope is  twofold:  It  enables  the  observer  to 
examine  the  interior  of  the  eye  and  thus  recognize 
diseased  conditions  of  the  retina;  it  is  also  useful 
in  detecting  abnormalities  in  the  refractive  sur- 
faces of  the  eye.  The  principle  of  the  instrument 
is  well  represented  in  the  original  form  devised  by 
Helmholtz,  as  shown  schematically  in  Fig.  138,  A. 
I  represents  the  observed  eye  and  II  the  eye  of  the 
observer.  Between  the  two  eyes  is  placed  a  piece 
of  glass  inclined  at  an  angle.  Light  from  the  can- 
dle falling  upon  this  glass  is  in  part  reflected  from 
the  surface  to  enter  eye  7,  and  these  rays  on 
emerging  from  the  eye  along  the  same  line  pass 
through  the  glass  in  part  and  enter  eye  //.  In 
place  of  the  plane  unsilvered  glass  it  is  now  cus- 
tomary to  use  a  concave  mirror  with  a  small  hole 
through  the  center,  the  observer's  eye  being  placed 
directly  behind  this  hole.  Such  an  instrument  is 
shown  in  Fig.  137.  The  instrument  is  used  in  two 
ways,  known  as  the  direct  and  the  indirect  method. 
In  the  direct  method  the  mirror  is  held  very  close 
to  the  observed  eye,  and  the  paths  of  the  rays  of 
light  into  and  out  of  the  eye  are  represented 
schematically  in  Fig.  138,  B.  The  light  from  a 
lamp  or  from  an  electrical  bulb  placed  within  the 
handle  of  the  ophthalmoscope  (Fig.  137)  is  caught 
upon  the  mirror  and  is  thrown  into  the  eye,  the 
rays  coming  to  a  focus  and  then  spreading  out  so 
as  to  give  a  diffuse  illumination  of  the  fundus. 
This  latter  surface  may  now  be  considered  as 
a  luminous  object  sending  out  rays  of  light. 

Taking  any  three  objects  on  the  retina,  A,  B,  G,  it  is  apparent  that  if  eye 
7  is  an  emmetropic  eye,  these  points  are  at  the  principal  focal  distance, 
and  the  rays  sent  from  each  after  emerging  from  the  eye  are  in  parallel 
bundles.  These  rays  penetrate  the  hole  in  the  mirror  and  fall  into  the  ob- 
server's eye  as  though  they  came  from  distant  objects.  If  the  observer's  eye 
is  also  emmetropic,  or  is  made  so  by  suitable  glasses,  these  bundles  of  rays 
will  be  focused  on  his  retina  without  an  act  of  accommodation.  He  must,  in 
fact,  in  looking  through  the  mirror,  gaze,  not  at  the  eye  before  him,  but,  re- 
laxing his  accommodation,  gaze  through  the  eye,  as  it  were,  into  the  distance. 
In  this  way  he  will  see  the  portion  of  the  retina  illuminated,  the  image  of  the 


Fig.  137.— De  Zeng  electric 
ophthalmoscope.  The  electric 
light  is  contained  in  the  handle 
of  the  instrument  and  its  light 
is  concentrated  on  the  mirror 
by  a  lens  seen  at  the  top  of  the 
handle.  Back  of  the  mirror 
is  a  rotating  disc  with  plus 
and  minua  lenses  of  different 
powers. 


332 


THE    SPECIAL    SENSES. 


objects  seen  being  inverted  on  his  own  retina  and  therefore  projected  or  seen 
erect.  If  the  observed  eye  is  myopic  its  retina  is  farther  back  than  the  prin- 
cipal focus  of  its  refracting  surfaces;  consequently  the  rays  sent  out  from  the 
illuminated  retina  emerge  in  converging  bundles  and  cannot  be  focused  on 
the  retina  of  the  observer's  eye.  By  inserting  a  concave  lens  of  proper  power 
between  his  eye  and  the  mirror  the  observer  can  render  the  rays  parallel  and 
thus  bring  out  the  image.  From  the  power  of  the  lens  used  the  degree  of  my- 
opia may  be  estimated.  Just  the  reverse  happens  if  the  observed  eye  is 
hypermetropic.  In  such  an  eye  the  retina  is  nearer  than  the  principal  focal 


Fig.  138.  —  Diagrams  to  represent  the  principle  of  the  ophthalmoscope  :  A,  The  orig- 
inal form  of  ophthalmoscope,  consisting  of  a  piece  of  glass,  M,  inclined  at  a  suitable  angle. 
The  rays  from  the  source  of  light  are  reflected  into  the  observed  eye,  /,  and  thence  return 
along  the  same  lines  passing  through  M  to  reach  the  9bserver's  eye,  //.  B,  the  direct 
method  with  the  ophthalmoscopic  mirror.  The  rays  of  light  illuminate  the  fundus  of  the 
observed  eye,  /,  and  thence  pass  out  in  parallel  rays,  if  the  eye  is  emmetropic,  to  reach  the 
observer's  eye,  //.  C,  the  indirect  method  with  ophthalmoscopic  mirror  and  intercalated 
lens.  The  rays  of  light-red  lines  are  brought  to  a  focus  within  the  anterior  chamber  of  the. 
eye  and  thence  diverge  to  give  a  general  illumination  of  the  interior  of  the  eyeball.  The 
returning  rays  of  light  are  indicated  for  a  single  point,  6.  At  a',  6',  cf  ',  a,  real  inverted  image 
of  a  portion  of  the  retina  is  formed  in  the  air,  which  in  turn  is  focused  on  the  retina  of  the 
observer's  eye. 


distance  of  the  refractive  surface;  consequently  the  light  emitted  from  the 
retina  emerges  in  bundles  of  diverging  rays  which  cannot  be  brought  to  a 
focus  on  the  retina  of  the  observer  unless  he  exerts  his  own  power  of  accom- 
modation or  interposes  a  convex  lens  between  his  eye  and  the  mirror. 

The  indirect  method  of  using  the  ophthalmoscope  is  represented  in  Fig. 
138,  C.  The  mirror  is  held  at  some  distance,  at  arm's  length,  from  the  ob- 
served eye,  7,  while  just  before  this  eye  a  biconvex  lens  of  short  focus  is 
placed.  As  shown  in  the  diagram  by  the  red  lines,  the  reflected  light  from 
the  mirror  comes  to  a  focus  and  then  diverging  falls  upon  the  biconvex  lens. 
This  lens  brings  the  rays  to  a  focus  at  or  near  the  eye,  whence  they  again 
diverge  and  light  up  the  retina  with  a  diffuse  illumination.  The  light  from 


DIOPTRICS    OF   THE    EYE.  333 

this  retina  is  in  turn  sent  back  toward  the  mirror,  its  path  being  indicated  for 
the  point  b  by  the  black  lines.  If  the  eye  is  emmetropic  the  rays  from  this 
point  emerge  parallel,  and,  falling  upon  the  biconvex  lens,  are  brought  to  a 
focus  at  &'.  Similarly  the  rays  from  a  will  be  brought  to  a  focus  at  a'  and 
from  c  at  c'.  Consequently  there  will  be  formed  in  the  ah-  an  inverted  image, 
and  it  is  at  this  image  that  the  eye  of  the  observer  gazes  through  the  hole  in 
the  mirror.  This  image  forms  its  image  on  the  retina  of  the  observer's  eye, 
as  represented  in  the  diagram  at  a",  b",  c",  and  is  projected  outward  or  seen 
inverted  as  regards  the  original  position  of  the  points  in  the  retina  of  eye  /. 
The  indirect  method  gives  a  larger  field  than  the  direct  method,  although  the 
objects  seen  are  of  smaller  size. 

The  Retinoscope  or  Skiascope. — When  one  reflects  a  spot  of  light 
upon  a  wall,  any  movement  of  the  reflecting  (plane)  mirror  is  followed  by  a 
movement  of  the  reflected  spot  in  the  same  direction.  So  if  the  fundus  of  the 
eye  is  illuminated  by  a  plane  mirror  provided  with  a  peep-hole,  the  observer 
looking  through  this  hole  may  see  a  spot  of  light  reflected  from  the  retina 
and  can  determine  whether  the  spot  moves  in  the  same  direction  as  the 
mirror  or  against  it.  If  the  eye  under  observation  is  normal  (emmetropic), 
then  the  rays  of  light  starting  from  the  retina  will  emerge  in  parallel  bundles, 
since  the  retina  lies  at  the  principal  focal  distance,  and  as  the  mirror  is  tilted 
from  side  to  side  the  illuminated  spot  moves  in  the  same  direction.  By  placing 
a  convex  lens  of  suitable  focus  in  front  of  the  observed  eye  we  can  cause  the 
emerging  parallel  rays  to  come  to  a  focus  and  cross  before  reaching  the  ob- 
server's eye.  In  such  a  case  the  movements  of  the  spot  of  light  upon  the  retina 
will  be  against  those  of  the  mirror.  For  example,  let  us  suppose  that  the 
observing  eye  is  placed  just  1  meter  away  from  the  eye  observed,  then  if 
we  put  in  front  of  the  latter  a  convex  lens  of  1.25  D.  the  emerging  rays  will  be 
focused  at  a  point  25  ctm.  in  front  of  the  observer's  eye  and  the  movements 
of  the  spot  of  light  will  be  against  the  mirror.  A  lens  of  less  than  1  D.  placed 
in  front  of  the  observed  eye  would  not  bring  the  rays  to  a  focus  in  front  of 
the  observer's  retina,  consequently  the  movements  of  the  spot  would  be  with 
the  mirror.  Assuming  that  we  are  dealing  with  an  emmetropic  eye,  it  can 
be  shown  that  at  the  distance  mentioned  (1  meter)  any  lens  of  less  than 
1  D.  placed  in  front  of  the  eye  leaves  the  movements  with  the  mirror, 
while  any  lens  of  more  than  1  D.  gives  movements  against  the  mirror. 
Consequently  a  lens  of  just  1  D.  would  mark  the  exact  "point  of  rever- 
sal." With  a  lens  of  this  power  the  focus  would  fall  theoretically  just  on  the 
observer's  retina.  In  such  a  case  any  movement  of  the  mirror  would  be 
followed  by  the  appearance  or  disappearance  of  the  spot,  but  no  direction  of 
movement  would  be  perceived.  The  movements  of  the  spot  of  light  formed 
upon  the  retina  by  the  retinoscopic  mirror  may  be  used  to  determine  all  the 
various  abnormalities  of  refraction  of  the  eye  according  to  the  following 
general  schema  :  The  observer  sits  at  a  fixed  distance,  say  1  meter,  from 
the  patient,  and  determines  whether  the  reflected  spot  from  the  illuminated 
fundus  moves  with  or  against  the  mirror.  If  the  movement  is  with  the  mirror, 
then  the  eye  under  observation  is  either  normal  or  hyperopic  (or  if  myopic 
the  myopia  is  less  than  ID.).  By  placing  convex  lenses  in  front  of  the  eye 
the  observer  seeks  for  the  point  of  reversal.  If  this  point  is  given  by  a  lens 
of  +  ID.,  then  the  eye  under  examination  is  emmetropic  ;  if  a  stronger  lens 
is  required  the  eye  is  hyperopic,  that  is,  the  emerging  rays  are  divergent  and 
require  a  stronger  lens  to  bring  them  to  a  focus  before  reaching  the  observer's 
eye.  In  the  latter  case  the  amount  of  hyperopia  is  obtained  by  ascertaining 
the  strength  in  diopters  of  the  lens  required  to  just  reverse  the  movement 
and  subtracting  1  D.  from  it,  since  the  latter  amount  is  required,  at  a  distance 
of  1  meter,  to  get  reversal  with  the  normal  eye.  If  the  reversal  is  given  by 
a  convex  lens  of  less  than  ID.,  then  the  eye  is  myopic  to  an  extent  less  than 
1  D.  When  the  movements  of  the  spot  of  light  are  against  the  mirror 
from  the  beginning,  then  the  observer  is  dealing  with  a  myopic  eye  (the  myopia 
being  greater  than  1  D.).  To  reverse  the  movement  it  is  now  necessary  to 
place  concave  lenses  in  front  of  the  observed  eye  until  the  point  of  reversal 
is  obtained,  that  is,  until  the  focus  of  the  emerging  rays  falls  behind  the 


334  THE  SPECIAL  SENSES. 

retina  of  the  observer.  The  concave  lens  necessary  to  give  this  result,  plus  1  D. 
for  distance,  gives  the  extent  of  the  myopia  in  diopters.  With  astigmatic 
eyes  the  point  of  reversal  may  be  determined  for  the  different  meridians 
of  the  eye,  the  movements  of  the  mirror  being  in  the  same  meridian.  By 
the  character  of  the  reflected  spot  and  the  points  of  reversal  it  is  possible 
with  the  retinoscope  to  determine  the  principal  meridians,  and  the  difference 
in  refraction  between  them,  that  is,  the  degree  and  the  axis  of  the  astigmatism. 
The  Ophthalmometer.—  The  ophthalmometer  is  an  instrument  for 
measuring  the  curvature  of  the  refracting  surfaces  of  the  eye.  As  actually 
applied  in  practise  it  is  arranged  especially  for  measuring  the  curvatures 
of  the  cornea  along  its  different  meridians.  The  point  for  which  the  instru- 
ment is  designed  is  to  obtain  the  size  of  the  image  reflected  from  the  convex 
surface  of  the  cornea.  Any  luminous  object  placed  in  front  of  the  eye  will  give 
a  reflected  image  from  the  cornea  as  from  the  surface  of  a  convex  mirror. 
If  the  size  of  the  object  and  its  distance  from  the  cornea  are  known  and  the 
size  of  the  corneal  image  is  determined,  then  the  radius  of  curvature  of  the 

cornea  is  given  by  the  equation  r  =        n->  in  which  p  represents  the  distance  of 


T. 


Fig.  139. — Schema  to  indicate  the  general  principle  of  the  ophthalmometer :  T, 
Telescope  to  observe  the  reflected  images  from  the  cornea  ;  A  and  B,  the  targets  or  mires 
in  the  shield  at  a  known  distance  apart  whose  images  are  reflected  from  the  cornea  ;  a 
and  b,  the  reflected  images  of  A  and  B  on  the  cornea.  The  distance  a-6  has  to  be  determined. 

the  object  from  the  cornea,  i,  the  size  of  the  corneal  image,  and  o.  the  size 
of  the  object.  For  example,  let  A  and  B  in  Fig.  139  be  two  luminous  areas 
arranged  on  the  arc  of  a  circle.  If  placed  in  front  of  the  cornea  C  each 
will  give  a  reflected  image  a  and  b,  which  may  be  observed  by  means  of 
the  telescope  T.  The  distance  between  A  and  B  represents  the  size  of 
the  object  and  the  distance  between  a  and  b  the  size  of  the  image.  This 
latter  factor  is  determined  by  means  of  the  telescope.  A  scale,  for  in- 
stance, might  be  placed  in  the  eye-piece  of  the  telescope  and  the  distance 
a-6  be  determined  in  terms  of  its  graduation.  This  valuation  might  then  be 
converted  into  millimeters  by  substituting  a  scale  for  the  cornea  and  measuring 
off  upon  it  the  observed  distance  in  the  eye-piece  scale.  If  the  arc  carrying 
AB  is  arranged  so  that  it  may  be  rotated  it  is  obvious  that  the  size  of  the 
corneal  images  may  be  measured  for  the  different  meridians  and  thus  enable 
one  to  compare  their  curvatures.  In  modern  instruments,  such  as  is  repre- 
sented in  Fig.  140,  the  luminous  areas,  known  as  targets  or  mires,  are  placed  in  a 
spherical  shield  which  may  be  rotated  around  the  axis  of  the  telescope.  The 
shield  has  a  radius  of  curvature  of  0.35  meters  and  its  center  of  rotation  is 
approximately  coincident  with  that  of  the  cornea  when  the  eye  is  in  its 
proper  position.  The  reflected  images  of  the  mires  from  the  surface  of  the 


DIOPTRICS  OF  THE  EYE. 


335 


cornea  are  each  doubled,  when  viewed  through  the  telescope,  by  means  of 
a  double  vision  prism  of  Iceland  spar  and  the  displacement  'produced  in 
this  way  is  a  definite  amount  for  the  distance  chosen.  Four  images  of  the 
mires  are  thus  seen,  and  when  the  mires  are  properly  adjusted  for  a  cornea  of 
average  curvature  the  two  inner  images  are  in  contact  with  each  other. 
A  variation  from  this  average  is  indicated  by  an  overlapping  of  the  images, 


Fig.  140.— Ophthalmometer  (Hardy). 

the  value  of  which  in  diopters  or  in  radii  of  curvature  is  read  off  upon  the 
instrument.  The  instrument,  therefore,  when  once  calibrated  enables  one 
to  read  off  at  once  the  radii  of  curvature  for  the  different  meridians  and  thus 
determine  the  axis  and  degree  of  astigmatism.  It  should  be  added  that 
the  instrument  gives  only  the  curvatures  and  degree  of  astigmatism,  if  any 
exists,  of  the  cornea,  and  is  therefore  of  no  immediate  service  in  determining 
the  total  astigmatism,  that  is,  the  astigmatism  of  cornea  and  lens  acting 
together. 


CHAPTER  XVIII. 

THE  PROPERTIES  OF  THE  RETINA— VISUAL  STIMULI 
AND  VISUAL  SENSATIONS. 

The  Portion  of  the  Retina  Stimulated  by  Light.— The  normal 
stimulus  to  the  sensory  cells  in  the  retina  is  found  in  the  vibrations 
of  the  ether,  the  waves  of  light.  When  sunlight  is  passed  through  a 
prism  the  waves  of  different  lengths  are  dispersed,  and  those  capable 
of  stimulating  the  retina  form  the  visible  spectrum  extending  from 
red  to  violet.  The  limits  of  the  spectrum  are,  on  the  one  hand,  the 
extreme  red  rays  with  a  wave  length  of  7600,  measured  in  Ang- 
strom units  (1  Au  =  10,000,000  mm.),  and,  on  the  other,  the  ex- 
treme violet,  having  a  wave  length  of  about  3900.  The  part  of 
the  retina  stimulated  by  these  vibrations  is  supposed  to  be  the  layer 
of  rods  and  cones.  To  reach  these  structures  the  light  must  pass 


Fig.  141. — Demonstration  of  blind  spot,  left  eye  (Stifel's  figure):  Hold  the  black  circle  in 
front  of  the  left  eye  at  a  distance  of  about  10  inches.  Close  the  right  eye.  Place  a  pencil 
point  at  A  and  draw  it  slowly  along  the  line  ABC,  keeping  the  left  eye  on  the  pencil  point. 
At  a  certain  distance  beyond  A,  for  example,  at  B,  the  white  spot  in  the  black  circle  will  dis- 
appear (falls  on  the  blind  spot),  but  will  reappear  when  the  pencil  point  is  moved  further  out- 
ward, at  C  for  example.  By  marking  the  points  at  which  the  white  spot  disappears  and  re- 
appears the  diameter  of  the  spot  is  given  for  that  meridian  and  distance  of  projection.  In 
the  same  way  the  diameter  may  be  marked  for  the  other  meridians  and  the  form  of  the  blind 
spot  be  obtained. 

through  the  other  layers  of  the  retina.  That  the  rods  and  cones  are 
the  structures  that  react  to  the  light  stimulation  is  indicated  by 
their  structure  and  their  connections  and  by  such  facts  as  the  follow- 
ing: Under  certain  conditions,  which  are  described  below,  the 
shadows  of  the  retinal  vessels  and  the  contained  corpuscles  may  be 
seen,  a  fact  which  indicates  that  the  perceiving  structures  lie  ex- 
ternally to  these  vessels.  In  the  fovea  centralis,  in  which  vision  is 
most  perfect,  the  layers  of  the  retina  are  thinned  out  until  practically 
only  the  rods  and  cones  remain  to  be  acted  upon.  That  the  optic 

336 


PROPERTIES    OF    THE    RETINA.  337 

nerve  fibers  themselves  are  not  acted  upon  by  light  waves  is  proved 
by  the  existence  of  the  blind  spot.  The  termination  of  the  optic 
nerve  within  the  eyeball,  the  optic  disc,  lies  about  15  degrees  to  the 
nasal  side  of  the  fovea  and  has  a  diameter  of  about  1.5  mms.  From 
this  point  the  nerve-fibers  spread  out  over  the  rest  of  the  optic  cup 
to  form  the  internal  layer  of  the  retina.  But  the  optic  disc  itself  has 
no  retinal  structure,  and  light  that  falls  upon  it  is  not  perceived. 
The  presence  of  this  blind  spot  in  our  visual  field  is  easily  demon- 
strated by  the  experiment  illustrated  and  described  in  Fig.  141. 
In  the  visual  field  for  each  eye,  therefore,  there  is  a  gap  representing 
the  projection  of  the  area  of  the  optic  disc  to  the  exterior,  the  size 
of  the  gap  increasing  with  the  distance  from  the  eye.  We  do  not 
notice  this  deficiency,  inasmuch  as  it  exists  in  our  indirect  field  of 
vision  (see  below),  in  which  our  perception  of  form  is  poorly  de- 
veloped; so  that  any  disturbance  in  outline  that  might  result  in  the 
retinal  image  of  external  objects  is  unperceived.  Morever,  the 
portion  of  the  external  world  that  falls  on  the  blind  spot  of  one  eye 
may  fall  on  the  retinal  field  of  the  other,  and  be  perceived  in  binoc- 
ular vision.  It  is  to  be  borne  in  mind,  also,  that  the  projection  of 
the  blind  spot  does  not  appear  in  the  visual  field  as  a  dark  area;  it 
is  simply  an  absent  area,  so  that  no  gap  exists  in  our  consciousness  of 
the  spatial  relations  of  the  visual  field;  the  margins,  so  to  speak,  of 
the  hole  come  into  contact  so  far  as  our  consciousness  is  concerned. 
The  Action  Current  Caused  by  Stimulation  of  the  Retina. — 
The  effect  of  light  waves  falling  upon  the  retina  is  to  set  up  a  series 
of  nerve  impulses  in  the  optic  nerve  fibers.  It  is  interesting  to 
find  that  these  impulses  aroused  in  a  sensory  nerve  by  a  normal 
stimulus  are  attended  by  electrical  changes  similar  to  those  observed 
in  motor  fibers  when  stimulated  normally  or  artificially.  The  fact 
strengthens  the  view  that  the  electrical  change  is  an  invariable  ac- 
companiment of  the  nerve  impulse,  if  not  the  nerve  impulse  itself. 
If  the  eye  is  excised  and  connected  with  a  galvanometer  or  capillary 
electrometer  by  two  non-polarizable  electrodes,  one  placed  upon  the 
cut  end  of  the  optic  nerve  and  the  other  on  the  cornea,  the  usual 
demarcation  current  is  obtained  due  to  the  injury  to  the  optic  nerve. 
If  the  preparation  is  kept  in  the  dark  and  arrangements  are  made 
to  throw  a  light  through  the  pupil  upon  the  retina  the  galvanometer 
indicates  an  electrical  change  or  current  whenever  the  light  is 
admitted.*  The  direction  of  the  current  in  the  eyeball  is  from  the 
fundus  to  the  cornea,  and  as  regards  the  pre-existing  demarcation 
current  it  is  in  the  same  direction  and  forms,  therefore,  a  so-called 
positive  variation.  When  the  electrodes  are  placed  on  the  longi- 
tudinal and  the  cut  surface  of  the  optic  nerve,  then,  according  to 
Kuhne,  the  electrical  response  to  light  is  a  negative  variation  similar 

*  Dewar  and  McKendrick,  "  Transactions,  Royal  Society,  Edinburgh,"  27. 
1873;  Gotch,  "Journal  of  Physiology,"  29,  388,  1903,  and  31,  1,  1904. 
22 


338  THE  SPECIAL  SENSES. 

to  that  described  for  stimulation  of  nerves  in  general  (p.  102).  Not 
only  is  there  a  "light  response"  each  time  that  the  retina  is  stimu- 
lated by  light,  but  there  is  a  similar  electrical  change,  a  "dark 
response,"  when  the  light  is  suddenly  withdrawn.  This  last 
interesting  fact  would  seem  to  indicate  a  stimulation  process  of 
some  kind  in  the  retina  due  to  darkness — that  is,  withdrawal 
of  the  objective  stimulus.  Einthoven  and  Jolly*  have  applied 
the  sensitive  string  galvanometer  to  the  study  of  this  phenome- 
non. They  find  that  the  electrical  response  of  the  illuminated 
eye,  when  photographed,  presents  a  curve  of  much  complexity, 
and  they  conclude  that  its  complexity  is  due  to  the  fact  that 
several  different  processes  occur  together  in  the  stimulated 
retina.  They  offer  some  evidence  to  indicate  that  three  different 
processes  depending  on  the  reaction  of  three  different  substances 
may  be  distinguished.  These  substances  react  with  different 
velocities  and  with  different  changes  in  electric  potential  to 
flashes  of  light  and  "  flashes  of  darkness."  What  physiological 
effects  may  be  connected  with  these  three  processes  cannot 
yet  be  stated.  The  electrical  reaction  is  a  very  sensitive  one, 
lights  so  weak  as  to  be  near  the  threshold  for  the  human  eye 
give  a  distinct  electrical  change  in  the  frog's  retina,  and  an  eye 
that  has  been  kept  in  the  dark  for  some  time  (dark-adapted  eye) 
shows  an  increased  sensitiveness.  It  is  very  interesting,  also, 
to  find  that  the  frog's  retina  responds  to  a  range  of  light  vibrations 
that  corresponds  with  the  limits  of  the  visible  spectrum  as  seen 
by  the  human  eye.  If  the  electrical  response  is  a  true  indication 
of  functional  activity,  it  would  appear  that  the  frog's  vision  has 
about  the  same  extent  as  our  own  as  regards  the  ether  waves 
of  different  periods  of  vibration. 

The  Visual  Purple — Rhodopsin. — The  change  that  takes  place 
in  the  rods  and  cones  whereby  the  vibratory  energy  of  the  ether 
waves  is  converted  into  nerve  impulses  is  unknown.  It  has  been 
assumed  by  some  observers  that  the  light  waves  act  mechanically, 
the  wave  movements  setting  into  vibration  portions  of  the  external 
segments  of  the  rods  or  cones,  and  that  this  mechanical  movement 
forms  the  direct  excitant  of  the  nerve  impulses.!  The  general 
view,  however,  is  that  the  process  is  photochemical, — that  is,  the 
impact  of  the  ether  waves  sets  up  chemical  changes  in  the  rods  or 
cones  which  in  turn  give  rise  to  nerve  impulses  that  are  transmitted 
to  the  brain.  We  have  an  analogy  for  this  action  in  the  known 
change  produced  by  light  upon  sensitized  photographic  films.  In 
the  retina  itself  some  basis  for  such  a  view  is  found  in  the  existence 
of  a  red  pigment  which  is  bleached  by  light.  This  interesting  dis- 

*  Einthoven  and  Jolly,  "Quarterly  Journal  of  Experimental  Physiology,' 
1,  373,  1908.  _ 

t  Zenker,  "  Archiv  f.  mik.  Anatomic,"  3,  248,  1867. 


PROPERTIES    OF    THE    RETINA.  339 

covery  was  made  by  Boll,*  and  the  facts  were  afterward  carefully 
investigated  by  Kiihne.f  The  red  pigment,  known  usually  as 
visual  purple  or  rhodopsin,  is  found  only  in  the  external  segments 
of  the  rods;  the  cones  do  not  contain  it.  In  the  fovea,  therefore, 
which  has  only  cones,  the  pigment  is  entirely  absent.  The  existence 
of  the  visual  purple  may  be  demonstrated  very  easily.  A  frog  is 
kept  for  some  time  in  the  dark;  it  is  then  killed  and  an  eye  removed 
and  bisected  equatorially.  If  the  vitreous  is  removed  from  the  pos- 
terior half  the  retina  may  be  detached  by  means  of  a  pair  of  forceps. 
When  the  operation  is  performed  in  red  or  yellow  light,  as  in  photo- 
graphic work,  the  detached  retina  on  examination  by  daylight  i& 
found  to  be  a  deep-red  color;  but  after  a  short  exposure  it  fades 
rapidly,  finally  becoming  colorless.  If  the  frogs  before  operation 
were  exposed  to  strong  daylight,  the  retina  is  found  to  be 
colorless.  A  similar  pigment  is  found  in  the  eyes  of  man  and 
the  other  mammalia.  It  has  been  shown,  moreover,  that  a  photo- 
graph may  be  made  upon  the  surface  of  the  retina  by  means  of  this 
purple.  If  the  head  of  a  rabbit  or  frog  that  has  been  kept  in  the 
dark  for  some  time  is  exposed  with  proper  precautions  to  the  light 
of  a  window,  for  instance,  the  part  of  the  retina  on  which  the  image 
of  the  window-lights  falls  will  be  bleached,  while  the  parts  upon 
which  the  image  of  the  window-bars  falls  and  the  surrounding  areas 
of  the  retina  will  retain  their  red  color.  A  figure  of  such  a  retinal 
photograph  or  optogram,  as  it  is  called,  is  represented  in  the  accom- 
panying illustration  ( Fig.  142) .  The  visual  purple  has  been  extracted 
from  the  rods  by  solu- 
tions of  bile  salts,  this 
substance  having  the 
power  to  discharge  the 
pigment  from  its  com- 
bination in  the  rods 
in  the  same  way  as  it 
discharges  hemoglobin  t  2 

from   its    Combination  Fig    142._Optogram  in  eye  of  rabbit:   1,  The  nor- 

in  the   red   COrpUSCleS.       mal  appearance  of  the  retina  in  the  rabbit's  eye:  a,  The 

entrance  of  the  optic  nerve;    6,  6,  a  colorless  strip  of 

The       Solutions      thus       medullated  nerve  fibers;  c,  a  strip  of  deeper  color  sepa- 
i_,     •       j  rating  the  lighter  upper  from  the  more  heavily  pigmented 

Obtained         are         alSO       lower  portion.     2  shows  the  optogram  of  a  window. 

bleached  upon  ex- 
posure to  light.  We  have  in  the  visual  purple,  therefore,  an  un- 
stable substance  readily  decomposed  or  altered  by  the  mechanical 
effect  of  the  ether  waves,  and  also,  it  may  be  said,  by  gross  me- 
chanical reactions,  such  as  compression;  and  there  can  be  little 
doubt  that  the  substance  plays  an  important  part  in  the  functional 

*  Boll,  "Archiv  f.  Physiologic,"  1877,  4. 

t  Kiihne,  "Untersuch.  a.  d.  physiol.  Inst.  d.  Univ.  Heidelberg,"  vol.  i, 
1878.  Also  "The  Photochemistry  of  the  Retina,"  etc.,  translated  by  Foster, 
London,  1878. 


340  THE  SPECIAL  SENSES. 

response  of  the  rod  elements.  It  has  been  shown  that  provision 
exists  in  the  retina  for  the  constant  regeneration  of  this  red  pigment. 
It  will  be  remembered  that  the  external  segments  of  the  rods  im- 
pinge upon  the  heavily  pigmented  epithelial  cells  that  lie  between 
the  rods  and  the  choroid  coat.  From  experiments  upon  frogs'  eyes 
it  appears  that  a  portion  of  the  retina  detached  from  the  pigment 
cells  and  bleached  by  the  action  of  light  is  not  able  to  regenerate  its 
visual  purple  until  again  laid  back  upon  the  choroid  coat.  This 
regenerating  influence  of  the  black  pigmented  cells  may  be  con- 
nected with  another  interesting  relation  that  they  exhibit. '  Under 
normal  conditions  delicate  processes  extend  from  these  cells  and 
penetrate  between  the  rods  and  cones.  When  the  eye  is  exposed 
to  light  the  black  pigment  migrates  along  these  processes  as  far  even 
as  the  external  limiting  membrane,  and  it  is  possible  that  this  ar- 
rangement may  be  useful  in  obviating  diffuse  radiation  of  light 
from  one  rod  to  another.  When  the  eye  is  kept  in  the  dark,  however, 
the  pigment  moves  outwardly  and  collects  around  the  external 
segments,  where  the  process  of  regeneration  of  the  visual  purple  is 
taking  place.  Further  evidence  that  the  visual  purple  is  connected 
with  the  irritability  of  the  rods  toward  light  stimulation  is  shown 
by  the  fact  that  when  it  is  exposed  to  the  different  rays  of  the  spec- 
trum the  absorption  of  light  is  greatest  in  that  part  of  the  spec- 
trum (green)  which  appears  the  brightest  in  vision  when  carried  out 
under  such  conditions  as  may  be  supposed  to  involve  the  activity 
chiefly  of  the  rods  (see  below  for  these  conditions).  It  is,  however, 
perfectly  obvious  that  visual  purple  is  not  essential  to  vision.  The 
fact  that  it  is  absent  from  the  fovea  centralis  is  alone  sufficient 
proof  of  this  statement.  Moreover,  it  seems  to  be  absent  entirely 
in  the  eyes  of  some  animals;  for  instance,  the  pigeon,  hen,  some 
reptiles,  and  some  bats.  The  most  attractive  view  of  the  function 
of  the  visual  purple  is  that  it  serves  to  increase  the  delicacy  of  re- 
sponse or  irritability  of  the  rods  in  dim  lights, — a  view  that  is  ex- 
plained in  more  detail  in  the  paragraph  below,  dealing  with  the  sup- 
posed difference  in  function  between  the  rods  and  cones. 

The  Extent  of  the  Visual  Field — Perimetry. — By  the  visual  field 
of  each  eye  is  meant  the  entire  extent  of  the  external  world  which 
when  the  eye  is  fixed  forms  an  image  upon  or  is  projected  upon  the 
retina  of  that  eye.  From  what  has  been  said  previously  regarding 
the  dioptrics  of  the  eye  it  is  obvious  that  the  visual  field  is  inverted 
upon  the  retina,  and  that,  therefore,  objects  in  the  upper  visual  field 
fall  upon  the  lower  half  of  the  retina,  and  objects  in  the  right  half 
of  the  visual  field  fall  upon  the  left  half  of  the  retina.  Assuming 
that  the  retina  is  sensitive  to  light  up  to  the  ora  serrata,  it  is  evi- 
dent that  if  the  eye  were  protruded  sufficiently  from  its  orbit  its 
projected  visual  field  when  represented  upon  a  flat  surface  would 
have  the  form  of  a  circle,  the  center  of  which  would  correspond  to 


PROPERTIES    OF    THE    RETINA. 


341 


the  fovea  centralis.  As  a  matter  of  fact,  the  configuration  of  the 
face  is  such  as  to  cut  off  a  considerable  part  of  this  field,  in  any 
fixed  position  of  the  eyes,  and  to  give  to  the  field  as  it  actually 
exists  an  irregular  outline.  The  bridge  of  the  nose,  the  projecting 
eyebrows,  and  cheek  bones  serve  to  thus  limit  the  field;  and,  in 
addition,  the  sensitivity  of  the  peripheral  portion  of  the  retina 


Fig.  143. — Perimeter.  The  semicircular  bar  may  be  placed  in  any  meridian.  A 
given  object  is  then  mpved  along  the  bar  from  without  in  until  it  is  just  perceived.  The 
angular  distance  at  which  this  occurs  is  marked  off  on  the  corresponding  meridian  on  the 
chart  seen  a«,  the  left  of  the  figure.  The  eye  examined  gazes  over  the  top  of  the  vertical 
rod  at  the  right  at  a  fixed  point  in  the  middle  of  the  semicircular  bar. 

may  not  extend  equally  far  toward  the  ora  serrata  in  different 
eyes  or  in  different  meridians  of  the  same  eye.  To  obtain  the 
exact  outline  and  extent  of  the  visual  field  in  any  given  case  it 
is  only  necessary  to  keep  the  eye  fixed  and  then  to  move  a  small 
object  in  the  different  meridians  and  at  the  same  distance  from 
the  eye.  The  limits  of  vision  may  be  obtained  in  this  way  along 
each  meridian  and  the  results  combined  upon  an  appropriate 
chart.  An  instrument,  the  perimeter,  has  been  devised  to  facilitate 
the  process  of  charting  the  visual  field.  It  has  been  given  a  number 
of  different  forms,  one  of  which  is  illustrated  in  Fig  143.  The  shape 


342 


THE    SPECIAL    SENSES. 


of  the  visual  fields  in  the  normal  eye  is  represented  in  Fig.  144. 
The  determination  of  the  visual  fields  is  of  especial  importance  in 
cases  of  brain  lesions  involving  the  visual  area  in  the  occipital  lobe. 
The  extent  and  portion  of  the  retina  affected  may  be  used  to  aid  in 
locating  the  seat  of  the  lesion.  For  physiological  and  for  clinical 
purposes  it  is  necessary  to  distinguish  between  the  central  (or  direct) 
and  the  peripheral  (or  indirect)  fields  of  vision.  The  former  term 
is  meant  to  refer  to  that  portion  of  the  field  which  falls  upon  the 
fovea  centralis;  in  other  words,  it  is  the  projection,  in  any  fixed 
position  of  the  eye,  of  the  fovea  into  the  external  world.  The 
peripheral  field  refers  to  the  rest  of  the  visual  field  which  is  pro- 
jected upon  the  retina  outside  the  fovea.  As  a  matter  of  fact,  all 
of  our  distinct  and  most  useful  vision,  in  the  daytime  at  least,  is 
effected  through  the  fovea.  When  the  eye  is  kept  fixed,  the  small 
portion  of  the  external  world  that  falls  upon  the  fovea  is  seen  dis- 
tinctly. All  the  rest  is  seen  more  or  less  indistinctly  in  proportion 


061     081     OlA 


Fig.   144.  —  Perimeter  chart  to  show  the  field  of  vision  for  a  right  eye  when  kept  in  a  fixed 

position. 

to  the  distance  of  its  retinal  image  from  the  fovea.  In  using  our 
eyes,  therefore,  we  keep  them  continually  in  motion  so  as  to  bring 
each  object,  as  we  pay  especial  attention  to  it,  into  the  field  of 
central  vision.  The  line  from  the  fovea  to  the  point  looked  at  is 
designated  as  the  line  of  sight  or  visual  axis.  The  area  of  the  fovea 
is  quite  small.  The  measurements  given  by  different  observers 
vary  somewhat,  especially  as  in  some  cases  the  measurements  are 


PROPERTIES    OF    THE    RETINA.  343 

estimated  for  the  bottom  of  the  depression,  the  fundus,  and  in 
others  for  the  diameter  from  edge  to  edge.  The  average  diameter 
is  usually  given  as  lying  between  0.3  and  0.4  mm.  Lines  drawn 
from  the  ends  of  this  diameter  to  the  nodal  point  of  the  eye  sub- 
tend an  angle  of  1  degree  to  1.5  degrees;  and,  therefore,  all  objects 
in  the  external  world  around  the  line  of  sight  which  lie  within  this 
visual  angle  are  comprised  in  the  central  field  of  vision,  and  their 
retinal  images  fall  upon  the  fovea.  Unilateral  lesions-  of  one 
occipital  lobe  cause  half -blindness  (hemianopia)  in  the  retinas  on  the 
same  side, — that  is,  lesions  in  the  right  occipital  lobe  cause  blind- 
ness of  the  right  halves  of  the  retinas,  while  injuries  to  the  left 
occipital  lobes  are  accompanied  by  loss  of  vision  on  the  left  sides 
of  the  retinas  (see  p.  207) ;'  but  such  unilateral  lesions,  it  is  stated, 
do  not  involve  the  central  field  of  vision — only  the  peripheral 
portion  of  the  field  is  affected.  In  connection  with  its  special 
functions  in  vision  the  fovea  centralis  possesses  a  peculiar  struc- 
ture. It  forms  a  shallow  depression  in  the  center  of  the  retina 
described  by  some  authors  as  elliptical,  by  others  as  circular  in  out- 
line. In  the  center  of  the  fovea  lies  a  smaller,  very  shallow  depres- 
sion spoken  of  as  the  foveola.  The  diameter  of  the  fovea,  as  stated 
above,  is  estimated  differently  by  different  authors.  While  meas- 
urements on  preserved  specimens  give  the  diameter  as  0.2  to 
0.4  mm.,  ophthalmoscopic  examination  seems  to  indicate  that  in 
the  fresh  state  it  may  be  larger.  According  to  Fritsch,*  the  fundus, 
reckoned  from  the  point  at  which  the  depression  begins,  has  a  diam- 
eter of  0.5  to  0.75  mm.  Within  the  fovea  cones  only  are  present, 
and  these  cones  are  longer  and  more  slender  (diameter,  0.002  mm.) 
than  in  the  rest  of  the  retina.  Moreover,  the  thickness  of  the  retina 
is  much  reduced  in  the  fovea,  whence  arises  the  depression.  At 
this  point  the  cones  are  practically  exposed  directly  to  the  light, 
whereas  in  other  parts  the  light  must  penetrate  the  other  layers 
before  reaching  the  rods  and  cones.  Lying  around  the  fovea  is  an 
area  about  6  mm.  in  diameter,  of  a  yellowish  color,  and  hence 
known  as  the  macula  lutea.  The  portion  of  the  visual  field  falling 
upon  this  area,  in  a  fixed  position  of  the  eye,  is  sometimes  called  the 
macular  field.  According  to  some  observers  f  the  yellow  color  of 
the  macula  is  due  to  post-mortem  changes. 

Visual  Acuity. — The  distinctness  of  vision  or  the  resolving 
power  of  the  eye  varies  greatly  in  different  parts  of  the  retina. 
It  may  be  measured  for  the  fovea  by  bringing  two  fine  lines  closer 
and  closer  together  until  the  eye  is  unable  to  see  them  as  two  dis- 
tinct objects.  Measured  in  this  way,  it  is  usually  stated  that  when 
the  distance  between  the  lines  subtends  an  angle  of  1  minute 
(60  seconds)  at  the  eye,  the  limit  of  resolvability  is  reached.  This 

*  Fritsch,  " Sitzungsberichte  d.  konig.  Akad.  d.  Wiss.,"  Berlin,  1900. 
tSiven,  " Skandinavisches  Archiv  f.  Physiol.,"  1905,  17,  306. 


344 


THE    SPECIAL    SENSES. 


angle  on  the  retina  comprises  an  area  of  about  0.004  mm.  in  diam- 
eter, sufficient  to  cover  two  cones  in  the  fovea.  A  simpler  method 
to  ascertain  the  size  of  a  just  perceptible  image  on  the  retina  is  to 
use  a  black  spot  upon  a  white  background.  At  a  sufficient  dis- 
tance this  object  will  be  invisible,  the  white  margins  separated 
by  the  diameter  of  the  black  spot  fuse  together,  but  if  brought 
closer  to  the  eye,  the  spot  will  be  just  distinguishable  at  a  certain 
distance.  The  diameter  of  the  spot  being  known,  and  its  distance 
from  the  eye,  the  size  of  the  retinal  image  may  be  calculated. 
Using  this  method,  Guillery*  estimated  the  diameter  of  the  just 
perceptible  retinal  image,  or,  as  it  has  been  appropriately  called, 
the  physiological  point,  at  0.0035  mm.  These  estimates  apply  only 
to  the  fovea,  and,  indeed,  to  the  central  part  of  the  fovea,  the 
foveola.  Numerous  authors  have  called  attention  to  the  fact  that 


?°   3<f  10°  £*  o°  &  if  W *P 

Fig.  145. — Curve  to  show  the  relative  acuity  of  vision  in  the  central  and  peripheral  fields 
and  in  the  light-adapted  and  the  dark-adapted  eye. — (Koester.)  The  full  line  represents 
the  relative  acuteness  of  vision  in  the  eye  exposed  to  usual  illumination.  From  the  center  of 
the  fovea,  0°,  the  acuity  of  vision  falls  rapidly  at  first  and  then  more  slowly  as  one  passes  out- 
ward into  the  peripheral  field.  The  dotted  line  represents  the  acuity  of  vision  in  dim  lights. 
The  fovea,  under  this  latter  condition,  is  less  sensitive  than  the  parts  of  the  retina  at  an  angular 
distance  of  10°  or  even  69°. 

visual  acuity,  as  measured  by  the  least  distance  at  which  two  ob- 
jects may  be  seen  separately,  varies  with  the  intensity  of  illumina- 

*  Guillery,  "Zeitschrift  f.  Psychologie  u.  Physiol.  d.  Sinnesorgane,"  12, 
243,  1896. 


PROPERTIES    OF    THE    RETINA.  345 

tion.  The  estimates  given  are  for 'ordinary  room  light.  Out-of- 
doors,  and  especially  in  the  case  of  persons  who  live  habitually 
an  outdoor  life,  visual  acuity  or  the  power  of  visual  discrimination 
is  increased.  We  may  believe  that  under  the  most  favorable  con- 
ditions of  illumination  and  contrast  we  can  resolve  two  objects 
whose  images  on  the  fovea  are  separated  by  a  distance  about  equal 
to  the  diameter  (0.002  mm.)  of  a  single  cone.  The  acuity  of  vision 
does  not  vary  greatly  throughout  the  fovea;  any  object  whose 
retinal  image  falls  well  within  the  fovea  can  be  seen  quite  dis- 
tinctly in  all  of  its  parts  when  the  eye  is  fixed  for  the  center  of  the 
Object.  This  is  the  case,  for  instance,  with  the  moon.  Neverthe- 
less, in  looking  at  such  an  object  as  the  moon  the  eye,  to  make  out 
details,  will  fixate  one  point  after  another,  showing  that  for  most 
distinct  vision  we  use  probably  only  the  center  of  the  fovea.  As 
we  pass  out  from  the  fovea  into  the  peripheral  field  of  vision  the 
acuity  of  vision  diminishes  very  rapidly,  so  that  at  20  degrees,  for 
instance,  from  the  center  of  the  fovea  the  retinal  images  must  be 
separated  by  a  distance  of  0.035  mm.  in  order  to  be  recognized 
as  distinct;  a  distance  ten  times  as  great  as  is  necessary  in  the 
fovea.  On  this  account  our  vision  in  the  peripheral  field  is  very 
indistinct, — details  of  form  cannot  be  clearly  perceived.  The 
rapidity  with  which  visual  acuity  diminishes  as  we  pass  outward 
from  the  fovea  is  indicated  by  the  curve  given  in  Fig.  145.  In  all 
close  work,  therefore,  we  keep  our  eyes  moving  continually  so  as  to 
bring  one  point  after  another  into  the  center  of  the  fovea,  as  is  well 
illustrated  by  the  act  of  reading.  If  the  eye  is  kept  fixed  upon  the 
central  letter  of  a  long  word,  only  one  or  two  letters  on  each  side 
can  be  made  out  distinctly  in  spite  of  the  fact  that  with  such 
familiar  objects  we  can  guess  the  letter  even  when  the  image  is  not 
entirely  distinct.  In  ophthalmological  practice  the  acuity  of  vision 
(central  vision)  is  measured  usually  by  test  letters  whose  size  is 
such  that  at  the  distance  at  which  they  are  read — say,  6  meters  (20 
feet),  the  practical  far  point  at  which  no  accommodation  is  needed — 
each  subtends  at  the  eye  an  angle  of  5  minutes.  An  eye  that  can 
distinguish  the  letters  at  this  distance  is  said  to  be  normal;  one  that 
can  distinguish  them  only  at  a  smaller  distance  or  at  the  given 
distance  requires  letters  of  larger  size  has  a  subnormal  acuity  of 
vision.  If,  for  instance,  an  individual  at  20  feet  can  read  only 
those  letters  that  the  normal  eye  can  distinguish  at  100  feet  his 
visual  acuity,  V,  is  equal  to  -ffa. 

Relation  between  the  Amount  of  Sensation  and  the  Intensity 
of  the  Stimulus — Threshold  Stimulus. — With  the  sensory  as  with 
the  motor  nerves  we  may  distinguish  between  various  degrees  of  sub- 
maximal  stimulation.  The  stronger  the  stimulus,  the  stronger  the 
reaction, — that  is,  in  the  case  of  the  optic  nerve,  the  visual  sensation. 


346  THE  SPECIAL  SENSES. 

The  end  reaction  of  the  activity  of  a  sensory  nerve  is  a  state  of  con- 
sciousness. The  variations  in  magnitude  of  this  state  can  not  be 
measured  with  objective  exactness,  they  must  be  judged  subjectively 
by  the  individual  concerned.  A  stimulus  too  weak  to  give  a  re- 
sponse with  a  motor  nerve  is  usually  designated  in  physiology  as 
subminimal;  a  similar  stimulus  with  sensory  nerves  is  frequently 
expressed  by  the  equivalent  term  subliminal, — that  is,  below  the 
threshold.  So  a  stimulus  just  strong  enough  to  provoke  a  percep- 
tible reaction  is  the  minimal  stimulus  for  efferent  nerves  and  the 
threshold  stimulus  for  sensory  nerves.  Inasmuch  as  the  variations 
in  the  intensity  of  consciousness  can  not  be  adequately  measured, 
it  is  customary,  in  studying  the  relations  of  the  strength  of  stimulus 
to  the  conscious  response,  to  pay  attention  to  the  strength  of  stimu- 
lus under  any  given  condition  which  is  sufficient  to  arouse  a  just 
perceptible  difference  in  the  conscious  reaction.  Proceeding  upon 
this  method,  it  is  found  in  the  case  of  the  visual  sensations  and  the 
optic  nerve,  as  with  other  sensations  and  their  corresponding  nerves, 
that  the  increase  of  stimulus  necessary  to  cause  a  just  perceptible 
change  in  consciousness  varies  with  the  amount  of  stimulus  already 
acting.  If,  for  instance,  the  retina  is  being  stimulated  by  a  light  of 
1  candle  power  an  increase  of  illumination  to  1.1  candle  power  may 
make  a  perceptible  difference  in  sensation.  But  if  the  retina  is 
being  illuminated  by  a  light  of  10  candle  power  an  increase  to  10.1 
candle  power  would  probably  make  no  perceptible  difference.  For 
a  certain  range  of  stimulation,  in  fact,  it  has  been  stated  that  the 
increase  in  stimulus  must  be  a  constant  fractional  part  of  the  stimu- 
lus already  acting.  That  is,  in  the  hypothetical  case  given,  if,  with 
1  candle  power,  an  increase  to  1.1  candle  power  makes  a  just  per- 
ceptible difference  in  consciousness,  then  with  10  candle  power  an 
increase  of  -£$  of  the  acting  stimulus,  namely — 1  candle  power — will 
be  necessary  to  cause  a  perceptible  difference.  The  relation  as 
expressed  in  this  form  is  known  as  Weber's  law ;  but  it  seems  prob- 
able that,  while  the  general  fact  is  true,  this  exact  expression  of  it 
holds  only  approximately  for  an  intermediate  range  of  stimulation. 
In  this  matter  of  a  threshold  stimulus  the  sensitiveness  of  the 
retina  shows  also  certain  interesting  differences  in  the  foveal  as 
compared  with  the  peripheral  field.  The  difference  is  especially 
marked  when  the  reaction  of  the  retina  in  strong  lights  is  compared 
with  its  reaction  in  dim  lights. 

The  Light-adapted  and  the  Dark-adapted  Eye.— The  con- 
dition of  the  retina  changes  when  after  exposure  to  light  it  is  sub- 
mitted to  darkness,  the  change  being  most  marked  in  the  peripheral 
field.  When  one  passes  from  daylight  into  a  dark  room  vision 
at  first  is  very  imperfect,  but  after  some  minutes  it  rapidly  im- 
proves, "as  the  eye  becomes  accustomed  to  the  dark."  The 


PROPERTIES    OF    THE    RETINA.  347 

change  is  known  as  an  adaptation,  and  in  this  respect  the  retina 
differs  from  the  sensitive  photographic  plate.  Comparison  of  the 
threshold  stimulus  for  different  parts  of  the  retina,  in  an  eye 
exposed  alternately  to  darkness  and  to  light,  has  shown  that 
in  the  dark  the  sensitiveness  in  the  peripheral  field  increases 
greatly  during  an  hour  or  so,  while  that  of  the  foveal  field  is  appar- 
ently unchanged.  With  such  a  dark-adapted  eye,  therefore, 
there  will  be  a  certain  dim  light  which  will  be  seen  by  the  per- 
ipheral parts  of  the  retina,  but  perhaps  will  cause  no  reaction 
upon  the  fovea.  For  such  a  degree  of  light,  therefore,  the  fovea 
would  be  blind.  This  general  fact  has,  indeed,  long  been  known. 
Anyone  may  notice  in  late  twilight,  when  the  stars  are  beginning 
to  appear,  that  a  very  faint  star  may  disappear  when  looked  at, — that 
is,  when  its  image  is  brought  upon  the  fovea ;  to  see  it  one  must  direct 
his  eyes  a  little  to  the  side,  so  as  to  bring  its  image  into  the  periph- 
eral field.  This  greater  sensitiveness  of  the  dark-adapted  eye  in 
the  peripheral  field  where  the  rods  predominate  over  the  cones  seems 
to  be  associated  with  the  movement  of  the  pigment  in  the  pigment 
epithelium  (see  above)  and  the  resulting  regeneration  of  the  visual 
purple  in  the  external  segments  of  the  rods.  The  increase  in  the 
visual  purple  in  the  dark  may,  indeed,  account  for  the  increased 
sensitiveness  to  light  in  the  rod-region  and  explain  why  a  similar 
increase  fails  to  occur  in  the  fovea,  where  only  cones  are  present. 
The  curve  given  in  Fig.  145  shows  that  in  the  dark-adapted  eye 
the  threshold  of  vision  in  the  peripheral  field  may  be  lower  than  in 
the  fovea.  In  accordance  with  these  facts  von  Kries*  has  suggested 
that  the  rods,  the  peripheral  field  of  the  retina,  are  especially 
adapted  for  vision  in  dim  lights,  night  vision,  while  the  cones  are 
especially  adapted  for  vision  in  strong  lights,  day  vision.  This 
general  fact  will  perhaps  accord  with  the  experience  of  anyone  who 
attempts  to  estimate  the  value  of  his  peripheral  vision  in  dim 
nightlight  as  compared  with  daylight.  Other  interesting  differ- 
ences in  the  reaction  of  the  light-adapted  and  the  dark-adapted 
eye  are  referred  to  below  in  connection  with  color  blindness. 

CHARACTERISTICS  OF  THE  VISUAL  SENSATIONS. 

In  addition  to  the  spatial  attributes  connected  with  our  visual 
sensations — that  is,  the  perception  of  form — they  are  characterized 
by  two  properties  which  may  be  described  in  general  as  variations 
in  intensity  and  in  quality. 

Luminosity  or  Brightness. — That  characteristic  which  we 
describe  as  the  luminosity  or  brightness  of  a  visual  sensation  has 

*  Von  Kries,  "  Zeitschrift  f .  Psychologic  u.  Physiologic  d.  Sinnesorgane,* 
9.  81,  1895. 


348 


THE    SPECIAL    SENSES. 


been  defined  differently  by  various  writers.  We  may  consider  it, 
however,  as  the  expression  of  the  intensity  of  the  acting  stimulus. 
Sensations  of  the  same  quality  are  easily  compared  as  regards  their 
brightness.  We  can  tell  as  between  two  whites  or  two  greens  which 
is  the  brighter  of  the  two,  but  when  two  different  qualities — a  red 
and  a  green  sensation,  for  instance — are  compared  our  subjective 
determination  of  the  relative  brightness  is,  for  most  persons,  difficult 
or  impossible  to  make.  To  a  lesser  degree  the  difficulty  is  similar 
to  that  of  the  comparison  of  sight  and  sound.  According  to  the 
conception  adopted  here,  however,  that  the  brightness  is  an  ex- 
pression of  the  intensity  of  the  stimulus,  an  objective  standard  of 
comparison  might  be  obtained  by  measuring  the  resulting  action  cur- 
rents in  the  optic  nerve  fibers.  When  the  spectral  colors  are  ex- 
amined it  is  obvious  that  some  of  the  colors  are  brighter  than  others, 
the  extreme  red  and  extreme  violet,  for  instance,  possessing  little 
luminosity  as  compared  v/ith  the  yellow.  The  relative  brightness 


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Fig.  146. — Diagram  showing  the  distribution  of  the  intensity  of  the  spectrum  as  de- 
pendent upon  the  degree  of  illumination.  The  spectrum  is  represented  along  the  abscissa, 
the  numerals  giving  the  wave  lengths  from  red,  670,  to  violet,  430.  The  ordinates  give 
the  luminosity  of  the  different  colors.  Eight  curves  are  given  to  show  the  changes  in 
distribution  of  relative  brightness  with  changes  in  degree  of  illumination.  With  the 
greatest  illumination  the  maximum  brightness  is  in  the  yellow  (605-625) ;  with  weaker 
illumination  it  shifts  to  the  green  (535) .— (Kdnig.  ) 

of  the  different  spectral  colors  is  found  to  vary  with  the  amount  of 
illumination,  as  shown  in  the  curves  given  in  Fig.  146.     With  a 


PROPERTIES    OF    THE    RETINA.  349 

brilliant  spectrum  the  maximum  brightness  is  in  the  yellow,  but 
with  a  feeble  illumination  it  shifts  to  the  green.  This  fact  accords 
with  what  is  known  as  the  "  Purkinje  phenomenon/' — namely,  the 
changing  luminosity  and  color  value  of  colors  in  dim  lights.  As  the 
light  becomes  more  feeble  the  colors  toward  the  red  end  of  the 
spectrum  lose  their  quality,  the  blue  colors  being  perceived  last  of 
all,  just  as  in  late  twilight  it  may  be  noticed  that  the  sky  remains 
distinctly  blue  after  the  colors  of  the  landscape  become  indistin- 
guishable. It  should  be  added  that  the  "  Purkinje  phenomenon  " 
is  true  only  for  the  parts  of  the  retina  lying  outside  the  fovea, 
that  is,  for  the  peripheral  field.  As  the  light  grows  dimmer  the 
perception  of  blue  is  lost  first  in  the  fovea,  so  that  with  a  certain 
feebleness  of  illumination  the  central  field  becomes  blue-blind. 
With  a  very  feeble  illumination  the  dark-adapted  eye  becomes 
practically  totally  color  blind. 

Qualities  of  Visual  Sensations. — The  different  qualities  of  our 
color  sensations  may  be  arranged  in  two  series:  an  achromatic 
series,  consisting  of  white  and  black  and  the  intermediate  grays, 
and  a  chromatic  series,  comprising  the  various  spectral  colors, 
together  with  the  purples  made  by  combination  of  the  two  ends 
of  the  spectrum,  red  and  blue,  and  the  colors  obtained  by  fusion  of 
the  spectral  colors  with  white  or  with  black,  such,  for  instance,  as 
the  olives  and  browns. 

The  Achromatic  Series. — Our  standard  white  sensation  is  that 
caused  by  sunlight.  Objects  reflecting  to  our  eye  all  the  visible 
rays  of  the  sunlight  give  us  a  white  sensation.  This  sensation, 
therefore,  is  due  primarily  to  the  combined  action  of  all  the  visible 
rays  of  the  spectrum,  each  of  which,  taken  separately,  would  give 
us  a  color  sensation.  White  or  gray  may  be  produced  also  by  the 
combined  action  of  certain  pairs  of  colors, — complementary  colors, — 
as  is  described  below.  Black,  on  the  contrary,  is  the  sensation 
caused  by  withdrawal  of  light.  It  must  be  emphasized  that  in 
order  to  see  black  a  retina  must  be  present.  It  is  probable  that 
a  person  with  both  eyes  enucleated  has  no  sensation  of  darkness. 
That  black  is  a  sensation  referable  to  a  condition  of  the  retina  is 
made  probable  also  by  the  interesting  observations  recorded  by 
Gotch,* — namely,  that  when  an  eye  that  has  been  exposed  to  light 
is  suddenly  cut  off  from  the  light  there  is  an  electrical  change  in  the 
retina,  a  dark  response,  similar  to  that  caused  by  throwing  light  on 
a  retina  previously  kept  in  the  dark.  Blackness,  therefore,  is  a 
sensation  produced  by  withdrawing  light  from  the  retina,  and  a 
black  object  is  one  that  reflects  no  light  to  the  eye.  Black  may  be 
combined  with  white  to  produce  the  series  of  grays,  and  when  com- 
bined with  the  spectral  colors  it  gives  a  series  of  modified  color  tones, 

*  Gotch,  "  Journal  of  Physiology,"  29,  388,  1903. 


350  THE    SPECIAL    SENSES. 

thus  the  olives  of  different  shades  may  be  considered  as  combina- 
tions of  green  and  black  in  varying  proportions. 

The  chromatic  series  consists  of  those  qualities  to  which  we  give 
the  name  of  colors,  and,  as  stated  above,  they  comprse  the  spectral 
colors,  and  the  extraspectral  color,  purple,  together  with  the  light- 
weak  and  light-strong  hues  obtained  by  combining  the  colors  with 
white  or  black.  In  the  spectrum  many  different  colors  may  be 
detected, — some  observers  record  as  many  as  one  hundred  and 
sixty, — but  in  general  we  give  specific  names  only  to  those  that 
stand  sufficiently  far  apart  to  represent  quite  distinct  sensations, — 
namely,  the  red,  orange,  yellow,  green,  blue,  and  violet.  When 
light  is  taken  from  a  definite  limited  portion  of  the  spectrum  we 
have  a  monochromatic  light  that  gives  us  a  distinct  color  sensation 
varying  with  the  wave  length  of  the  portion  chosen. 

Color  Saturation  and  Color  Fusion. — The  term  saturation  as 
applied  to  colors  is  meant  to  define  their  freedom  from  accompany- 
ing white  sensation.  A  perfectly  saturated  color  would  be  one 
entirely  free  from  mixture  with  white.  On  the  objective  side  it  is 
easy  to  select  a  monochromatic  bundle  of  rays  from  the  spectrum 
without  admixture  of  white  light,  but  on  the  physiological  side  it  is 
not  probable  that  the  color  sensation  thus  produced  is  entirely  free 
from  white  sensation,  since  the  monochromatic  rays  may  initiate 
in  the  retina  not  only  the  specific  processes  underlying  the  pro- 
duction of  its  special  color,  but  at  the  same  time  give  rise  in  some 
degree  to  the  processes  causing  white  sensations.  Even  the  spectral 
colors  are  therefore  not  entirely  saturated,  but  they  come  as  near 
to  giving  us  this  condition  as  we  can  get  without  changing  the  state 
of  the  retina  itself  by  previous  stimulation. 

Color  Fusion. — By  color  fusion  we  mean  the  combination  of  two 
or  more  color  processes  in  the  retina,  this  end  being  obtained  by 
superposing  upon  the  same  portion  of  the  retina  the  rays  giving 
rise  to  these  color  processes.  It  must  be  borne  in  mind  that  color 
fusion  upon  the  retina  is  quite  a  different  tning  from  color  mixture 
as  practised  by  the  artist.  A  blue  pigment,  such  as  Prussian  blue, 
for  instance,  owes  its  blue  color  to  the  fact  that  when  sunlight  falls 
upon  it  the  red-yellow  rays  are  absorbed  and  only  the  blue,  with 
some  of  the  green,  rays  are  reflected  to  the  eye.  So  a  yellow  pig- 
ment, chrome  yellow,  absorbs  the  blue,  violet,  and  red  rays  and 
reflects  to  the  eye  only  the  yellow  with  some  of  the  green  rays.  A 
mixture  of  the  two  upon  the  palette  will  absorb  all  the  rays  except 
the  green  and  will  therefore  appear  green  to  the  eye.  If,  however, 
by  means  of  a  suitable  device,  we  throw  simultaneously  upon  the 
retina  a  blue  and  a  yellow  light,  the  result  of  the  retinal  fusion  is 
a  sensation  of  white.  Many  different  methods  have  been  employed 
to  throw  colors  simultaneously  upon  the  retina,  the  most  perfect 


PROPERTIES    OF    THE    RETINA.  351 

being  a  system  of  lenses  or  mirrors  by  which  different  portions  of 
a  spectrum  can  be  superposed.  The  usual  device  employed  in 
laboratory  experiments  is  that  of  rotation  of  discs  of  colored  paper. 
Each  disc  has  a  slit  in  it  from  center  to  periphery  so  that  two  discs 
can  be  fitted  together  to  expose  more  or  less  of  each  color.  If  a 
combination  of  this  kind  is  attached  to  a  small  electrical  motor  it 
can  be  rotated  so  rapidly  that  the  impressions  of  the  two  colors 
upon  the  retina  follow  at  such  a  short  interval  of  time  as  to  be  prac- 
tically simultaneous. 

The  Fundamental  Colors. — By  the  methods  of  color  fusion 
it  can  be  shown  that  three  colors  may  be  selected  from  the  spec- 
trum whose  combinations  in  different  proportions  will  give  white, 
or  any  of  the  intermediate  color  shades,  or  purple  Considered 
purely  objectively,  a  set  of  three  such  colors  may  be  designated 
as  the  fundamental  colors,  and  red,  yellow,  and  blue,  or  red, 
green,  and  violet  have  been  the  three  colors  selected.  On  the 
physiological  side,  however,  it  has  been  assumed  that  there  are 
certain  more  or  less  independent  color  processes — photochemical 
processes — in  the  retina  which  give  us  our  fundamental  color  sen- 
sations, and  that  all  other  color  sensations  are  combinations  of  these 
processes  in  varying  proportions  with  each  other  or  with  the  proc- 
esses causing  white  and  black.  Referring  only  to  the  colors  proper, 
the  fundamental  color  sensations  according  to  some  views  are  red, 
green,  and  blue  or  violet;  according  to  others,  they  are  red,  yellow, 
green,  and  blue.  (See  paragraph  on  Theories  of  Color  Vision.) 

Helmholtz  calls  attention  to  the  fact  that  the  names  used  for  these  funda- 
mental color  sensations  are  obviously  of  ancient  origin,  thus  indicating  that 
the  difference  in  quality  of  the  sensations  has  been  long  recognized.  Red  is 
from  the  Sanskrit  rudhira,  blood;  blue  from  the  same  root  as  blow,  and  re- 
fers to  the  color  of  the  air;  green  from  the  same  root  as  grow,  referring  to  the 
color  of  vegetation.  Yellow  seems  to  be  derived  from  the  same  root  as  gold, 
which  typified  the  color.  The  other  less  distinct  qualities  have  names  of 
recent  application,  such  as  orange,  violet,  indigo  blue,  etc. 

Complementary  Colors. — It  has  been  found  by  the  methods  of 
color  fusion  that  certain  pairs  of  colors  when  combined  give  a  white 
(gray)  sensation.     It  may  be  said,  in  fact,  that  for  any  given  color 
there  exists  a  complement  such  that  the  fusion  of  the  two  in  suitable 
proportions  gives  white.     If  we  confine  ourselves  to  the  spectral 
colors  we  recognize  such  complementary  pairs  as  the  following: 
Red  and  greenish  blue. 
Orange  and  cyan  blue. 
Yellow  and  indigo  blue. 
Greenish  yellow  and  violet. 

The  complementary  color  for  green  is  the  extraspectral  purple, 
Colors  that  are  closer  together  in  the  spectral  series  than  the 


352  THE    SPECIAL    SENSES. 

complementaries  give  on  fusion  some  intermediate  color  which  is 
more  saturated — that  is,  less  mixed  with  white  sensation — the  nearer 
the  colors  are  together.  Thus,  red  and  yellow,  when  fused,  give 
orange.  Colors  farther  apart  than  the  distance  of  the  comple- 
mefitaries  give  some  shade  of  purple.  On  the  physical  side,  there- 
fore, we  can  produce  a  sensation  of  white  in  two  ways:  Either  by  the 
combined  action  of  all  the  visible  rays  of  the  spectrum  (sunlight) 
or  by  the  combined  action  of  pairs  of  colors  whose  wave  lengths  vary 
by  a  certain  interval.  It  is  probable  that  in  the  retina  the  processes 
induced  by  these  two  methods  are  qualitatively  the  same,  the 
wave-lengths  represented  by  the  complementary  colors  setting  up 
by  their  combined  action  the  same  photochemical  processes  that 
normally  are  induced  by  the  sunlight. 

After-images. — As  the  name  implies,  this  term  refers  to  images 
that  remain  in  consciousness  after  the  objective  stimulus  has  ceased 
to  act  upon  the  retina.  They  are  due  doubtless  to  the  fact  that  the 
changes  set  up  in  the  retina  by  the  visual  stimulus  continue,  with 
or  without  modification,  after  the  stimulus  is  withdrawn.  After- 
images are  of  two  kinds:  positive  and  negative.  In  the  positive 
after-images  the  visual  sensation  retains  its  normal  colors.  If  one 
looks  at  an  incandescent  electric  light  for  a  few  seconds  and  then 
closes  his  eyes  he  continues  to  see  the  luminous  object  for  a  con- 
siderable time  in  its  normal  colors.  Objects  of  much  less  inten- 
sity of  illumination  may  give  positive  after-images,  especialy 
when  the  eyes  have  been  kept  closed  for  some  time,  as,  for 
instance,  upon  waking  in  the  morning.  In  negative  after- 
images the  colors  are  all  reversed — that  is,  they  take  on  the 
complementary  qualities  (see  Fig.  147).  White  becomes  black, 
red,  a  bluish  green,  and  vice  versa.  Negative  after-images 
are  produced  very  easily  by  fixing  the  eyes  steadily  upon  a 
given  object  for  an  interval  of  twenty  seconds  or  more  and 
then  closing  them.  In  the  case  of  colored  objects  the  after- 
image is  shown  better,  perhaps,  by  turning  the  eyes  upon  a 
white  surface  after  the  period  of  fixation  is  over.  After-images 
produced  in  this  way  often  appear  and  disappear  a  number  of 
times  before  ceasing  entirely,  and,  although  the  color  at  first  is  the 
complementary  of  that  of  the  object  looked  at,  it  may  change  before 
its  final  disappearance.  Anyone  who  has  gazed  for  even  a  brief 
interval  at  the  setting  sun  will  remember  the  number  of  colored  and 
changing  after-images  seen  for  a  time  when  the  eye  is  turned  to 
another  portion  of  the  sky.  That  several  different  after-images 
are  seen  in  this  case  is  due  to  the  fact  that  the  eyes  are  not  kept 
fixed  under  the  dazzling  light  of  the  sun,  and  a  number  of  different 
images  are  formed,  therefore,  upon  the  retina. 


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PROPERTIES   OF   THE   RETINA.  353 

After-images  may  be  used  in  a  very  instructive  way  to  show  that 
our  estimates  of  the  size  of  a  retinal  image  vary  with  the  distance  to 
which  we  project  it, — that  is,  with  the  distance  at  which  we  suppose 
we  see  it.  Once  the  image  is,  so  to  speak,  branded  on  the  retina, 
its  actual  size,  of  course,  does  not  vary,  but  our  judgment  of  its  size 
may  be  made  to  vary  rapidly  by  projecting  the  image  upon  screens  at 
different  distances.  If,  for  instance,  in  obtaining  the  after-image 
of  the  strips  shown  in  Fig.  147  one  moves  the  white  paper  used 
to  catch  the  image  toward  and  away  from  the  eye,  the  apparent  size 
varies  proportionally  to  its  distance. 

Color  Contrasts. — By  color  contrast  is  meant  the  influence 
that  one  color  field  has  upon  a  contiguous  one.  If,  for  instance,  a 
piece  of  blue  paper  is  laid  upon  a  larger  yellow  square,  the  color 
of  each  of  them  is  heightened  by  contrast.  A  piece  of  blue 
paper  on  a  blue  background  does  not  appear  so  saturated  as  when 
placed  against  a  yellow  background.  The  influences  of  contrast 
may  be  shown  in  a  great  variety  of  ways.*  For  instance,  if  a  disc 
like  that  in  the  illustration,  Fig.  149A,  is  rotated  rapidly,  it  should 
give  circles  of  gray, the  darkest  at  the  middle;  but  each  circle  should 
be  uniform  as  it  is  made  by  the  fusion  of  a  definite  amount  of  white 
and  black.  On  the  contrary,  the  appearance  obtained  is  that  repre 


Fig.    1494.— Black  and  white  disc  for  ex-        Fig.  149£.— Showing  the  result  when  the 
periment  on  contrast. — (Rood.)  disc  A  is  set  into  rapid  rotation. — (flood.) 

sented  in  Fig.  1495.  Each  circle  appears  darker  on  its  outer  edge 
where  it  borders  on  a  lighter  circle,  and  lighter  on  its  inner  edge  where 
it  borders  on  a  darker  circle.  Similar  contrasts  may  be  obtained  from 
comparing  shadows  cast  by  yellow  and  white  light.  If  a  rod  be 
arranged  in  a  dark  room  so  as  to  cast  a  shadow  from  an  opening 
admitting  daylight  and  one  also  from  a  lighted  candle,  either  shadow 
taken  separately  appears  black,  but  if  the  two  are  cast  side  by  side 
one  will  appear  blue,  the  other  yellow.  The  shadow  cast  by  the 
daylight,  being  illuminated  by  the  yellow  candle-light,  will  appear 
yellow,  and  the  other  shadow,  that  from  the  candle-light,  will  by 

*  Rood,  "Modern  Chromatics,"  "  International  Scientific  Series." 
23 


354  THE    SPECIAL    SENSES. 

contrast  seem  quite  blue.  A  striking  instance  of  the  effect  of  con- 
trast is  given,  also,  by  the  simple  experiment  of  Mayer,  illustrated 
in  Fig.  148.  The  gray  square  on  the  green  background  suffers  no 
apparent  change  from  contrast,  but  if  the  figure  is  covered  by  a 
sheet  of  white  tissue  paper  the  gray  square  at  once  takes  on  a  red- 
dish hue.  It  is  evident  that  in  all  artistic  and  ornamental  employ- 
ment of  colors  this  influence  must  be  considered,  and  empirical 
rules  are  established  which  indicate  for  the  normal  eye  the  bene- 
ficial or  the  killing  effect  of  different  colors  when  brought  into 
juxtaposition. 

Color  Blindness. — The  fact  that  some  eyes  do  not  possess 
normal  color  vision  does  not  seem  to  have  attracted  the  attention 
of  scientific  observers  until  it  was  studied  with  some  care  by  Dalton, 
the  distinguished  English  chemist,  at  the  end  of  the  eighteenth 
century.  Dalton  himself  suffered  from  color  blindness,  and  the 
particular  variety  exhibited  by  him  was  for  some  time  described 
as  Daltonism,  but  is  now  usually  designated  as  red  blindness.  The 
subject  was  given  practical  importance  by  later  observers,  espe- 
cially by  the  Swedish  physiologist  Holmgren,*  who  emphasized  its 
relations  to  possible  accidents  by  rail  or  at  sea  in  connection  with 
colored  signals.  It  is  now  the  practice  in  all  civilized  countries  to 
require  tests  for  color  blindness  in  the  case  of  those  who  in  railways 
or  upon  vessels  may  be  responsible  for  the  interpretation  of  signals. 
The  numerous  statistics  that  have  been  gathered  show  that  the 
defect  is  fairly  prevalent,  especially  among  men.  It  is  said  that 
on  the  average  from  2  to  4  per  cent,  are  color  blind  among  males, 
while  among  women  the  proportion  is  much  smaller, — 0.01  to  1  per 
cent.  Among  the  poorly  educated  classes  the  defect  is  said  to  be 
more  common  than  among  educated  persons.  Color  blindness 
may  exist  in  different  degrees  of  completeness,  from  a  total  loss  to 
a  simple  imperfection  or  feebleness  of  the  color  sense,  and  it  is 
usually  congenital.  Among  those  persons  who  possess  a  tri- 
chromatic color  sense  differences  may  be  observed  in  regard 
to  the  proportions  of  different  colors  which  must  be  combined 
to  make  a  match  with  a  given  standard.  This  condition  has 
been  shown  to  exist  particularly  for  the  combinations  of  red  and 
green  required  to  match  a  homogeneous  yellow.  Individuals 
who  differ  sensibly  from  the  normal  in  the  amounts  of  red  and 
green  selected  to  make  such  a  match  have  been  described  as 
having  an  "anomalous  trichromatic  vision. "f  Those  who  are 
completely  color  blind  as  regards  some  or  all  of  the  fundamental 

*  Holmgren,  "  Color  Blindness  in  its  Relations  to  Accidents  by  Rail  and 
Sea,"  "Smithsonian  Institution  Reports,"  Washington,  1878.  See  also  Jef- 
fries, "  Color  Blindness,  its  Danger  and  its  Detection,"  Boston. 

t  Consult  von  Kries  in  Nagel's  Handbuch  der  Physiologic,  vol.  3,  p.  124, 


PROPERTIES    OF    THE    RETINA.  355 

colors  fall  into  two  groups:  the  dichromatic,  whose  color  vision 
may  be  represented  by  two  fundamental  colors  and  their  com- 
binations with  white  or  black,  and  the  achromatic,  or  totally 
color  blind,  who  see  only  the  white-gray-black  series. 

Dichromatic  Vision. — The  color-blind  who  belong  to  this  class 
fall  into  two  or  three  groups,  which  have  been  designated,  under 
the  influence  of  the  Young-Helmholtz  theory  of  color  vision,  the 
red-blind,  the  green-blind,  and  the  violet-blind.  As  the  terms 
red-blind  and  green-blind  imply  a  more  specific  condition  of 
vision  than  is  found  to  be  the  case  on  careful  examination,  von 
Kries  has  suggested  as  a  substitute  the  names  protanopia  and 
deuteranopia,  as  indicating  a  defect  in  a  first  or  second  constit- 
uent necessary  for  color  vision.  According  to  the  same  nomen- 
clature, so-called  violet-blindness  would  be  designated  as  tritan- 
opia.  From  this  standpoint  genuine  color  blindness  may  be 
regarded  as  a  reduction  form  of  normal  trichromatic  vision  of 
such  a  character  that  all  the  color  sensations  may  be  conceived  as 
depending  upon  the  existence  of  only  two  fundamental  color 
processes.  The  most  common  by  far  of  these  groups  is  that  of  so- 
called  red-blindness  (protanopia);  it  constitutes  the  usual  form  of 
color  blindness.  As  a  matter  of  fact,  persons  so  affected  are  in  real- 
ity red-green  blind.  In  what  may  be  called  the  most  typical  cases 
they  distinguish  in  the  spectrum  only  yellows  and  blues.  The 
red,  orange,  yellow,  and  green  appear  as  yellow  of  different  shades, 
the  green-blue  as  gray,  and  the  blue- violet  and  purple  as  blue. 
The  red  end  of  the  spectrum  is  distinctly  shortened,  especially 
if  the  illumination  is  poor,  and  the  maximum  luminosity,  instead 
of  being  in  the  yellow,  as  in  normal  eyes,  is  in  the  green.  When 
the  spectrum  is  examined  by  such  persons  a  neutral  gray  band  is 
seen  at  the  junction  of  the  blue  and  green.  In  some  cases,  how- 
ever, this  neutral  band  is  not  seen,  the  yellow  passing  with  but 
little  change  into  the  blue.  As  a  matter  of  fact,  in  red-blindness 
the  most  characteristic  defect  is  a  failure  to  see  or  to  appreciate 
the  green.  This  color  is  confused  with  the  grays  and  with  dull 
shades  of  red.  When  such  persons  are  examined  for  their  negative 
after-images  for  different  colors,  it  will  be  noted  that  they  de- 
scribe some  of  their  after-images  as  red,  the  after-image  of  indigo- 
blue,  for  example,  but  that  they  describe  none  as  green.  The 
after-image  of  purple,  for  instance,  which  to  the  normal  eye  is 
bright  green,  is  described  by  them  as  gray  blue  or  pale  blue. 
From  the  descriptions  given  it  is  probable  that  the  color  vision 
of  the  so-called  red-blind  is  not  by  any  means  the  same  in  all  cases, 
but  exhibits  many  individual  differences.  The  green-blind  are 
also,  according  to  recent  descriptions,  red-green  blind;  they  also 


356  THE    SPECIAL    SENSES. 

confuse  reds  and  greens  and  in  the  spectrum  are  conscious  of  only 
two  color  qualities,  namely,  yellow  and  blue.  They  differ  from 
the  red-blind  in  that  the  red  end  of  the  spectrum  is  not  shortened, 
and  the  maximum  luminosity,  as  with  the  normal  eye,  is  placed 
in  the  yellow.  In  the  matching  and  combination  of  colors  they 
show  distinct  differences  from  the  red-blind,  so  that  though  re- 
sembling the  latter  in  general  features,  they  differ  obviously  in 
some  details.  As  compared  with  the  protanopes,  it  may  be  said 
that  their  retinas  are  more  sensitive  to  the  long  waves  in  the 
spectrum.  Violet  blindness  (tritanopia)  seems  to  be  so  rare 
as  a  congenital  and  permanent  condition  that  no  very  exact  study 
of  it  has  been  made.  In  cases  of  acquired  tritanopia  resulting 
from  pathological  changes  it  is  reported  that  the  violet  end  of 
the  spectrum  is  colorless  (neutral)  and  that  a  neutral  band  appears 
also  in  the  yellow-green  region  of  the  spectrum.*  By  the  ingestion 
of  santonin  it  is  said  that  a  condition  of  this  kind  may  be  produced 
temporarily.  The  violet  end  of  the  spectrum  is  shortened  and 
white  objects  take  on  a  yellowish  hue.  The  conditions  produced 
by  santonin  are  evidently  more  complex  than  can  be  explained 
by  simply  assuming  that  the  violet  color  sense  is  lost.  Recent 
observers  f  state  that  the  drug  produces  a  condition  of  yellow 
vision,  outside  the  fovea,  in  the  daylight,  and  a  condition  of 
violet  vision  with  yellow-blindness,  but  no  red-  or  green-blindness, 
in  dim  lights. 

Tests  far  Color  Blindness. — Although  the  vision  of  the  red  and 
the  green  blind  is  deficient  as  regards  green  and  red  colors,  it  will 
be  found  in  many  cases  that  they  recognize  these  colors  and  name 
them  correctly,  having  adopted  the  usual  nomenclature  and  adapted 
it  to  their  own  standards.  In  order  to  detect  the  deficiency  they 
must  be  examined  by  some  test  which  will  compel  them  to  match 
certain  colors.  Under  these  circumstances  it  will  be  found  that 
along  with  correct  matches  they  will  make  others  which  to  the  nor- 
mal eye  are  entirely  erroneous.  A  great  number  of  methods  have 
been  proposed  and  used  to  detect  color  blindness.  The  simplest 
perhaps  is  that  of  Holmgren.!  A  number  of  skeins  of  wool  are  used 
and  three  test  colors  are  chosen, — namely,  (I)  a  pale  pure  green 
skein,  which  must  not  incline  toward  yellow  green;  (II)  a  medium 
purple  (magenta)  skein;  and  (III)  a  vivid  red  skein.  The  person 
under  investigation  is  given  skein  I  and  is  asked  to  select  from  the 
pile  of  assorted  colored  skeins  those  that  have  a  similar  color  value. 
He  is  not  to  make  an  exact  match,  but  to  select  those  that  appear 

*  Collins  and  Nagel,  "Zeitschrift  f.  Psychol.  u.  Physiol.  d.  Sinnesorgane," 
1906,  xli.,  74. 

f  Sive"n  and  Wendt,  "  Skandinavisches  Archiv  f.  Physiologic,"  14,  196, 
1903,  and  1905,  17,  308. 

%  For  details  see  the  works  of  Holmgren  and  of  Jeffries,  already  quoted. 


PROPERTIES    OF   THE   RETINA.  357 

DO  have  the  same  color.  Those  who  are  red  or  green  blind  will  see 
the  test  skein  as  a  gray  with  some  yellow  or  blue  shade  and  will 
select,  therefore,  not  only  the  green  skeins,  but  the  grays  or  grayish 
yellow  and  blue  skeins.  To  ascertain  whether  the  individual  is  red 
or  green  blind  tests  II  and  III  may  then  be  employed. 

With  test  II,  medium  purple,  the  red  blind  will  select,  in  addition 
to  other  purples,  only  blues  or  violets ;  the  green  blind  will  select  as 
"confusion  colors"  only  greens  and  grays. 

With  test  III,  red,  the  red  blind  will  select  as  confusion  colors 
greens,  grays,  or  browns  less  luminous  than  the  test  color,  while  the 
green  blind  will  select  greens,  grays,  or  browns  of  a  greater  brightness 
than  the  test. 

Achromatic  Vision. — A  number  of  cases  of  total  color  blind- 
ness have  been  carefully  examined.*  It  would  seem  that  in 
such  individuals  there  is  an  entire  loss  of  color  sense, — they  possess 
only  achromatic  vision.  The  external  world  appears  to  them  only 
in  shades  of  gray.  In  the  majority  of  these  cases  (f)  there 
is  a  region  of  blindness  in  the  fovea  (central  scotoma),  and  an 
unusual  sensitiveness  to  light  and  nystagmus  (rolling  movement  of 
the  eyeballs)  are  also  characteristic.  Since  the  peripheral  field  of 
vision  is  nearly  normal  as  regards  sensitiveness  to  light,  while  the 
central  field  is  frequently  blind  or  amblyopic,  it  has  been  assumed 
that  this  condition  is  one  of  loss  of  function  in  the  cones. 

Distribution  of  the  Color  Sense  in  the  Retina. — What  has 
been  said  above  in  regard  to  color  blindness  refers  especially  to  the 
central  field  of  vision.  When  we  examine  the  peripheral  field  in 
the  normal  eye  it  is  found  that  on  the  extreme  periphery  the  retina 
is  totally  color  blind,  perceiving  only  light  and  darkness, — that  is, 
the  shades  of  gray.  As  we  pass  in  toward  the  center  the  color 
sense  develops  gradually,  the  blue  colors  being  perceived  first  and 
the  greens  last, — that  is,  nearest  to  the  center, — so  that  in  a  cer- 
tain zone  the  normal  eye  is  red-green  blind.  The  distribution  of 
the  color  sense  may  be  studied  conveniently  by  means  of  the  pe- 
rimeter (see  p.  341).  It  will  be  found  to  vary  with  each  individual, 
so  much  so  that  it  is  possible  that  a  test  of  this  character  might  be 
used  for  the  identification  of  individuals.  Exceptionally  it  is  found 
that  the  entire  retina  possesses  a  nearly  normal  color  sense.  Usu- 
ally for  the  colors  red,  green,  and  blue,  the  blue  has  the  most  exten- 
sive field  and  the  green  the  least,  as  is  indicated  in  the  perimeter 
chart  given  in  Fig.  150.  If  the  green  chosen  is  blue  green  (490  w) — 
that  is,  the  complementary  of  the  red — it  is  stated  that  their  fields 
are  co-extensive,  f  From  this  standpoint  the  retina  presents  three 

*  Grunert,  "Archiv  fur  Ophthalmologie,"  56,  132,  1903. 
t  Baird,  "The  Color  Sensitivity  of  the  Peripheral  Retina,"  Carnegie  Pub- 
lication, No.  29,  1905. 


358 


THE   SPECIAL   SENSES. 


concentric  zones:  an  extreme  peripheral  zone  devoid  of  color  vis- 
ion, an  intermediate  zone  in  which  yellow  and  blue  are  perceived, 
and  a  central  zone  sensitive  to  red  and  green.*  The  outlines  of 


osi 


Fig.  150. — Perimeter  chart  indicating  the  average  fields  of  vision  for  blue,  red,  and 
green  compared  with  white  (gray).  Right  eye:  The  outlines  of  the  color  fields  are  repre- 
sented as  smooth  since  the  chart  is  an  average  from  many  determinations.  As  a  matter  of 
fact,  in  each  individual  the  outline  is  highly  irregular.  Normally  green  (bright  green)  is  the 
smallest  field,  green  objects  outside  the  limit  appearing  yellow  and  farther  out  colorless 
(gray). 

the  different  fields  usually  show  many  irregularities,  and  in  some 
cases  it  will  be  found  that  bright  green  is  perceived  over  a  larger  area 
than  the  red.  The  fields  are  not  identical  in  the  two  eyes,  and  in 
each  eye  it  is,  as  a  rule,  more  extensive  upon  the  nasal  than 
upon  the  temporal  side  of  the  retina.  In  the  red-green  blind  the 
peripheral  fields  of  color  vision,  judged  by  the  individual's  own 
standards,  may  be  markedly  constricted  as  compared  with  the  nor- 
mal retina  (see  Fig.  151). 

Functions  of  the  Rods  and  Cones. — Many  facts  unite  in  mak- 
ing it  probable  that  the  rods  and  cones  are  different  in  function. 
They  differ  in  structure  and  especially  in  their  connections.  As  is 
shown  in  the  diagram  given  in  Fig.  152,  the  cones  terminate  in  the 
external  nuclear  layer  in  arborizations  which  connect  with  the  bi- 
polar ganglion  cells,  and  in  the  fovea  at  least  this  connection  is  such 

*  It  is  interesting  to  find  (Haycraft)  that  around  the  blind  spot  there  is  a 
small  zone  which,  like  the  periphery  of  the  retina,  is  completely  color-blind, 
that  is,  perceives  only  gray,  and  external  to  this  the  color  sense  is  developed 
in  zones  whose  order  is  similar  to  that  on  the  periphery  of  the  retina. 


PROPERTIES    OF   THE    RETINA.  359 

that  each  cone  connects  with  a  single  nerve  cell  and  eventually  per- 
haps with  a  single  optic  nerve  fiber.  The  rods,  on  the  contrary, 
end  in  a  single  knob-like  swelling,  and  a  number  of  them  make  con- 
nections with  the  same  nerve  cell.  Histologically,  therefore,  the 


Fig.  151. — Perimeter  chart  showing  the  highly  restricted  color  fields  in  the  left  eye 
of  a  typical  case  of  so-called  red-green  color  blindness.  The  ability  to  distinguish  red  and 
green,  by  whatever  characteristics  of  intensity  or  color  they  possessed  extended  for  a  very 
short  distance  outside  the  fovea.  It  is  interesting  that  the  ability  to  distinguish  blue  was 
in  this  case  limited  as  compared  with  a  normal  eye. 


conduction  paths  for  the  cones  seem  to  be  more  direct  than  in 
the  case  of  the  rods.  These  latter  elements,  moreover,  possess  the 
visual  purple,  which  is  lacking  in  the  cones.  Lastly,  in  the  eye  of 
the  totally  color  blind,  in  the  dark-adapted  eye  in  dim  lights,  in  the 
color-blind  peripheral  area  of  the  normal  eye,  and  in  the  eyes  of 
most  distinctly  night-seeing  animals,  such  as  the  mole  and  the  owl, 
vision  seems  to  be  effected  solely  by  the  rods.  These  facts  find 
their  simplest  explanation  perhaps  in  the  view  advocated  by  Pari- 
naud,  Franklin,  von  Kries,*  and  others,  according  to  which  the 
perception  of  color  is  a  function  of  the  cones  alone,  while  the  rods 
are  sensitive  only  to  light  and  darkness,  and  by  virtue  of  their  power 
of  adaptation  in  the  dark  through  the  regeneration  of  their  visual 
purple,  they  form  also  the  special  apparatus  for  vision  in  dim 

*  Von  Kries,  "Zeitschrift  f.  Psychologie  u.  Physiol.  d.  Sinnesorgane,"  9, 
81,  1895. 


360 


THE    SPECIAL   SENSES. 


lights  (night  vision).  Color  blindness,  therefore,  whether  total  or 
partial,  may  be  regarded  as  an  affection  or  lack  of  normal  develop- 
ment of  the  cones.  On  the  other  hand,  those  interesting  cases  in 


Fig.  152. — Schema  of  the  structure  of  the  human  retina  (Greeff):  I,  Pigment  layer; 
II,  rod  and  cone  layer;  ///,  outer  nuclear  layer;  IV,  external  plexiform  layer;  V,  layer 
of  horizontal  cells;  VI,  layer  of  bipolar  cells  (inner  nuclear) ;  VII,  layer  of  amacrinal  cells 
(without  axons) ;  VIII,  inner  plexiform  layer ;  IX,  ganglion  cell  layer ;  X ,  nerve  fiber 
layer;  6,  fiber  of  Muller. 

which  the  vision,  while  good  in  daylight,  is  faulty  or  lacking  in  dim 
lights  (night  blindness,  hemeralopia)  may  be  referred  to  a  defective 
functional  activity  of  the  rods,  probably  from  lack  of  formation  of 
visual  purple. 

Theories  of  Color  Vision. — A  number  of  theories  have  been 
proposed  to  explain  the  facts  of  color  vision.  None  of  them  has 
been  entirely  successful  in  the  sense  that  the  explanations  it  affords 


PROPERTIES    OF   THE    RETINA.  361 

have  been  submitted  to  satisfactory  experimental  verification.  The 
immediate  stimuli  that  give  rise  to  the  visual  impulses  are  assumed 
to  be  of  a  chemical  nature,  and  it  seems  probable  that  in  this 
case  as  in  that  of  many  other  problems  of  physiology,  we  must 
await  the  development  of  a  more  complete  knowledge  of  the 
chemical  processes  involved.  The  theories  proposed  at  present, 
while  all  tested  by  experimental  inquiries,  are  in  a  large  measure 
hypotheses  constructed  to  fit  more  or  less  completely  the  facts  that 
are  known.  Three  of  these  theories  may  be  described  briefly  as 
examples  of  the  modes  of  reasoning  employed: 

I.  The  Young-Hdmholtz  Theory. — This  theory,  proposed  essen- 
tially by  Thomas  Young  (1807)  and  afterward  modified  and  ex- 
panded by  Helmholtz,*  rests  upon  the  assumption  that  there  are 
three  fundamental  color  sensations, — red,  green,  and  violet — and 
corresponding  with  these  there  are  three  photochemical  substances 
in  the  retina.  By  the  decomposition  of  each  of  these  substances  cor- 
responding nerve  fibers  are  stimulated  and  impulses  are  conducted 
to  a  special  system  of  nerve  cells  in  the  visual  center  of  the  cerebrum. 
The  theory,  therefore,  assumes  special  nerve  fibers  and  nerve  centers 
corresponding  respectively  to  the  red,  green,  and  violet  photo- 
chemical substances,  and  the  peculiar  quality  of  the  resulting  sensa- 
tions are  referred,  in  the  original  theory,  to  the  different  reactions 
in  consciousness  in  the  three  corresponding  centers  in  the  brain. 
When  these  three  substances  are  equally  excited  a  sensation  of 
white  results,  of  greater  or  less  intensity  according  to  the  extent  of 
the  excitation.  White,  therefore,  on  this  theory,  is  a  compound 
sensation  produced  by  the  combination  or  fusion  in  consciousness 
of  the  three  equal  fundamental  color  sensations.  The  sensation  of 
black,  on  the  other  hand,  results  from  the  absence  of  stimulation, 
from  the  condition  of  rest  in  the  retina  and  in  the  corresponding 
nerve  fibers  and  nerve  centers.  All  other  color  sensations — yellow, 
for  instance — are  compound  sensations  produced  by  the  combined 
stimulation  of  the  three  photochemical  substances  in  different  propor- 
tions. It  is  assumed,  furthermore,  that  each  of  the  photochemical 
substances  is  acted  upon  more  or  less  by  all  of  the  visible  rays  of  the 
spectrum,  but  that  the  rays  of  long  wave  lengths  at  the  red  end 
of  the  spectrum  affect  chiefly  the  red  substance,  those  corresponding 
to  the  green  of  the  spectrum  chiefly  the  green  substance,  and  the 
rays  of  shortest  wave  length  chiefly  the  violet  substance.  These  rela- 
tionships are  expressed  in  the  diagram  given  in  Fig.  153)  The  figure 
also  indicates  that  it  is  impossible  to  stimulate  any  one  of  these  sub- 
stances entirely  alone, — that  is,  we  cannot  obtain  a  perfectly  satu- 
rated color  sensation.  Even  the  extreme  red  or  the  extreme  violet 

*  Helmholtz,  "Handbuch  der  physiologischen  Optik,"  second  edition. 
1896,  I,  344. 


362 


THE   SPECIAL   SENSES. 


rays  act  more  or  less  on  all  of  the  substances,  and  the  resulting  red 
or  violet  sensation,  is,  therefore,  mixed  to  some  extent  with  white, — 
that  is,  is  not  entirely  saturated.  The  theory,  as  stated  by  Helm- 
holtz,  held  strictly  to  the  doctrine  of  specific  nerve  energy,  in  assuming 
that  each  photochemical  substance  serves  simply  as  a  means  for  the 
excitation  of  a  nerve  fiber,  and  that  the  quality  of  the  sensation 
aroused  depends  on  the  ending  of  this  fiber  in  the  brain.  The  phe- 
nomenon of  negative  after-images  finds  a  simple  explanation  in  terms 
of  this  theory.  If  we  look  fixedly  at  a  green  object,  for  example, 
the  corresponding  photochemical  substance  is  chiefly  acted  upon,  and 
if  subsequently  the  same  part  of  the  retina  is  exposed  to  white  light, 
the  red  and  violet  substances,  having  been  previously  less  acted 
upon,  now  respond  in  greater  proportions  to  the  white  light,  and 


R 


B 


Fig.  153. — Schema  to  illustrate  the  Young-Helmholtz  theory  of  color  vision. — (Helm- 
holtz.)  The  spectral  colors  are  arranged  in  their  natural  order, — red  to  violet.  The  curyeg 
represent  the  intensity  of  stimulation  of  the  three  color  substances:  1,  The  red  perceiving 
substance;  2,  the  green  perceiving;  3,  the  violet  perceiving.  Verticals  drawn  at  amr 
point  of  the  spectrum  indicate  the  relative  amount  of  stimulation  of  the  three  substances 
for  that  wave  length  of  the  spectrum. 

the  after-image  takes  a  red- violet — that  is,  purple— color.  Many 
objections  have  been  raised  to  the  Young-Helmholtz  theory.  It 
has  been  urged,  for  instance,  that  we  are  not  conscious  that  white 
or  yellow  sensations  are  blends  or  compounded  color  sensations; 
we  perceive  in  them  none  of  the  supposed  component  elements  as 
we  do  in  such  undoubted  mixtures  as  the  blue-greens  or  the  purples. 
The  theory  explains  poorly  or  not  at  all  the  fact  that  on  the  periphery 
of  the  retina  we  are  color  blind  and  yet  can  perceive  white  or  gray, 
and  it  breaks  down  also  in  the  face  of  the  facts  of  partial  and  com- 
plete color  blindness.  The  explanation  given  for  black  is  also 
unsatisfactory  in  that  it  assumes  an  active  state  of  consciousness 
associated  with  a  condition  of  rest  in  the  visual  mechanism. 

II.  Hering's  Theory  of  Color  Vision. — This  theory  also  assumes 
the  existence  in  the  retina  of  three  photochemical  substances,  but 
of  such  a  nature  as  to  give  us  six  different  qualities  of  sensation. 
There  is  a  white-black  substance  which  when  acted  upon  by  the 


PROPERTIES    OF   THE    RETINA. 


363 


visible  rays  of  light  undergoes  disassimilation  and  sets  up  nerve 
impulses  that  arouse  in  the  brain  the  sensation  of  white.  On  the 
other  hand,  when  not  acted  upon  by  light  this  same  substance  under- 
goes assimilatory  processes  that  in  turn  set  up  nerve  impulses  which 
in  the  brain  give  us  a  sensation  of  black.  There  are  in  the  retina  also 
a  red-green  and  a  yellow-blue  substance.  The  former  when  acted 
upon  by  the  longer  rays  undergoes  disassimilation  and  gives  a 
sensation  of  red,  while  the  shorter  waves  cause  assimilation  and 
produce  a  sensation  of  green.  A  similar  assumption  is  made  for 
the  yellow-blue  substance.  The  essence  of  the  theory  may  be  stated, 
therefore,  in  tabular  form,  as  follows  *: 


PHOTOCHEMICAL  SUBSTANCE. 


RETINAL  PROCESS. 


^low-blue 


White-black. 


f  Disassimilation 
1  Assimilation 


SENSATION. 

=  red 

=  green 

=  yellow 

=  blue 

=  white 

=  black 


It  will  be  observed  that  the  theory  gives  an  independent  ob- 
jective cause  for  the  sensations  of  white,  black,  and  yellow,  and  in 


Fig.  154. — Schema  to  illustrate  the  Hering  theory  of  color  vision. — (Foster.)  The 
curves  indicate  the  relative  intensities  of  stimulation  of  the  three  color  substances  by  dif- 
ferent parts  of  the  spectrum.  Ordinates  above  the  axis,  X-X,  indicate  catabolic  changes 
(disassimilation),  those  below  anabolic  changes  (assimilation).  Curve  a  represents  the 
conditions  for  the  black-white  substance.  It  is  stimulated  by  all  the  rays  of  the  visible 
spectrum  with  maximum  intensity  in  the  yellow.  Curve  c  represents  the  red-green  sub- 
stance, the  longer  wave  lengths  causing  disassimilation  (red),  the  shorter  ones  assimilation 
(green).  Curve  6  gives  the  conditions  for  the  yellow-blue  substance. 

this  respect  satisfies  the  objections  made  on  this  score  to  the  Young- 
Helmholtz  theory.  It  fits  better,  also,  the  facts  of  partial  and  total 
color  blindness.  In  the  latter  condition  one  may  assume,  in  terms  of 

*  For  discussion  of  color  theories  see  Calkins,  "Archiv  f.  Physiologie," 
1902,  suppl.  volume,  p.  244;  also  Greenwood  in  Hill's  "Further  Advances 
in  Physiology  "  p.  378,  1909. 


364 


THE   SPECIAL   SENSES. 


this  theory,  that  only  the  white-black  substance  is  present,  while 
red  and  green  blindness — both  of  them,  it  will  be  recalled,  really 
forms  of  red-green  blindness — are  explained  on  the  view  that  in  such 
persons  the  red-green  substance  is  deficient  or  lacking.  On  this 
theory,  complementary  colors — red  and  blue-green,  yellow  and 
blue — are,  in  reality,  antagonistic  colors.  When  thrown  on  the 

retina  simultaneously  their 
effects  neutralize  each  other, 
and  there  remains  over  only 
the  disassimilatory  effect  on 
the  white  substance  which  is 
exerted  by  all  the  visible 
rays.  The  effect  of  the  vari- 
ous visible  rays  of  the  spec- 
trum on  the  three  photo- 
chemical substances  is  illus- 
trated by  the  chart  given  in 
Fig.  154.  Ordinates  above 
the  abscissa  representing  dis- 
assimilatory effects;  those 
below,  assimilatory. 

///.  The  Franklin  Theory 
of  Color  Vision  (Molecular 
Dissociation  Theory) . — This 
theory,  proposed  by  Mrs.  C. 
L.  Franklin,*  takes  into  ac- 
count the  fact  of  a  gradual 
evolution  of  the  color  sense 
of  the  retina  from  a  primitive 
condition  of  colorless  vision 
such  as  still  exists  in  the 
periphery  of  the  retina  and 
in  the  eyes  of  the  totally 
color  blind.  It  assumes  that 
the  colorless  sensations — 
white,  gray,  black — are  occa- 
sioned by  the  reactions  of  a 
photochemical  material 


Fig.  155.— Schema  to  illustrate  the  Frank- 
lin theory  of  color  vision  (Franklin) :  W,  The 
molecule  of  the  primitive  visual  (gray-perceiv- 
ing) substance;  Y  and  B,  the  first  step  in  the 
differentiation  into  a  yellow-  and  a  blue-per- 
ceiving substance,  whose  combined  dissociation 
gives  the  same  effect  as  that  of  the  original  sub- 
stance, W;  O  and  R,  the  second  step  in  the 
differentiation  of  the  yellow-perceiving  sub- 
stance, the  combined  dissociation  of  the  two 


giving  the  same  effect  as  that  of  the  yellow-per- 
ceiving substance  alone.  The  complete  devel- 
opment of  color  vision  as  it  exists  hi  the  central 
part  of  the  retina  consists  in  the  existence  of 
three  substances,  which,  taken  separately,  give 
red,  green,  and  blue  color  sensations. 


which    for  convenience  may 
be   designated  as  the   gray 

substance.  This  substance  in  the  normal  eye  exists  in  both  rods 
and  cones;  in  the  latter,  however,  in  a  differentiated  condition 
capable  of  giving  color  sensations.  When  the  molecules  of  this 
substance  are  completely  dissociated  by  the  action  of  light,  gray 

*  Franklin,  "Zeitschrift  f.  Psychologie  und  Phys.  d.  Sinnesorgane , "  1892, 
iv;  also  "Mind,"  2,  473,  1893,  and  "Psychological  Review,"  1894,  1896,  1899. 


PROPERTIES    OF   THE    RETINA.  365 

sensations  result,  and  as  this  is  the  only  reaction  possible  in  the 
rods  these  elements  can  furnish  us  only  sensations  of  this  quality. 
The  molecules  of  gray  substance  in  the  cones,  on  the  other 
hand,  have  undergone  a  development  such  that  certain  portions 
only  of  the  molecule  may  become  dissociated  by  the  action  of  light 
of  certain  periods  of  vibration.  This  development  may  be  sup- 
posed to  have  taken  place  in  two  stages:  first,  the  formation  of 
two  groupings  within  the  molecule,  one  of  which  is  dissociated  by 
the  longer  waves  and  gives  a  sensation  of  yellow,  and  one  of  which 
is  dissociated  by  the  shorter  waves  and  gives  the  sensation  of 
blue.  This  stage  remains  still  on  portions  of  the  periphery  of  the 
retina,  and  is  the  condition  present  in  the  fovea  also  in  the  eyes 
of  the  red-green  blind.  The  second  stage  consists  in  the  division 
of  the  yellow  component  into  two  additional  groupings  in  one 
of  which  the  internal  movements  are  of  such  a  period  as  to  be 
affected  by  the  longest  visible  waves,  the  red  of  the  spectrum, 
while  the  other  is  dissociated  by  rays  corresponding  to  the  green 
of  the  spectrum  and  gives  rise  to  the  sensation  of  green.  If 
the  red  and  green  groupings  are  dissociated  together  the  resulting 
effect  is  the  same  as  follows  from  the  dissociation  of  the  entire  yellow 
component,  while  the  complete  dissociation  of  the  red,  green,  and 
blue  groupings  gives  the  stimulus  obtained  originally  from  the  disso- 
ciation of  the  whole  molecule,  and  causes  gray  sensations.  The  idea 
of  this  subdivision  or  differentiation  in  structure  of  the  original  gray 
substance  is  indicated  diagrammatically  in  Fig.  155.  The  theory 
accounts  admirably  for  many  phenomena  in  vision,  and  is  perhaps 
especially  adapted  to  explain  the  facts  of  color  blindness  and  the 
variations  in  quality  of  our  visual  sensations  in  the  peripheral  areas 
of  the  retina.  An  extension  and  modification  of  this  theory 
has  been  published  by  Schenck.*  He  assumes  that  each  of  the 
three-color  perceiving  substances  is  composed  of  two  parts. 
One  part  which  acts  as  a  receiver  for  the  stimulus,  a  sort  of  an 
optical  resonator,  in  fact,  and  a  second  part  which  is  set  into 
activity  by  the  receiver  and  gives  rise  to  the  corresponding 
color  sensation.  The  theory  is  very  elastic  in  its  adaptability 
to  the  various  kinds  of  color  blindness. 

The  two  latter  theories  seem  to  imply  that  a  number  of  different  kinds 
of  impulses  may  be  transmitted  along  the  optic  fibers.  Hering's  theory  re- 
quires apparently  the  possibility  of  six  qualitatively  different  impulses, — 
namely,  white,  black,  red,  green,  yellow,  and  blue, — while  the  Franklin  theory 
assumes  impulses  corresponding  to  white  (gray),  red,  green,  yellow,  and  blue. 
Black  is  not  specifically  accounted  for  except  as  a  part  of  the  gray  series.  At 
present  in  physiology  there  is  no  proof  that  nerve  impulses  can  differ  quali- 
tatively from  each  other,  although  it  may  be  urged,  perhaps  with  equal  force, 
that  there  is  no  proof  that  they  can  not  so  differ.  The  doctrine  of  specific 
nerve  energy  assumes  that  nerve  impulses  are,  as  regards  quality,  always 

*  Schenck,  "Archiv  f.  d.  gesammte  Physiologie, "  118,  129,  1907. 


366  THE    SPECIAL    SENSES. 

the  same,  and  differ  from  one  another  only  in  intensity,  the  qualitative  differ- 
ences that  exist  among  sensations  being  referred  to  a  difference  in  reaction 
in  the  end-organ  in  the  brain. 

Entoptic  Phenomena. — Under  the  term  entoptic  phenomena 
is  included  a  number  of  visual  sensations  due  to  the  shadows  of 
various  objects  within  the  eyeball  itself.  Ordinarily  these  shadows 
are  imperceptible,  owing  to  the  diffuse  illumination  of  the  interior 
of  the  eye  through  the  relatively  wide  opening  of  the  pupil.  By 
means  of  various  devices  the  illumination  of  the  eye  may  be  so 
controlled  as  to  make  these  shadows  more  distinct  and  thus  bring 
the  retinal  images  into  consciousness.  Some  of  these  entopic  ap- 
pearances are  described  briefly,  but  for  a  detailed  description  the 
reader  is  referred  to  the  classical  work  of  Helmholtz.* 

The  Blood-corpuscles. — The  entoptic  images  that  are  most  easily 
recognized  perhaps  are  those  of  the  moving  corpuscles  in  the  capil- 
laries of  the  retina.  If  one  looks  off  into  the  blue  sky  he  will  have 
no  difficulty  in  recognizing  a  number  of  minute  clear  and  dark  specks 
that  move  in  front  of  the  eye  in  definite  paths.  The  character  of 
the  movement  leaves  no  doubt  that  these  sensations  are  due  to  the 
shadows  of  the  blood-corpuscles.  In  fact,  the  shadows  often  show 
a  rhythmic  acceleration  in  velocity  synchronous  with  the  heart- 
beats, a  pulse  movement.  By  projecting  the  moving  images  upon 
a  screen  at  a  known  distance  from  the  eye  the  velocity  of  the  capil- 
lary circulation  has  been  estimated  in  man. 

The  Retinal  Blood-vessels. — The  blood-vessels  of  the  retina  lie 
in  front  of  the  rods  and  cones  and  must  necessarily  throw  their 
shadows  upon  these  sensitive  end-organs.  The  shadows  may  be 
made  more  distinct  and  a  visual  picture  of  the  vessels  obtained  by 
a  number  of  methods.  For  instance,  if  a  card  with  a  pin  hole 
through  it  is  moved  slowly  in  front  of  the  eye  the  images  of  the 
blood-vessels  stand  out  in  the  field  of  vision  with  more  or  less 
distinctness.  The  card  should  be  given  a  circular  movement.  If  it 
is  kept  in  one  position  the  images  quickly  disappear,  since  the 
retina  apparently  fatigues  very  quickly  for  such  faint  impressions. 
A  more  impressive  picture  may  be  obtained  by  the  method  of 
Purkinje.  In  a  dark  room  one  holds  a  candle  toward  the  side  of  the 
head  in  such  a  position  as  to  give  the  sensation  of  a  glare  in  the 
corresponding  eye.  If  the  eye  is  directed  toward  the  opposite 
side  of  the  room  and  the  candle  is  kept  in  continual  circular 
movement  the  blood-vessels  appear  in  the  field  of  vision  magni- 
fied in  proportion  to  the  distance  of  projection;  the  picture  makes 
the  impression  of  a  thicket  of  interlacing  branches.  In  this  ex- 
periment the  light  from  the  candle  strikes  the  nasal  side  of  the 

*  Helmholtz,  "Handbuch  der  physiologischen  Optik,"  second  edition. 
I,  184. 


PROPERTIES    OF   THE    RETINA. 


367 


retina  at  an  oblique  angle  and  is  reflected  toward  the  other  side 
of  the  globe.  The  blood-vessels  are  in  this  way  illuminated  from 
an  unusual  direction  and  their  shadows  are  thrown  upon  a  por- 
tion of  the  retina  not  usually  affected  and  for  that  reason  perhaps 
more  sensitive  to  the  impression. 

Imperfections  in  the  Vitreous  Humor  and  the  Lens. — Small  frag- 
ments of  the  cells  from  which  the  vitreous  humor  was  constructed 
in  the  embryo  and  simi- 
lar relatively  opaque  ob- 
jects  in  the  lens  may 
throw  shadows  on  the 
retinal  bottom.  These 
shadows  take  different 
forms,  but  usually  are  de- 
scribed as  small  spheres 
or  beads,  single  or  in 
groups,  that  move  with 
the  eyes  and  are  desig- 
nated, therefore,  as  the 
muscae  volitantes  (flitting 
flies  or  floating  flies).  To 

bring  out  these  shadows  it  is  convenient  to  make  the  source  of  illu- 
mination small  and  to  bring  it  at  or  nearer  than  the  anterior  focal 
distance  of  the  eye  (15  to  16  mms.).  The  method  employed  for  this 
purpose  by  Helmholtz  is  illustrated  in  Fig.  156.  In  this  figure  b 
is  a  candle  flame,  and  a  a  lens  of  short  focus  which  makes  an  image 
of  the  flame  at  the  small  opening  shown  in  the  dark  screen,  c.  The 
eye  is  placed  just  behind  this  opening  and  is  illuminated  by  the  rays 
from  the  small,  bright  image  of  the  flame  at  that  spot.  The  shadows 
are  seen  projected  upon  the  illuminated  surface  of  the  glass  lens. 


Fig.  156. — Helmholtz's  method  of  showing  en- 
toptic  phenomena  due  to  imperfections  in  the  lens 
and  vitreous  (Helmholtz):  c,  a  screen  with  pinhole; 
a,  lens  with  short  focus. 


CHAPTER  XIX. 
BINOCULAR  VISION. 

Vision  with  two  eyes  differs  from  monocular  vision  chiefly  in 
the  varied  combinations  of  movements  of  the  two  eyeballs  and  the 
aid  thereby  afforded  in  the  determination  of  distance  and  size, 
in  the  enlarged  field  of  vision,  and,  above  all,  in  the  more  exact  per- 
ception of  solidity  or  perspective,  especially  for  near  objects. 

The  Movements  of  the  Eyeballs. — Each  eyeball  is  moved 
by  six  extrinsic  muscles  which  are  innervated  through  three 
cranial  nerves.  The  third  or  oculomotor  nerve  controls  the  internal 
rectus,  the  superior  rectus,  the  inferior  rectus,  and  the  inferior 
oblique;  the  fourth  cranial  nerve  (n.  patheticus)  innervates  the 
superior  oblique  alone;  and  the  sixth  cranial  (n.  abducens)  the 
external  rectus  alone.  By  means  of  these  muscles  the  eyeballs  may 
be  given  various  movements,  all  of  which  may  be  considered  as 
rotations  of  the  ball  around  various  axes.  The  common  point  of 
intersection  of  these  axes  is  designated  as  the  rotation  point  or 
center  of  rotation  of  the  eyeball;  it  lies  about  13.5  mms.  back  of  the 
cornea  in  the  emmetropic  eye.  The  various  axes  of  rotation  all 
pass  through  this  point,  and  we  may  classify  them  under  four 
heads:  (1)  The  horizontal  or  sagittal  axis,  which  is  the  line  passing 
through  the  rotation  point  and  the  object  looked  at, — the  fixation 
point.  This  axis  corresponds  practically  with  the  line  of  sight, — 
that  is,  the  line  drawn  from  the  object  looked  at  to  the  middle  of  the 
fovea,  and  it  may  therefore,  without  serious  error,  be  spoken  of  as 
the  visual  axis.  Rotations  around  this  axis  give  a  wheel  movement 
or  torsion  to  the  eyeballs.  (2)  The  transverse  axis,  the  line  passing 
through  the  rotation  points  of  the  two  eyes  and  perpendicular 
to  1.  Rotations  around  this  axis  move  the  eyeballs  straight  up 
or  down.  (3)  The  vertical  axis,  the  vertical  line  passing  through 
the  rotation  point  and  perpendicular  at  this  point  to  the  horizontal 
and  transverse  axes.  Rotations  around  this  axis  move  the  eyeball 
to  the  right  or  the  left.  (4)  The  oblique  axes,  under  which  are  in- 
cluded all  the  axes  of  rotation  passing  through  the  rotation  point  at 
oblique  angles  to  the  horizontal  axis.  These  axes  all  lie  in  the 
equatorial  plane  of  the  eye,  and  rotations  around  any  of  them  move 
the  eyeball  obliquely  upward  or  downward.  These  definitions  all 
have  reference  to  what  is  known  as  the  primary  position  of  the 

368 


BINOCULAR   VISION.  369 

eyeS;_that  is,  that  position  taken  by  the  eyes  when  we  look  straight 
before  us  toward  the  horizon,— a  position,  therefore,  in  which  the 
plane  of  the  horizontal  axes  is  parallel  to  the  ground;  all  other 
positions  of  the  eyes  are  spoken  of  as  secondary. 

With  regard  to  the  movements  of  the  eyes  about  Its  axes  of 
rotation  the  following  general  statements  are  made :  Starting  from 
the  primary  position,  rotations  of  the  eyes  about  the  vertical  axis— 
that  is,  movements  directly  to  right  or  left— may  be  made  by  the 
contraction  of  the  internal  or  the  external  rectus  as  the  case  may  be. 
Rotations  around  the  transverse  axis— that  is,  movements  directly 
up  or  down — require  in  each  case  the  co-operation  of  two  muscles. 
In  movements  upward  the  superior  rectus,  acting  alone,  would  in 


Fig.  157. — "  Diagram  showing  for  the  left  eye  the  paths  of  the  line  of  sight  caused  by  the 
action  of  the  different  eye-muscles  (Hering).  The  horizontal  line  indicates  movements  out  or 
in  to  various  degrees  as  caused  by  the  contraction  of  the  internal  or  external  rectus.  The 
curved  lines  show  the  amount  of  torsion  given  the  eyeball  by  the  superior  and  inferior 
rectus  and  the  superior  and  inferior  oblique  when  contracting  separately.  Tne  short 
heavier  line  at  the  end  of  the  paths  indicates  the  position  of  the  horizontal  meridian  at 
the  end  of  the  movement."  R.  e.,  the  external  rectus;  R,  i.,  the  internal  rectus;  R.  S., 
the  superior  rectus;  R.  inf.,  the  inferior  rectus;  O.  i.,  the  inferior  oblique;  O.  S.t  the  superior 
oblique. 

rotating  the  eyeball  upward  also  give  it  a  slight  torsion  so  as  to 
turn  the  upper  part  of  the  vertical  meridian  inward.  To  obtain  a 
movement  directly  upward  (rotation  around  the  transverse  axis) 
the  superior  rectus  and  inferior  oblique  must  act  together.  For 
a  similar  reason  rotation  directly  downward  requires  the  com- 
bined action  of  the  inferior  rectus  and  superior  oblique.  These 
facts  are  expressed  clearly  in  Hering' s  diagram,  reproduced  in 
Fig.  157,  which  indicates  the  paths  traversed  by  the  line  of  sight 
when  the  eyeball  is  moved  by  the  different  muscles  acting  sepa- 
rately. Rotation  of  the  eyeballs  around  oblique  axes  require 
the  co-operation  of  three  of  the  muscles  :  movements  upward 
and  outward — the  superior  rectus,  inferior  oblique,  and  external 
rectus;  movements  upward  and  inward — superior  rectus,  inferior 
24 


370  THE  SPECIAL  SENSES. 

oblique,  and  internal  rectus;  movements  downward  and  outward— 
inferior  rectus,  superior  oblique,  and  external  rectus;  movements 
downward  and  inward — inferior  rectus,  superior  oblique,  and 
internal  rectus.  Most  of  the  movements  of  the  eyes  are  of  the 
latter  kind, — namely,  rotations  around  an  oblique  axis, — and 
the  position  of  the  axis  for  each  definite  movement  of  this  character 
may  be  determined  by  Listing's  law,  which  may  be  stated  as 
follows  :  When  the  eye  passes  from  a  primary  to  a  secondary 
position  it  may  be  considered  as  having  rotated  around  an  axis 
perpendicular  to  the  lines  of  sight  in  the  two  positions.  It  will 
be  noted  readily  from  observations  upon  the  movements  of  one's 
own  eyes  that  they  ordinarily  make  only  such  movements  as  will 
keep  the  lines  of  sight  of  the  two  eyes  parallel  or  will  converge 
them  upon  a  common  point.  In  movements  of  convergence  the 
internal  recti  of  the  two  eyes  are  associated,  while  in  symmetrical 
lateral  movements  the  internal  rectus  of  one  eye  acts  with  the 
external  rectus  of  the  other.  Under  normal  conditions  it  is 
impossible  for  us  to  diverge  the  visual  axes, — that  is,  to  associate 
the  action  of  the  external  recti.  A  movement  of  this  kind  would 
produce  useless  double  vision  (diplopia),  and  it  is,  therefore,  a 
kind  of  movement  which  all  of  our  experience  has  trained  us 
to  avoid. 

The  Co-ordination  of  the  Eye  Muscles — Muscular  Insuf- 
ficiency— Strabismus. — In  order  that  the  eyeballs  may  move  with 
the  minute  accuracy  necessary  in  binocular  vision,  a  beautifully 
balanced  or  co-ordinated  action  of  the  opposing  muscles  is  neces- 
sary. The  object  of  these  movements  is  to  bring  the  point  looked 
at  in  the  fovea  of  each  eye  and  thus  prevent  double  vision,  diplopia 
(see  following  paragraphs).  This  object  is  attained  when  the  eye- 
balls are  so  moved  that  the  lines  of  sight  unite  upon  the  object  or 
point  looked  at.  In  viewing  an  object  or  in  reading  we  keep 
readjusting  the  eyes  continually  to  bring  point  after  point  at  the 
junction  of  the  lines  of  sight.  When  we  look  before  us  at  a 
distant  object  the  muscles  in  each  eye  should  be  so  adjusted 
that  without  any  contraction  the  antagonistic  muscles  will 
just  balance  each  other — that  is,  when  the  eye  muscles  are 
entirely  relaxed,  except  for  their  normal  tone,  the  visual  axes 
should  be  parallel.  If  this  balance  does  not  exist,  we  have  a 
condition  designated  as  heterophoria.  In  this  condition  a 
constant  contraction  of  one  or  more  muscles  is  required,  even 
in  far  vision,  to  prevent  diplopia.  When  the  eye  at  rest  shows 
a  tendency  to  drift  toward  the  temporal  side,  owing  to  the  fact 
that  the  pull  of  the  external  rectus  overbalances  that  of  the 
internal  rectus,  the  condition  is  known  as  exophoria.  If,  for  the 
opposite  reason,  there  is  a  tendency  to  drift  to  the  nasal  side,  the 


BINOCULAK    VISION.  371 

condition  is  described  as  esophoria.  A  tendency  to  drift  up  or 
down  is  called  hyperphoria,  and  this  is  further  specified  as  right 
or  left  hyperphoria  according  to  the  eye  whose  axis  deviates 
upward.  A  lack  of  resting  balance  of  this  kind  may  make  itself 
felt  also  in  near  work,  particularly  in  reading,  sewing,  etc.,  since 
it  will  require  a  constantly  greater  innervation  of  the  muscle 
whose  antagonist  overbalances  it.  Under  some  conditions  the 
resulting  muscular  strain  causes  much  uneasiness  or  distress. 
The  heterophorias  are  easily  detected  and  measured  by  the  use 
of  prisms,  but  they  do  not  show  the  same  constancy  as  the 
refractive  errors  of  the  eye,  owing  probably  to  the  fact  that  they 
involve  the  variable  factor  of 'muscular  tonus. 

The  principle  used  in  detecting  heterophoria  is  to  produce  a  condition  of 
diplopia  by  placing  prisms  in  front  of  the  eyes.  If,  for  example,  a  prism  (5°) 
is  placed  in  front  of  the  right  eye  with  its  base  up,  the  image  of  any  object 
looked  at,  a  candle-flame,  for  instance,  at  a  distance  of  6  meters,  will  be  dis- 
placed on  the  retina  above  the  fovea  and  will  be  projected,  therefore,  into  the 
lower  half  of  the  visual  field.  The  left  eye  receives  its  image  on  the  fovea  and 
two  flames  are  seen  one  above  the  other,  a  condition  of  vertical  diplopia.  As 
the  images  cannot  be  united  by  movements  of  the  eyeballs  the  eyes  come  to 
rest  in  their  position  of  equilibrium.  If  the  two  flames  lie  in  a  vertical  line  the 
eyes  are  in  balance  for  distant  vision.  If  the  image  belonging  to  the  right 
eye  (in  this  case  the  lower  image)  is  displaced  toward  the  left  hand  as  com- 
pared with  the  other,  exophoria  is  indicated.  The  pull  of  the  external  rectus 
has  thrown  the  front  of  the  eye  toward  the  right  and  its  fovea  in  the  oppo- 
site direction,  hence  the  image  has  fallen  to  the  right  of  the  fovea  and  is  dis- 
placed in  the  visual  field  toward  the  left.  A  deviation  in  the  other  direction 
would  indicate  esophoria,  and  the  amount  in  each  case  is  expressed  by  the  degree 
of  prism  necessary  to  bring  the  objects  into  a  vertical  line  (for  esophoria  the 
correcting  prism  is  placed  base  out,  for  exophoria,  base  in).  In  a  similar  way 
hyperphoria  is  detected  by  producing  in  the  beginning  a  condition  of  lateral 
diplopia,  by  placing  a  suitable  prism  before  the  eye  with  its  base  in.  Several 
systems  of  notation  have  been  proposed  for  prisms.  The  one  commonly  used 
expresses  in  degrees  the  angle  (refracting  angle)  at  the  edge  of  the  prism. 

The  defect  may  be  remedied  by  surgical  operations  upon  the 
muscles,  or  by  the  use  of  proper  prisms  with  their  bases  so  adjusted 
as  to  help  the  weaker  muscle.  In  exophoria,  for  example,  the 
greater  pull  of  the  external  rectus  rotates  the  front  of  the  eye 
outward,  while  the  back  of  the  eye  with  the  fovea  is  moved  inward 
toward  the  nose.  A  prism  of  the  proper  strength  placed  before 
the  eye  with  its  base  in  toward  the  nose  will  throw  the  image  of 
an  external  object  on  the  fovea,  without  necessitating  a  con- 
traction of  the  internal  rectus  to  bring  the  fovea  back  into  its  nor- 
mal position.  When  the  lack  of  balance  between  the  opposing 
muscles  is  so  great  that  the  visual  axes  cannot  by  muscular 
effort  be  brought  to  bear  upon  the  same  points,  we  have  the  condi- 
tion of  squint  or  strabismus.  Such  a  condition  may  result  from 
a  deficiency  in  strength  or  in  actual  paralysis  of  one  or  more  of  the 


372 


THE    SPECIAL    SENSES. 


muscles,  or  from  an  overaction  in  some  of  the  muscles  as  con- 
trasted with  their  antagonists. 

The  Binocular  Field  of  Vision. — When  the  two  eyes  are  fixed 
upon  a  given  point,  placed,  let  us  say,  in  front  of  us  in  the  median 
plane,  each  eye  has  its  own  visual  field  that  may  be  charted 
by  means  of  the  perimeter.  But  the  two  fields  overlap  for  a 
portion  of  their  extent,  and  this  overlapping  area  constitutes 
the  field  of  binocular  vision  (see  Fig.  158).  Every  point  in  the  bin- 
ocular field  forms  an  image  upon  the  two  retinas.  The  most 
interesting  fact  about  the  binocular  field  is  that  some  of  the  objects 


oet    OBI 


Fig.  158. — Perimeter  chart  to  show  the  extent  of  the  binocular  visual  field  (shaded  area) 
when  the  eyes  are  fixed  upon  a  median  point  in  the  horizontal  plane. 

contained  in  it  are  seen  single  in  spite  of  the  fact  that  there  are  two 
retinal  images,  while  others  are  seen  or  may  be  seen  double  when 
one's  attention  is  directed  to  the  fact.  Whether  any  given  object 
is  seen  single  or  double  depends  upon  whether  its  image  does  or  does 
not  fall  upon  corresponding  points  in  the  two  retinas. 

Corresponding  or  Identical  Points. — By  definition  corre- 
sponding or  identical  points  in  the  two  retinas  are  those  which  when 
simultaneously  stimulated  by  the  same  luminous  object  give  us  a 
single  sensation,  while  non-corresponding  points  are  those  which 
when  so  stimulated  give  us  two  visual  sensations.  It  is  evident, 
from  our  experience,  that  the  fovese  form  corresponding  points  or 
areas.  When  we  look  at  any  object  we  so  move  our  eyes  that  the 


BINOCULAR   VISION.  373 

images  of  the  point  observed  shall  fall  upon  symmetrical  parts  of  the 
two  foveae;  the  lines  of  sight  of  the  two  eyes  converge  upon  and 
meet  in  the  point  looked  at.  If,  while  observing  an  object,  we  press 
gently  upon  one  eyeball  with  the  end  of  the  finger,  two  images  are 
seen  at  once,  and  they  diverge  farther  and  farther  from  each  other 
as  the  pressure  upon  the  eyeball  is  increased.  Experiment  shows, 
also,  that,  in  a  general  way,  portions  of  the  retina  symmetrically 
placed  to  the  right  side  of  the  foveae  in  the  two  eyes  are  cor- 
responding, and  the  same  is  true  for  the  two  left  halves  and  the  two 
upper  and  lower  halves.  The  right  half  of  the  retina  in  one  eye  is 
non-corresponding  to  the  left  half  of  the  other  retina,  and  vice 
versa;  and  the  same  relation  is  true  of  the  upper  and  lower  halves, 
respectively.  If  we  imagine  one  retina  to  be  lifted  without  turning 
and  laid  over  the  other  so  that  the  fovese  and  vertical  and  horizontal 
meridians  coincide,  then  the  corresponding  points  will  be  superposed 
throughout  those  portions  of  the  retina  that  represent  the  binocular 
field.  This  statement,  however,  is  theoretical  only ;  an  exact  point 
to  point  correspondence  has  not  been  determined  experimentally. 
Experiments  have  shown,  however,  that  the  corresponding  points 
in  the  upper  halves  of  the  retinas  along  the  vertical  mid-line  do 
not  cover  each  other,  that  is,  they  do  not  lie  in  the  actual  anatom- 
ical vertical  meridian,  but  form  two  meridians  which  diverge 
symmetrically  from  the  mid-line  so  as  to  make  an  angle  of  about 
2  degrees  (physiological  incongruence  of  the  retinas).  Within  the 
limits  of  our  powers  of  observation  for  ordinary  objects  we  may 
adopt  Tscherning's  rule, — namely,  that  when  the  images  of 
an  object  on  the  two  retinas  are  projected  to  the  same  side  of  the 
point  of  fixation  they  are  seen  single,  their  retinal  images  in  this 
case  falling  on  the  retina  to  the  same  side  of  the  lines  of  sight ;  when, 
however,  the  retinal  images  fall  on  opposite  sides  of  the  lines  of 
sight  and  are  projected  to  opposite  sides  of  the  point  of  fixation, 
they  are  seen  double.  The  doubling  of  objects  that  do  not  fall  on 
corresponding  points  (physiological  diplopia)  is  most  readily 
demonstrated  for  objects  that  lie  between  the  lines  of  sight,  either 
closer  or  farther  away  than  the  object  looked  at.  If,  for  instance, 
one  holds  the  two  forefingers  in  front  of  the  face,  in  the  median 
plane,  one  hand  being  at  about  the  near  point  of  distinct  vision 
and  the  other  as  far  away  as  possible,  it  will  be  noticed  that  when 
the  eyes  are  fixed  on  the  far  finger  the  near  one  is  seen  double 
and  vice  versa.  In  this,  as  in  other  experiments  in  which  the  eyes 
are  accommodated  for  one  object  while  the  attention  is  directed 
to  another,  some  difficulty  may  be  experienced  at  first  in  disso- 
ciating these  two  acts  which  normally  go  together,  but  a  little 
practice  will  soon  enable  one  to  distinguish  clearly  the  doubling 
of  the  point  upon  which  the  lines  of  sight  are  not  converged. 


374 


THE    SPECIAL    SENSES. 


If  a  long  stick  is  held  horizontally  in  front  of  the  eyes  the  end 
near  the  face  will  be  doubled  when  the  eyes  are  directed  to  the 
far  end  and  vice  versa.  Moreover,  by  a  simple  experiment  it 
may  be  shown  that  objects  nearer  the  eyes  than  the  point  looked  at 
are  doubled  heteronymously, — that  is,  the  right-hand  image  be- 
longs to  the  left  eye  and  the  left-hand  one  to  the  right  eye.  This  is 
easily  demonstrated  by  closing  the  eyes  alternately  and  noting 
which  of  the  images  disappears.  The  reason  for  the  cross-projec- 
tion of  the  images  is  made  apparent  by  the  construction  in  Fig.  159, 
7,  bearing  in  mind  the  essential  fact  that  in  projecting  our  retinal 
images  we  always  project  to  the  plane  of  the  object  upon  which  the 
eyes  are  focused.  In  the  figure  the  eyes  are  converged  on  A ;  the 
images  of  point  B  fall  to  opposite  sides  of  the  line  of  sight  and  are 
seen  double  and  are  projected  to  the  plane  of  A,  the  image  on  the 
right  eye  being  projected  to  6'  on  the  left  of  A  and  that  on  the  left  eye 
to  6  on  the  right  of  A.  In  a  similar  way  it  may  be  shown  that  ob- 
jects farther  away  from  the  eye  than  the  point  looked  at  are  doubled 
homonymously, — that  is,  the  right-hand  image  belongs  to  the  right 
eye,  and  the  left-hand  one  to  the  left  eye.  The  fact  is  explained  by 
the  construction  in  Fig.  159,  //,  in  which  A  is  the  point  converged 
upon  and  B  the  more  distant  object.  In  all  binocular  vision,  there- 
fore, the  series  of  objects  between  the  eye  and  the  point  looked  at  are 


Fig.  159. — Diagrams  to  show  homonymous  and  heteronymous  diplopia:  In  /  the  eyes 
are  focused  on  A;  the  images  of  B  fall  on  non-corresponding  points, — that  is,  to  different 
sides  of  the  fovese, — and  are  seen  double,  being  projected  to  the  plane  of  A,  giving  heter- 
onymous diplopia.  In  II  the  eyes  are  focused  on  the  nearer  point,  A,  and  the  farther  point, 
B,  forms  images  on  non-corresponding  points  and  is  seen  double, — homonymous  diplopia, 
— the  images  being  projected  to  the  focal  plane  A. 

doubled  heteronymously,  and  those  extending  beyond  the  point  in 
the  same  line  are  doubled  homonymously.  Normally  we  take  no 
conscious  notice  of  this  fact,  our  attention  being  absorbed  by  the 
object  upon  which  the  lines  of  sight  are  directed.  Some  physi- 
ologists, however,  have  assumed  that  the  knowledge  plays  an  im- 
portant part  subconsciously  in  giving  us  an  idea  of  depth  or  per- 
spective,— an  immediate  perception,  as  it  were,  of  the  distinction 


BINOCULAR   VISION.  375 

between  foreground  and  background.  It  is  usually  assumed  that  the 
explanation  of  corresponding  points  is  to  be  found  in  the  anatomical 
arrangement  of  the  optic  nerve  fibers.  Those  from  the  right  halves 
of  the  two  retinas,  which  are  corresponding  halves,  unite  in  the 
right  optic  tract  and  are  distributed  to  the  right  side  of  the  brain, 
while  the  fibers  from  the  left  halves  go  to  the  left  side  of  the  brain. 
The  basis  of  the  single  sensation  from  two  visual  images  is  to  be 
found  probably  in  the  fact  that  the  cerebral  terminations  through 
which  the  final  psychical  act  is  mediated  lie  close  together  or  possibly 
unite. 

The  Horopter. — In  every  fixed  position  of  the  eyes  there  are 
a  certain  number  of  points  in  the  binocular  field  which  fall 
upon  corresponding  points  in  the  two  retinas  and  are  therefore 
seen  single.  The  sum  of  these  points  is  designated  as  the  horopter 
for  that  position  of  the  eyes.  It  may  be  a  straight  or  curved  line, 
or  a  plane  or  curved  surface.  Helmholtz  calls  attention  to  the  fact 
that,  when  standing  with  our  eyes  in  the  primary  position, — that 
is,  directed  toward  the  horizon, — the  horopter  is  a  plane  coinciding 
with  the  ground,  and  this  fact  may  possibly  be  of  service  to  us  in 
walking. 

Suppression  of  Visual  Images. — It  happens  not  infrequently 
that  when  an  image  of  an  object  falls  upon  non-corresponding 
points  in  the  two  retinas  the  mind  ignores  or  suppresses  one  of  the 
images.  This  peculiarity  is  exhibited  especially  in  the  case  of  per- 
sons suffering  from  "squint"  (strabismus).  In  this  condition  the 
individual,  for  one  reason  or  another,  is  unable  to  adjust  the  contrac- 
tions of  his  eye  muscles  so  as  to  unite  his  lines  of  sight  upon  the 
object  looked  at.  The  image  of  the  object  falls  upon  non-corre- 
sponding points  and  should  give  double  vision,  diplopia.  This 
would  undoubtedly  be  the  case  if  the  condition  came  on  suddenly; 
just  as  double  vision  results  when  we  dislocate  one  eyeball  by 
pressing  slightly  upon  it.  But  in  cases  of  long  standing  one  of  the 
images,  that  from  the  abnormal  eye,  is  usually  suppressed.  The 
act  of  suppression  seems  to  be  a  case  of  a  stronger  stimulus  prevail- 
ing over  a  weaker  one  in  consciousness,  just  as  a  painful  sensation 
from  stimulation  of  one  part  of  the  skin  may  be  suppressed  by  a 
stronger  pain  from  some  other  region. 

Struggle  of  the  Visual  Fields. — When  the  images  of  two  dis- 
similar objects  are  thrown,  one  on  each  retina,  the  mind  is  presented, 
so  to  speak,  simultaneously  with  two  different  sensations.  Under 
such  circumstances  what  is  known  as  the  struggle  of  the  visual 
fields  ensues.  If  the  image  on  one  eye  consists  of  vertical  lines 
and  on  the  other  of  horizontal  lines  we  see  only  one  field  at  a  time, 
first  one  then  the  other,  or  the  field  is  broken,  vertical  lines  in  part 
and  horizontal  lines  in  part;  there  is  no  genuine  fusion  into  a  con- 


376  THE    SPECIAL    SENSES. 

tinuous,  constant  picture.  The  struggle  of  the  two  fields  is  better 
illustrated  when  different  colors  are  thrown  on  the  two  retinas. 
When  red  and  yellow  are  superposed  on  one  retina  we  obtain  a  com- 
pound sensation  of  orange;  if  they  are  thrown  one  on  one  retina, 
one  on  the  other,  no  such  fusion  takes  place.  We  see  the  field 
alternately  red  or  yellow  or  a  mixture  of  part  red  and  part  yellow, 
or  at  times  one  color,  as  it  were,  through  the  other.  If,  however, 
one  field  is  white  and  the  other  black  a  peculiar  sensation  of  glitter 
is  obtained,  quite  unlike  the  uniform  gray  that  would  result  if  the 
two  fields  were  superposed  on  one  retina. 

Judgments  of  Solidity. — Our  vision  gives  us  knowledge  not 
only  of  the  surface  area  of  objects,  but  also  of  their  depth  or  solidity, 
— that  is,  from  our  visual  sensations  we  obtain  conceptions  of  the 
three  dimensions  of  space.  The  visual  sensations  upon  which  this 
conception  is  built  are  of  several  different  kinds,  partly  monocular, — 
that  is,  such  as  are  perceived  by  one  eye  alone, — partly  binocular. 
If  we  close  one  eye  and  look  at  a  bit  of  landscape  or  a  solid  object 
we  are  conscious  of  the  perspective,  of  the  right  relations  of  fore- 
ground and  background,  and  those  individuals  who  have  the 
misfortune  to  lose  one  eye  are  still  capable,  under  most  circum- 
stances, of  correct  visual  judgments  concerning  three  dimen- 
sional space.  Nevertheless  it  is  true  that  with  binocular  vision 
our  judgments  of  perspective  are  more  perfect,  and  that  under 
certain  circumstances  data  are  obtained  from  vision  with  two  eyes 
which  give  us  an  idea  of  solidity  far  more  real  than  can  be  obtained 
with  one  eye  alone.  This  difference  is  shown  especially  in  the 
combination  of  stereoscopic  pictures,  and  in  ordinary  vision  when 
the  light  is  dim,  as  in  twilight,  or  in  exact  judgments  of  perspective 
in  the  case  of  objects  close  at  hand.  If,  for  example,  we  close  one 
eye  and  attempt  to  thread  a  needle,  light  a  pipe,  or  make  any  similar 
co-ordinated  movement  that  depends  upon  an  exact  judgment  of 
the  distance  of  the  object  away  from  us,  it  will  be  found  that  the 
resulting  movement  is  far  less  perfectly  performed  than  when  two 
eyes  are  used.  The  sensation  elements  upon  which  our  judgments 
of  depth  or  perspective  are  founded  may  be  classified  as  follows  :* 

The  Monocular  Elements. — That  is,  those  that  are  experienced 
in  vision  with  one  eye.  (a)  Aerial  perspective.  The  air  is  not  en- 
tirely transparent,  and,  therefore,  in  viewing  landscapes  the  more 
distant  objects  are  less  distinctly  seen,  as  is  illustrated,  for  instance, 
by  the  haze  covering  distant  mountains.  This  experience  leads  us 
sometimes  to  make  erroneous  judgments  when  the  conditions  are 
unusual.  An  object  seen  suddenly  in  a  fog  looms  large,  as  the 
expression  goes,  since  the  feeling  that  hazy  objects  are  at  a  great 

*  See  Le  Conte,  "Sight,"  vol.  31  of  "The  International  Scientific  Series," 
1881. 


BINOCULAR   VISION.  377 

distance  leads  us  to  give  a  proportional  overvaluation  to  the  rela- 
tively large  visual  image  made  by  the  near  object. 

(b)  Mathematical   perspective.    The  outlines  of   objects   before 
us  are  projected  upon  the  surface  of  the  eye  in  two  dimensions  only, 
just  as  they  are  represented  in  a  drawing.     The  lines  that  indicate 
depth  are  therefore  foreshortened,  and  lines  really  parallel  tend  to 
converge  more  and  more  to  a  vanishing  point  in  proportion  to  their 
distance  away  from  us.     When  one  stands  between  the  tracks  of  a 
railway,  for  instance,  this  convergence  of  the  parallel  lines  is  dis- 
tinctly apparent.     We  have  learned  to  interpret  this  mathematical 
perspective  correctly  and  with  great  accuracy.    The  use  of  this 
perspective  in  drawings  is,  in  fact,  one  of  the  chief  means  employed 
by  the  artist  to  produce  an  impression  of  depth  or  solidity.     For 
distant  objects  at  least  this  factor  is  probably  the  most  potent  of 
those  that  can  be  appreciated  by  monocular  vision. 

The  importance  of  the  mathematical  perspective  for  our  visual  judgments 
may  be  illustrated  very  strikingly  by  a  simple  experiment.  If  one  takes  a 
biconvex  lens  of  short  focus  and  standing  at  a  window  that  looks  out  upon  a 
long  street  holds  the  lens  in  front  of  the  eyes  at  arm's  length  he  will  be  able 
to  see,  by  focusing  on  the  inverted  image  formed  by  the  lens,  that  not  only 
are  objects  inverted  as  regards  their  surface  features,  but,  for  most  persons 
at  least,  the  perspective  is  also  inverted.  Objects  actually  in  the  foreground 
will  appear  in  the  background,  and  one  may  have  the  curious  sensations  of 
watching  persons  who.  as  they  walk,  seem  to  recede  farther  and  farther  into 
the  distance  in  spite  of  the  fact  that  they  continue  to  increase  in  size.  The 
inverted  or  pseudoscopic  vision  thus  produced  is  due  undoubtedly  to  the  in- 
version of  the  lines  of  perspective.  Parallel  lines  which,  without  the  lens, 
would  have  on  the  retina  a  projection  of  this  kind  /\  are  with  the  lens  projected 
inverted  V,  and  our  visual  judgments  are  controlled  by  this  factor  in  spite 
of  the  opposing  evidence  from  the  size  of  the  retinal  images.  In  order  for 
the  experiment  to  succeed  it  is  necessary  that  the  objects  viewed  shall  be  far 
enough  away  so  that  a  flat  picture  may  be  given  by  the  lens, — that  is,  a  pic- 
ture in  which  the  foci  for  the  near  points  shall  not  differ  practically  from  those 
of  more  distant  points,  otherwise  the  muscular  movements  of  accommodation 
interfere  with  the  delusion.  The  relative  importance  of  this  last  factor 
(see  succeeding  paragraph)  is  well  illustrated  by  varying  the  experiment  in 
this  way:  Place  two  objects  upon  a  well-lighted  table,  one  at  the  near  end 
and  one  at  the  far  end.  Then  standing  close  to  the  table  view  these  objects 
through  the  lens  as  before.  They  will  be  seen  in  their  right  relations  to  each 
other.  If,  however,  one  backs  away  from  the  table  while  watching  the  images 
there  will  come  a  distance  at  which  the  near  object  will  be  seen  to  shift  around 
to  the  rear  of  the  far  object. 

(c)  The  Muscle  Sense  (Focal  Adjustment}. — For  objects  near 
enough  to  require  accommodation  it  is  obvious  that  the  nearer 
object  will  need  a  stronger  contraction  of  the  ciliary  muscle,  and 
also  of  the  internal  rectus  in  order  to  bring  the  line  of  sight  to  bear 
correctly.    By  means  of  the  fibers  of  muscle  sense  we  have  a  verv 
exact  conception  of  the  degree  of  contraction  of  these  muscles,  and 
this  sensation  is  perhaps  the  most  important  factor  used  in  making 
our  monocular  judgments  of  depth  for  objects  at  a  short  distance 


378 


THE    SPECIAL    SENSES. 


In  binocular  vision  the  same  factor  is  doubtless  of  increased  effi- 
ciency by  reason  of  the  sensations  obtained  from  the  two  eyes. 

While  there  is  experimental  evidence  (Sherrington)  that  this  factor  plays 
a  r61e,  it  is  a  fact  that  the  origin  of  the  afferent  fibers  assumed  to  exist  has  not 
been  determined.  Apparently,  they  do  not  come  from  the  fifth  nerve. 

(d)  The  disposition  of  lights  and  shades  and  the  size  of  familiar 
objects.  It  may  be  assumed  that  in  distant  vision  of  complex 
fields  the  varying  lights  and  shades  exhibited  by  objects  according 
as  they  stand  in  front  of  or  behind  each  other  also  aid  our  judg- 
ment. The  actual  size  also  of  the  retinal  images  of  familiar  objects — 
such  as  animals,  trees,  etc. — gives  us  an  accessory  fact  which  con- 
tributes to  the  impression  derived  from  the  sources  mentioned 
above.  These  factors  are  employed  with  effect  by  the  artist  in 
strengthening  the  general  impression  which  he  wishes  to  give  of 
the  difference  between  the  foreground  and  the  background. 

The  Binocular  Perspective. — In  binocular  vision  there  is  an 
additional  element  which  contributes  greatly  to  our  judgment  of 
depth.  This  element  consists  in  the  fact  that  the  retinal  images 
of  external  objects,  particularly  near  objects,  are  different  in  the  two 
eyes.  Inasmuch  as  the  eyes  are  separated  by  some  distance  the 
projection  of  any  solid  object  upon  one  retina  is  different  from 
the  projection  on  the  other.  If  a  truncated  pyramid  is  held  in 
front  of  the  eyes,  the  right  eye  sees  more  of  the  right  side,  the  left 
more  of  the  left  side.  The  projection  of  the  same  object  upon  the 
two  retinas  may,  in  fact,  be  represented  by  the  drawings  given  in 
Fig.  160.  Whenever  this  condition  prevails,  whenever  what  we 
may  call  a  right-eyed  image  of  an  object  is  thrown  on  the  right  eye 
and  simultaneously  a  left-eyed  image  on  the  left  eye,  whether  in 
nature  or  by  an  artifice,  we  at  once  perceive  depth  or  solidity  in  the 
object.  This  fact  is  made  use  of  in  all  devices  employed  to  produce 
stereoscopic  vision. 

Stereoscopic  Vision. — Stereoscopic  pictures  may  be  obtained 

by  photographing  the 
same  object  or  collec- 
tion of  objects  from 
slightly  different 
points  so  as  to  get  a 
right-eyed  and  a  left- 
eyed  picture ;  or  for 
simple  outline  pic- 
tures, such  as  geo- 
metrical figures,  they 


Fig.  160. — Right-  and  left-eyed  images  of  truncated 
pyramid.  May  be  combined  to  produce  solid  image  by 
relaxing  the  accommodation, — that  is,  gazing  to  a  dis- 
tance through  the  book. 


may  be  made  by  draw- 
ings of  the  object  as  seen  by  the  two  eyes,  respectively  (see  Figs. 
160  and  162).  Any  optical  device  that  will  enable  us  to  throw  the 


BINOCULAR   VISION. 


379 


right-eyed  picture  on  the  right  eye  and  the  left-eyed  picture  on 
the  left  eye  constitutes  a  stereoscope.  Many  different  forms  of 
stereoscope  have  been  devised; 

the  one  that  is  most  frequently     A 

used   is  the  Breivster  stereoscope  ;\          \   / 

represented  in  principle  in  Fig. 
161.  Each  eye  views  its  corre- 
sponding picture  through  a 
curved  prism.  The  sight  of  the 
left-eyed  picture  is  cut  off  from 
the  right  eye,  and  vice  versa,  by 
a  partition  extending  for  sbme 
distance  in  the  median  plane. 
The  prisms  are  placed  with  their 
bases  outward  and  the  rays  of 
light  from  the  pictures  are  re- 
fracted, as  shown  in  the  diagram, 
so  as  to  aid  the  eyes  in  converg- 
ing their  lines  of  sight  upon  the 
same  object.  The  prisms  also 
magnify  the  pictures  somewhat. 
Stereoscopic  pictures  are  mounted 
usually  for  this  instrument  so  that 
the  distance  between  the  same 


O.J 


Fig.  161.— Diagram  to  illustrate  the 
principle  of  the  Brewster  stereoscope 
\Landois) :  P  and  P',  the  prisms,  a,  6, 
and  a,  /3,  the  left-  and  ri^ht-eyed  pictures, 
respectively,  6,  ft,  being  a  point  in  the 
foreground  and  a,  a,  a  point  in  the  back- 
ground. The  eyes  are  converged  and 
focused  separately  for  each  point  as  in 
viewing  naturally  an  object  of  three  di- 
mensions. 


object  in  the  two  pictures  is  about  80  mms. — greater,  therefore,  than 
the  interocular  distance.  A  simple  form  of  stereoscope  that  is  very 
effective  and  interesting  is  sold  under  the  name  of  the  anaglyph. 
The  two  pictures  in  this  case  are  approximately  superposed,  but  the 
outlines  of  one  are  in  blue  and  the  other  in  red.  When  looked  at, 
therefore,  the  picture  gives  an  ordinary  flat  view  with  confused 
red-blue  outlines.  If,  however,  one  holds  a  piece  of  red  glass  in 
front  of  the  left  eye  and  apiece  of  blue  glass  in  front  of  the  right  eye, 
or  more  conveniently  uses  the  pair  of  spectacles  provided  which 
have  blue  glass  on  one  side,  red  on  the  other,  then  the  picture  stands 
out  at  once  in  solid  relief  with  surprising  distinctness — and  as  a 
black  and  white  object  only.  The  red  and  blue  glasses  in  this  case 
simply  serve  to  throw  the  right-eyed  image  on  the  right  eye  and  the 
left-eyed  image  on  the  left  eye.  Assuming  that  the  right-eyed 
image  is  outlined  in  red,  then  the  blue  glass  should  be  in  front  of  the 
right  eye.  This  glass  will  absorb  the  red  rays  completely  so  that 
the  red  outlines  in  the  picture  will  seem  black  and  a  distinct  right- 
eyed  picture  is  thrown  on  the  right  eye,  distinct  enough  to  make  us 
overlook  the  much  fainter  image  in  blue,  which  is  also  trans- 
mitted through  the  blue  glass.  The  red  glass  before  the  left 


380 


THE    SPECIAL    SENSES. 


Fig.  162. — Stereoscopic  picture  of  an  octahe- 
dral crystal.  May  be  combined  stereoscopically 
by  relaxing  the  accommodation  by  the  method 
01  heteronymous  diplopia.  Hold  the  object  at  a 
distance  of  a  foot  or  more  and  gaze  beyond. 


eye  cuts  out,  in  the  same  way,  the  right-eyed  image  and  presents 
in  dark  outline  the  left-eyed  image.  By  simply  reversing  the 
spectacles  the  right-eyed  image  may  be  thrown  upon  the  left  eye 
and  vice  versa.  Under  these  conditions  the  picture  for  most  per- 
sons may  be  seen  in  inverted 
relief  (pseudoscopic  vision), 
objects  in  the  foreground  re- 
ceding into  the  background. 
This  inversion  of  the  relief 
when  the  projection  upon  the 
retinas  is  reversed  is  a  strik- 
ing .indication  of  the  potency 
of  the  normal  projection  as  a 
factor  in  our  judgments  of 
solid  objects.  It  will  be  ob- 
served, moreover,  that  those 
pictures  that  show  least 

mathematical  perspective  are  the  most  readily  inverted,  and  that 
the  ability  to  invert  the  picture  varies  in  different  individuals;  in 
some,  what  we  have  called  the  binocular  perspective,  founded  upon 
the  dissimilar  images,  prevails  over  the  mathematical  perspective 
more  readily  than  in  others. 

Stereoscopic  pictures  may  also  be  combined  very  successfully 
without  the  use  of  a  stereoscope  by  virtue  of  the  phenomenon  of 
physiological  diplopia.  If,  for  instance,  two  stereoscopic  drawings, 
such  as  are  represented  in  Fig.  162,  are  held  before  the  eyes  and  one 
relaxes  his  accommodation  so  as  to  look  through  the  pictures,  as  it 
were,  to  a  point  beyond,  then,  in  accordance  with  what  was  stated 
on  p.  373,  each  picture  gives  a  double  image,  since  it  falls  on 
non-corresponding  parts  of  the  two  retinas.  Four  pictures,  there- 
fore will  be  seen,  all  out  of  focus.  With  a  little  practice  one  can  so. 
converge  his  eyes  as  to  make  the  two  middle  images  come  together, 
and  since  one  of  these  is  an  image  of  the  right-eyed  picture  and  is 
falling  on  the  right  eye,  and  the  other  is  a  left-eyed  picture  falling 
on  the  left  eye,  the  combination  of  the  two  fulfills  the  necessary 
conditions  for  binocular  perspective.  The  figure  stands  out  in 
bold  relief. 

Explanation  of  Binocular  Perspective. — Our  perception  of 
solidity  or  relief  is  a  secondary  psychical  act,  and,  so  far  as  the  binoc- 
ular element  is  concerned,  it  is  based  upon  the  fact  that  the  images 
are  slightly  different  on  the  two  retinas;  but  why  this  dissimilarity 
should  produce  an  inference  of  this  kind  is  not  entirely  understood. 
Certain  facts  have  been  pointed  out  as  having  a  probable  bearing 
upon  the  mental  process.  In  the  first  place,  in  stereoscopic  pictures, 


BINOCULAR    VISION.  381 

as  in  nature,  we  do  not  see  the  whole  field  at  once.  To  see  the  ob- 
jects in  the  foreground  the  eyeballs  must  be  converged  by  the  eye 
muscles  so  that  the  lines  of  sight  may  meet  in  the  object  regarded. 
When  attention  is  paid  to  objects  in  the  background  less  convergence 
is  necessary  (see  Fig.  161).  The  point  of  fixation  for  the  lines  of 
sight  is  kept  continually  moving  to  and  fro,  and  the  sensation  of 
this  muscular  movement  possibly  plays  an  important  part  in 
giving  us  the  idea  of  depth  or  solidity.  For  persons  not  practised 
in  the  matter  of  observing  stereoscopic  pictures  the  full  idea  of  relief 
fomes  out  only  after  this  muscular  activity  has  been  called  upon. 
But  for  the  practised  eye  this  play  of  the  muscles  is  not  absolutely 
necessary.  The  stereoscopic  picture  stands  out  in  relief  even  when 
illuminated  momentarily  by  the  light  of  an  electric  spark.  The  per- 
ception of  solidity  in  this  case  is  instantaneous,  and  it  has  been  sug- 
gested that  this  result  may  depend  upon  the  immediate  recognition 
of  physiological  diplopia, — that  is,  the  fact  that  objects  nearer  than 
the  point  of  fixation  are  doubled  heteronymously,  while  those 
farther  away  are  doubled  homonymously  (see  p.  374).  Such  an 
effect  can  only  be  produced  distinctly  by  objects  having  depth 
and  possibly  in  the  case  of  the  trained  eye  it  alone  is  sufficient  to 
give  the  immediate  inference  of  solidity  or  relief,  while  the  un- 
trained eye  requires  the  accessory  sensations  aroused  by  focal 
adjustment,  mathematical  perspective,  etc. 

Judgments  of  Distance  and  Size. — Judgments  of  distance 
and  size  are  closely  related.  Our  judgments  regarding  size  are 
based  primarily  upon  the  size  of  the  retinal  image,  the  amount  of 
the  visual  angle.  This  datum,  however,  is  sufficient  in  itself  only 
for  objects  at  the  same  distance  from  us.  If  they  are  at  different 
distances  or  we  suppose  that  such  is  the  case,  our  judgment  of  the 
distance  controls  our  judgment  of  size.  This  fact  is  beautifully 
shown  in  the  case  of  after-images  (see  p.  352).  When  an  after- 
image of  any  object  is  obtained  on  the  retina  our  judgment  of  its 
size  depends  altogether  on  the  distance  to  which  we  project  it. 
If  we  look  at  a  surface  near  at  hand,  it  seems  small ;  if  we  gaze  at  a 
wall  many  feet  away  it  is  at  once  greatly  enlarged.  The  familiar 
instance  of  the  variation  in  the  size  of  the  full  moon  according  as  it 
is  seen  at  the  horizon  or  at  the  zenith  depends  upon  the  same  fact. 
The  distance  to  the  horizon  as  viewed  along  the  surface  of  the  earth 
seems  greater  than  to  the  zenith ;  we  picture  the  heavens  above  us 
as  an  arched  dome  flattened  at  the  top,  and  hence  the  same  size  of 
retinal  image  is  interpreted  as  larger  when  we  suppose  that  we  see 
it  at  a  greater  distance.  Our  judgments  of  distance,  on  the  other 
hand,  depend  primarily  upon  the  data  already  enumerated  in 
speaking  of  the  perception  of  solidity  or  depth  in  the  visual  field. 


382  THE  SPECIAL  SENSES. 

For  objects  within  the  limit  of  accommodation  we  depend  chiefly 
on  the  muscle  sense  aroused  by  the  act  of  focusing  the  eyes, — that 
is,  the  contractions  of  the  ciliary  and  of  the  extrinsic  muscles.  For 
objects  outside  the  limit  of  accommodation  we  are  influenced  by 
binocular  perspective,  mathematical  perspective,  aerial  perspective, 
etc.  But  here  again  our  judgment  of  distance  is  greatly  influenced 
in  the  case  of  familiar  objects  by  the  size  of  the  retinal  image.  A 
striking  instance  of  the  latter  fact  is  obtained  by  the  use  of  field 
glasses  or  opera  glasses.  When  we  look  through  them  properly 
the  size  of  the  retinal  image  is  enlarged,  and  the  objects,  therefore, 
seem  to  be  nearer  to  us.  If  we  reverse  the  glasses  and  look  through 
the  large  end  the  size  of  the  retinal  image  is  reduced  and  the  objects, 
therefore,  seem  to  be  much  farther  away,  since  under  normal  condi- 
tions such  small  images  of  familiar  objects  are  formed  only  when 
they  are  at  a  great  distance  from  us. 

Optical  Deceptions. — Wrong  judgments  as  regards  distance 
and  size  are  frequently  made  and  the  fact  may  be  illustrated  in  a 
number  of  interesting  ways.  Thus,  in  Fig.  163  the  lines  A  and  B 
are  of  the  same  length,  but  B  seems  to  be  distinctly  the  longer.  So 
in  Fig.  164  the  vertical  lines,  although  exactly  parallel,  seem,  on 
the  contrary,  to  run  obliquely  with  reference  to  one  another.  Both 
of  these  deceptions  depend  apparently  upon  our  inability  to  estimate 
angles  exactly ;  we  undervalue  the  acute  angles  and  overvalue  those 


Fig.   163. — Muller-Lyer  figures  to  show  illusion  in  space  perception.     The  lines  A  and  B 

are  of  the  same  length. 

that  are  obtuse.  A  very  remarkable  delusion  is  given  by  Fig.  165. 
If  the  book  is  held  flat  at  the  level  of  the  chin  and  six  or  eight 
inches  from  the  face  and  the  eyes  are  focused  on  the  point  of 
intersection  of  any  two  of  the  lines,  a  third  line  will  be  seen  per- 
pendicular to  the  plane  of  the  other  two,  and  projecting  vertically 
from  the  surface  of  the  page.  A  row  of  these  vertical  lines  will 
be  seen  if  the  distance  is  properly  chosen.  As  one  bends  the 
head  from  side  to  side  the  lines  sway  in  the  same  direction.  It 
forms  a  very  striking  instance  of  the  fact  that  we  may  see  most 
distinctly  a  thing  that  has  no  real  existence, — a  case,  therefore, 
in  which  we  can  not  trust  our  senses.  The  delusion  seems  to  be 
due  to  the  fact  that  the  two  lines,  in  the  position  indicated,  form 
a  projection  on  the  retina  such  as  would  be  made  by  an  actual 
vertical  rod  placed  at  the  point  at  which  we  see  one.  Fig.  166 
gives  an  interesting  illustration  of  the  way  in  which  our  judg- 


BINOCULAR   VISION. 


383 


ment  of  solidity  may  vary  with  our  interpretation  of  mathe- 
matical perspective  and  shading  when  these  factors  are  arranged 


', 


\\ 
\\ 


\\ 


// 


\  A/ 
\  . 

\ 
\ 

N, 


Jl 

Js 

\\ 
\\ 
\\ 

\\ 

\> 

\\ 

\ 

Fig.  164.— ZSllner's  lines. 


to  give  more  than  one  choice.  If  the  figure  is  looked  at  steadily 
it  may  assume  several  different  appearances;  two  are  especially 
prominent.  We  may  see  two  cubes  resting  upon  a  third  one, 


Fig.  165.— Optical  illusion  in  projection.— (Franklin.') 


each  with  the  black  side  undermost,  or  we  may  see  one  cube  rest- 
ing on  two  under  ones,  each  with  its  black  side  uppermost.    Our 


384  THE  SPECIAL  SENSES. 

judgment  in  the  matter  changes  from  one  interpretation  to  the 
other  without  any  apparent  cause.  That  the  act  of  accommoda- 
tion plays  a  part  in  the  changes  is  shown  by  the  fact  that  if  one 


Fig.  166. — Figure  to  illustrate  binocular  deceptions  depending  upon  different  inter- 
pretations of  the  mathematical  perspective  and  the  lights  and  shades.  On  gazing  fixedly 
the  image  will  change  from  a  single  cube  with  black  top  resting  on  two  others  with  black 
tops,  to  one  of  two  cubes  with  black  bottoms  resting  upon  a  single  cube  with  black 
bottom.  Still  other  figures  may  appear  from  time  to  time. 

focuses  for  the  point  a,  this  point  may  be  held  in  the  foreground 
and  the  second  of  the  above  appearances  be  seen.  While  if  the 
eyes  are  accommodated  strongly  for  point  b,  it  will  be  brought 
forward  and  the  first  of  the  two  appearances  described  is  brought 
into  view. 


PHYSIOLOGY  OF  THE  EAR. 


CHAPTER  XX. 
THE  EAR  AS  AN  ORGAN  FOR  SOUND  SENSATIONS. 

In  discussing  the  physiology  of  the  ear  it  is  necessary  to  consider 
the  functional  importance  of  its  various  parts,  the  external  ear 
consisting  of  the  lobe  or  pinna,  the  external  auditory  meatus,  and 
the  tympanic  membrane;  the  middle  ear,  with  its  chain  of  ossicles, 
its  muscles  and  ligaments,  and  the  Eustachian  tube;  and  the  internal 
ear,  with  its  cochlea,  vestibule  (utriculus  and  sacculus),  and  semi- 
circular canals.  The  eighth  cranial  or  so-called  auditory  nerve  is 


Fig.  167.— Semidiagrammatic  section  through  the  right  ear  (Czermak):  G,  External 
auditory  meatus;  T,  membrana  tympani;  P,  tympanic  cavity;  o,  fenestra  ovalis;  r,  fen- 
estra  rotunda;  B,  semicircular  canal;  S,  cochlea;  Vt,  scala  vestibuli;  Pt,  scala  tympani; 
E,  Eustachian  tube. 

distributed  entirely  within  the  internal  ear;  the  fibers  of  the  coch- 
lear  branch,  which  alone  perhaps  are  concerned  with  hearing,  end 
among  the  sensory  nerve  cells  of  the  cochlea,  while  the  vestibular 
branch  supplies  similar  sense  cells  situated  in  the  utriculus,  sacculus, 
and  the  ampullae  of  the  semicircular  canals.  We  may  consider 
first  the  functions  of  the  ear  in  respect  to  the  sensations  of  sound. 
The  somewhat  complicated  anatomy  of  the  parts  concerned  should 
25  385 


386 


THE    SPECIAL    SENSES. 


be  obtained  from  the  special  works  on  anatomy  or  histology.  Foi 
the  purposes  of  a  physiological  presentation  the  schematic  figure 
employed  by  Czermak  and  reproduced  in  Fig.  167  will  suffice  to 
exhibit  the  general  anatomical  relations  of  the  parts  concerned  in 
the  transmission  of  the  sound  waves  from  the  exterior  to  the  cochlea. 
The  Pinna  or  Auricle. — The  pinna  opens  into  the  external  mea- 
tus by  means  of  a  cone-shaped  depression,  the  concha.  The  whole 
organ,  and  especially  the  concha,  may  be  considered  as  fulfilling 
more  or  less  perfectly  the  function  of  collecting  the  sound  waves 
and  reflecting  them  into  the  meatus.  In  the  lower  animals  the  con- 
cave shape  of  the  ear  and  its  motility  probably  make  it  much  more 
useful  in  this  respect  than  in  the  case  of  the  human  ear.  But  even 
in  man  the  pinna  is  valuable  to  some  extent  in  intensifying  the 

appreciation  of  sounds  and 
also  in  enabling  us  to  deter- 
mine their  direction.  The  ex- 
ternal auditory  meatus  has  a 
length  of  about  21  to  26  mms., 
and  a  capacity  of  something 
over  one  cubic  centimeter. 
Its  course  is  not  straight,  but 
passes  first  somewhat  back- 
ward and  upward,  and  then 
turns  forward  and  inward  to 
end  against  the  tympanic 
membrane.  All  sound  waves 
that  affect  the  drum  of  the  ear 
must,  of  course,  pass  through 
this  canal. 

The  Tympanic  Mem- 
brane.— The  tympanic  mem- 
brane closes  the  inner  end  of 
the  meatus  and  lies  obliquely  to  the  axis  of  the  canal,  its  plane 
making  an  angle,  opening  downward,  of  150  degrees.  The  mem- 
brane, although  not  more  than  0.1  mm.  thick,  consists  of  three 
coats :  a  layer  of  skin  on  the  external  surface,  a  layer  of  mucous 
membrane  on  the  side  toward  the  middle  ear,  and  in  between  a 
layer  of  fibrous  connective  tissue.  The  middle  layer  gives  to  the 
membrane  its  peculiar  structure  and  properties.  In  form  the 
membrane  has  the  shape  of  a  shallow  funnel  with  the  apex,  or 
umbo>  as  it  is  called,  somewhat  below  the  center.  The  fibers  of 
the  fibrous  layer  are  arranged  partly  circularly  and  partly  in  lines 
radiating  from  the  umbo  to  the  peripheral  margin  (Fig.  168). 
The  walls  of  the  funnel  are  slightly  convex  outwardly;  so  that 
each  radiating  fiber  forms  an  arch.  On  the  inner  side  of  the  mem- 
brane the  chain  of  ear  ossicles  is  attached,  so  that  the  vibrations 


168.— To  show  the  structure  of  the 
tympanic  membrane,  looked  at  from  the  side 
of  the  meatus  (Hensen) :  ax,  The  axis  of  rota- 
tion of  the  ear  bones;  d,  the  incus;  a,  the 
head  of  the  malleus. 


EAR    AS    AN    ORGAN    FOR    SOUND    SENSATIONS.  387 

of  the  membrane  are  transmitted  directly  to  these  bones.  The 
peculiar  form  of  the  membrane,  its  funnel  shape,  its  arched  sides, 
and  its  unsymmetrical  division  by  the  umbo  are  supposed  to  con- 
tribute to  its  value  as  a  transmitter  of  the  sound  vibrations  of  the 
air.  In  the  first  place,  the  membrane  shows  little  tendency  to 
after-vibrations,  —that  is,  when  set  in  motion  by  an  air  wave  it 
shows  little  or  no  tendency  to  continue  vibrating  after  the  acting 


Fig.  169. — Tympanum  of  right  side  with  ossicles  in  place,  viewed  from  within  (after 
Morris):  1,  Body  of  incus;  2,  suspensory  ligament  of  malleus;  3,  ligament  of  incus;  4, 
head  of  malleus;  5,  epitym  panic  cavity;  6,  chorda  tympani  nerve;  7,  tendon  of  tensor 
tympani  muscle;  8,  foot-piece  of  stirrup;  9,  os  orbiculare;  10,  manubrium;  11.  tensor 
tympani  muscle;  12,  membrana  tympani:  13,  Eustachian  tube. 

force  has  ceased.  It  is  obvious  that  such  a  property  is  valuable  in 
rendering  hearing  more  distinct,  and  the  peculiarity  of  the  mem- 
brane in  this  respect  is  attributed  partly  to  its  special  form  and 
partly  to  the  damping  action  of  the  bones  attached  to  it.  In  the 
second  place,  the  arched  sides  of  the  funnel  act  as  a  lever,  so  that 
the  movements  at  these  parts  are  transmitted  to  the  umbo  with  a 
diminution  in  amplitude,  but  an  intensification  in  force.  It  is  at 
the  umbo  that  the  movement  is  communicated  to  the  ear  bones. 

The  Ear  Bones.— The  three  ear  bones — the  malleus,  the  incus, 
and  the  stapes — taken  together  form  a  chain  connecting  the  tym- 
panic membrane  with  the  membrane  of  the  fenestra  ovalis.  By 
this  means  the  vibrations  of  the  tympanic  membrane  are  com- 
municated to  the  membrane  of  the  fenestra  ovalis  and  thus  to  the 
perilymph  filling  the  cavity  of  the  internal  ear.  The  bones  consist 


388  THE  SPECIAL  SENSES. 

of  spongy  material  with  a  compact  surface  layer.  Their  general 
shape  and  connections  are  illustrated  in  Figs.  169  and  170.  To 
understand  the  manner  in  which  the  chain  of  bones  acts  in  con- 
veying the  vibrations  from  one  membrane  to  the  other  some  points 
in  their  structure  and  connections  may  be  recalled.  The  malleus 
is  about  8  to  9  mm.  long,  and  has  an  average  weight  of  23  milli- 
grams. Its  long  handle  is  imbedded  in  the  tympanic  membrane, 
the  tip  reaching  to  the  umbo.  The  large,  rounded  head  projects 
above  the  upper  edge  of  the  tympanic  membrane  and  forms  a  true 

joint  of  a  peculiar  nature  with  the 
incus.  It  has  two  processes  in  ad- 
dition to  the  manubrium  :  a  short 
one,  processus  brevis,  that  presses 
against  the  upper  edge  of  the  tym- 
panic membrane,  and  a  longer  one, 
the  processus  gracilis  or  processus 
Folianus,  which  projects  forward 
and  is  continued  by  a  ligament,  the 
anterior  ligament,  through  which 
the  malleus  is  attached  to  the  bony 
wall  of  the  tympanic  cavity.  Three 
other  ligaments  are  attached  to  the 

Fig.    170.—  The    bones    of   the  lt  ,  ,.  J    .  . 

middle  ear  in  natural  connections       malleus,  the  external  ligament  ,  bind- 

(Helmholtz):  M,  The  malleus:  Mcp, 

the  head;     Me,  the  neck;    Ml,  the          mg    it     to   the    external    face  of    the 


cavity,   the  posterior  ligament,  and 
'  long  Pr°cess:   S>       the  superior  ligament,  the  latter  at- 

taching the  upper  part  of  the  head 

to  the  roof  of  the  tympanic  cavity.  By  means  of  these  ligaments 
the  bone  is  held  steadily  in  position  even  after  its  connections 
with  the  incus  are  loosened.  The  incus  is  somewhat  more  mas- 
sive than  the  malleus,  weighing  about  25  milligrams.  Its  thicker 
portion  articulates  with  the  head  of  the  malleus,  and  it  has  two 
processes  nearly  at  right  angles  to  each  other.  The  shorter  process 
extends  posteriorly  and  is  attached  by  a  ligament  to  the  posterior 
wall  of  the  tympanic  cavity;  the  long  process  passes  downward 
parallel  with  the  handle  of  the  malleus,  but  turns  in  at  the  tip 
to  form  the  rounded  os  orbiculare,  which  articulates  with  the 
head  of  the  stapes.  This  latter  bone  is  extremely  light,  weighing 
about  3  milligrams,  its  oval  base  being  attached  to  the  margins 
of  the  fenestra  ovalis  by  a  short,  stiff  membrane. 

The  Mode  of  Action  of  the  Ear  Bones.  —  The  movements  of 
the  tympanic  membrane  are  communicated  to  the  tip  of  the  handle 
of  the  manubrium.  As  the  handle  moves  in,  the  chain  of  bones 
makes  a  rotary  movement  around  an  axis  which  may  be  defined  as 
the  line  passing  through  the  attachment  of  the  short  process  of  the 
incus  and  the  anterior  ligament  of  the  malleus.  The  general  posi- 


EAR    AS    AN    ORGAN    FOR    SOUND    SENSATIONS. 


389 


tion  of  this  axis  is  represented  by  the  line  a-b  in  Fig.  171.  This  line 
passes  through  the  neck  of  the  malleus ;  so  that  as  the  handle  moves 
in  the  head  of  the  malleus  and  the  upper  part  of  the  incus  move  in 
the  opposite  direction, — while  the  long  process  of  the  incus  together 
with  the  stapes,  being  below  the  axis,  moves  in  the  same  direction 
as  the  handle  (see  Fig.  171  A).  The  chain  of  bones,  therefore,  acts 
like  a  bent  lever  whose  fulcrum  is  at  a,  the  power  arm  being  repre- 


Fig.  171.— To  illustrate  the  lever 
action  of  the  ear  bones  (McKendrick) : 
M,  The  malleus;  e,  the  incus;  a-b,  the 
axis  of  rotation:  a,  short  process  of 
incus  abutting  against  the  tympanic 
wall ;  a-p,  the  power  arm ;  a-r.  the 
load  arm  of  the  lever. 


Fig.  171  A. —Schema  to  illustrate  the 
way  in  which  the  ear  ossicles  act  to- 
gether as  a  bent  lever  in  transmitting  the 
movements  of  the  tympanic  membrane 
to  the  membrane  of  the  fenestra  ovalis. 
1,  The  handle  of  the  malleus;  2,  the  long- 
process  of  the  incus;  3,  the  stapes  ;  a-b, 
the  axis  of  rotation.  The  arrows  indi- 
cate a  movement  inward  of  the  tympanic 
membrane. 


sented  by  the  line  p-a  and  the  load  arm  by  the  line  r-a.  According 
to  Helmholtz,*  the  distance  p-a  is  equal  to  9.5  mms.,  while  r-a 
is  6.3  mms.  The  movement  at  r,  therefore,  or  the  movement 
of  the  stapes,  will  have  only  two-thirds  of  the  amplitude  of  the 
movement  at  p,  but  will  *  have  a  correspondingly  greater  force 
(one  and  one-half  times).  The  mechanisms  of  the  tympanic 
membrane  and  the  ear  bones  combine,  therefore,  to  convert  the 
.vibratory  movements  of  the  tympanic  membrane  into  smaller 
but  more  intense  movements  of  the  membrane  of  the  fenestra 
ovalis.  It  should  be  borne  in  mind,  however,  that  the  amplitude 
of  these  movements  under  normal  conditions  is  very  minute. 
That  of  the  base  of  the  stirrup  is  estimated  at  about  0.04 
mm.,  while  the  amplitude  at  the  tip  of  the  manubrium,  though 
relatively  much  larger,  is  still  less  than  a  millimeter  (0.2  to 
0.7  mm.).  The  minute  but  relatively  intense  movements  of  the 
stapes  set  into  vibration  the  perilymph  in  the  internal  ear,  and 
through  these  movements  the  sensory  nerve  cells  in  the  cochlea 

*  Helmholtz,  "Die  Lehre  von  den  Tonempfindungen,  etc.,"  fifth  edition, 
1896.     See  also  English  translation  by  Ellis. 


390  THE    SPECIAL    SENSES. 

are  stimulated,  and  nerve  impulses  are  thereby  aroused  in  the 
fibers  of  the  cochlear  nerve.  Ankylosis  of  the  ear  bones  impedes 
their  movements  and  impairs  the  delicacy  of  hearing,  and  if  the  an- 
kylosis  affects  the  base  of  the  stapes  at  its  insertion  into  the  fenestra 
ovalis  practically  complete  deafness  ensues.  The  articulation  of 
the  head  of  the  malleus  with  the  body  of  the  incus  is  a  peculiar 
saddle-shaped  joint,  which,  according  to  the  description  given  by 
Helmholtz,  acts  like  a  cogged  or  ratchet  movement.  When  the 
tympanic  membrane  moves  in  and  the  head  of  the  malleus,  there- 
fore, moves  outward,  the  joint  locks,  so  that  the  incus  follows  the 
malleus.  If,  however,  from  any  unusual  cause  the  tympanic  mem- 
brane is  moved  outward  from  its  resting  position,  as  may  result,  for 
instance,  from  a  marked  fall  in  air  pressure,  then  the  malleus-incus* 
joint  unlocks  and  the  incus  fails  to  follow  completely  the  movement 
of  the  malleus,  thereby  protecting  the  structures  in  the  internal  ear. 
Muscles  of  the  Middle  Ear. — Two  small  muscles  are  present  in 
the  middle  ear:  the  tensor  tympani  and  the  stapedius.  The  former 
arises  in  a  groove  just  above  the  Eustachian  tube  and  its  long  tendon 
is  inserted  into  the  neck  of  the  malleus  just  below  the  axis  of  rotation. 
The  muscle  is  innervated  by  a  branch  of  the  fifth  nerve.  It  is 
obvious  that  when  this  muscle  contracts  it  must  pull  the  tympanic 
membrane  inward  and  put  it  under  greater  tension.  It  has  been 
shown  that  in  some  persons  this  muscle  can  be  contracted  voluntar- 
ily, the  tympanic  membrane  being  pulled  inward,  f  The  stapedius 
muscle  arises  from  the  inner  wall  of  the  tympanic  cavity  and  its 
tendon  is  inserted  into  the  neck  of  the  stapes.  This  muscle  is 
innervated  through  a  branch  of  the  facial.  When  it  contracts  it 
tends  to  pull  the  stapes  laterally,  and  thus  probably  places  the  mem- 
brane attached  to  its  base  under  greater  tension.  The  functions 
fulfilled  by  these  muscles  have  been  the  subject  of  much  controversy. 
According  to  a  view  first  proposed  by  Johannes  Miiller,  they  act  as 
a  protective  mechanism  to  the  membranes  of  the  middle  ear.  By 
increasing  the  tension  of  the  membranes  they  limit  the  amplitude  of 
their  vibrations  and  thus  protect  the  membranes  from  injury  or 
possible  rupture  in  the  case  of  the  violent  movements  resulting  from 
loud,  explosive  noises.  Or  possibly  by  their  reflex  contraction 
they  protect  us  from  intense,  disagreeable  noises,  by  limiting  the 
responsiveness  of  the  vibrating  membranes.  A  more  probable  view, 
however,  and  one  supported  to  some  extent  by  experimental  evi- 
dence, was  suggested  by  Mach.  According  to  this  observer,  the 
contractions  of  the  muscles  adjust  the  membranes  to  the  better 

*  Some  doubt  has  been  thrown  upon  this  interesting  hypothesis  regarding 
the  nature  of  the  malleus-incus  articulation.  According  to  Frey  ("Pfliiger's 
Archiv,  1911,  139,  548"),  the  two  bones  are  not  united  by  a  true  joint,  but 
are  ankylosed  more  or  less  rigidly,  so  that  movement  between  them  is  not 
probable. 

t  Mangold,  "Pfliiger's  Archiv,"  149,  539,  1913. 


EAR    AS    AN    ORGAN    FOR    SOUND    SENSATIONS.  391 

reception  of  sound  vibrations  and  are  used,  therefore,  in  attentive 
listening.  They  form,  in  fact,  a  mechanism  of  accommodation  simi- 
lar in  its  general  functions  to  the  ciliary  muscle  of  the  eye.  Hensen* 
has  shown  that  both  muscles  contract  reflexly  to  sounds,  and  that 
the  contractions  of  the  tensor  tympani  are  stronger,  the  higher  the 
pitch  of  the  sound.  This  contraction  seems  to  take  place  at  the 
beginning  of  the  sound,  but  is  not  maintained  for  a  long  period. 
The  reaction  is  apparently  a  reflex  movement  the  sensory  path  of 
which  lies  in  the  acoustic  nerve  and  the  reflex  center  in  the  medulla 
oblongata.  That  a  similar  reflex  adjustment  takes  place  in  man  is 
indicated  by  the  following  experiment  described  by  Hensen.  If 
while  listening  to  a  tuning-fork  (400  to  1000  v.  d.)  a  metronome  is  set 
going  at  a  rate  of  40  to  60  beats  per  minute,  the  tone  of  the  tuning- 
fork  becomes  obviously  strengthened.  The  stimulus  of  the  noise 
caused  by  the  metronome  may  be  supposed  to  excite  the  reflex  con- 
tractions of  the  muscles  of  the  ear  and  thus  increase  its  responsive- 
ness to  the  vibrations  of  the  tuning-fork.  According  to  this  view, 
therefore,  the  ear  muscles  are  kept  constantly  in  play  by  sounds  or 
sudden  variations  in  the  intensity  of  sounds,  and  perhaps  the  obvious 
effort  experienced  in  listening  intently  to  a  sound  is  also  due  to  a  con- 
traction of  these  muscles. 

The  Eustachian  Tube. — Through  the  Eustachian  tube  a  com- 
munication is  established  between  the  tympanic  cavity  and  the 
pharynx,  and  through  this  latter  with  the  exterior.  The  obvious 
advantage  of  this  arrangement  is  that  it  keeps  the  air  within  the 
tympanum  under  the  same  pressure  as  the  outside  air, — that  is,  the 
pressure  on  the  two  sides  of  the  tympanic  membrane  is  kept  the 
same.  The  pharyngeal  opening  of  the  tube  is  normally  closed,  but  it 
may  be  opened  by  raising  or  lowering  the  pressure  in  the  pharynx. 
This  happens,  for  instance,  in  the  act  of  swallowing,  and  we  perform 
this  act,  therefore,  whenever  our  sensations  from  the  tympanic  mem- 
brane warn  us  of  an  inequality  in  pressure  upon  the  two  sides.  When, 
for  instance,  one  enters  a  caisson  in  which  the  external  pressure  is 
increased  over  the  normal  atmospheric  pressure  the  tympanic 
membrane  would  be  driven  inward  by  the  excess  of  external  pres- 
sure were  it  not  for  the  existence  of  the  Eustachian  tube.  Under 
these  conditions  swallowing  movements  will  open  the  pharyngeal  end 
of  the  tube  and  thus  bring  the  tympanic  cavity  under  a  barometric 
pressure  equal  to  that  on  the  outside.  In  nasal  catarrh  the  tube 
may  be  occluded  so  as  to  prevent  this  equalization,  and  under  such 
conditions,  as  is  well  known,  the  delicacy  of  hearing  is  much  im- 
paired, until  by  raising  the  pressure  in  the  pharynx  or  by  other 
means  the  tube  is  opened. 

The  Projection  of  the  Auditory  Sensations. — Auditory  sen- 
sations are  projected  to  the  exterior  and,  indeed,  to  the  supposed 
*  Hensen,  "Archiv  f.  d.  gesammte  Physiologic,"  87,  355,  1901. 


392  THE    SPECIAL    SENSES. 

origin  of  the  sound.  The  projection,  however,  is  nothing  like  so 
perfect  as  in  the  case  of  visual  stimuli.  Our  judgments  of  the  dis- 
tance and  direction  of  sounds  are  manifestly  less  exact  than  in  the 
case  of  objects  seen  by  the  eye.  As  an  example,  one  may  refer  to 
the  difficulty  of  locating  exactly  such  sounds  as  the  note  of  a  cricket. 
In  the  ear  the  sensitive  elements  in  the  cochlea  are  not  arranged  so 
that  sounds  coming  from  different  directions  can  affect  different 
nerve  fibers.  All  sound  stimuli  come  to  this  part  of  the  ear  by  one 
path, — namely,  the  tympanic  membrane  and  its  accessory  struc- 
tures. In  judging  the  direction  and  distance  of  sounds  we  must 
rely,  therefore,  upon  the  relative  distinctness  of  the  sounds  in  the 
two  ears,  the  variations  in  distinctness  observed  by  varying  the 
position  of  the  head,  the  accessory  information  obtained  from 
vision,  etc.  It  is  stated  (Brown)  that  when  the  two  ears  are  used, 
the  localization  is  more  exact  than  when  only  one  ear  is  open. 
The  two  ears  act  somewhat  like  the  two  eyes  in  giving  a  spatial 
or  perspective  element  to  the  projection.  The  general  sensibility 
of  the  tympanic  membrane  also  plays  a  part.  When  a  vibrating 
body — a  tuning-fork,  for  example— is  held  between  the  teeth,  the 
vibrations  are  transmitted  to  the  internal  ear,  in  part  at  least, 
through  the  bones  of  the  head,  and  the  sound  in  this  case  is  referred 
or  projected  into  the  head  .itself  instead  of  to  the  tuning-fork,  so 
that  in  hearing  by  the  usual  method  the  sensations  of  the  vibrating 
tympanic  membrane  must  form  part  of  the  data  by  means  of  which 
we  project  the  sensation  to  the  exterior. 

The  Sensdry  Epithelium  of  the  Cochlea.— The  fibers  of  the 
cochlear  branch  of  the  auditory  nerve  arise  in  the  nerve  cells  of  the 
spiral  ganglion  situated  in  the  central  pillar,  the  modiolus,  of  the 
cochlea.  This  ganglion  resembles  in  structure  the  posterior  root 
ganglion  of  the  spinal  nerves.  Each  cell  is  bipolar,  sending  one 
fiber  toward  the  brain  in  the  acoustic  nerve,  and  one  fiber  to  end  in 
terminal  arborizations  around  the  sensory  cells  or  hair  cells  of  the 
organ  of  Corti  in  the  cochlea.  We  have  every  reason  to  believe, 
therefore,  that  these  hair  cells  form  the  apparatus  which  is  affected 
by  sound  and  by  means  of  which  nerve  impulses  are  generated 
and  transmitted  to  the  acoustic  fibers.  The  general  arrangement 
and  the  relations  of  these  cells  are  indicated  in  Fig.  172.  They 
consist  of  short  more  or  less  cylindrical  cells  (E,  6,  6',  6",  Fig.  172), 
whose  lower  portion  does  not  reach  to  the  basilar  membrane,  but 
is  supported  by  the  intervening  Deiters  cells.  The  upper  ends  of 
the  cells  project  through  the  openings  in  the  reticulate  membrane 
and  end  in  a  number — according  to  Retzius,*  about  twenty — short, 
stiff  hairs.  The  hair  cells  are  arranged  in  four  to  six  rows,  one 
row  on  the  inner  side  of  the  inner  rods  of  Corti  and  three  to  five 

*  The  most  complete  details  of  the  structure  of  the  ear  will  be  found  in 
the  great  work  of  Retzius,  "  De  Gehororgan  der  Wirbelthiere,"  vol.  ii,  1884, 
Stockholm. 


EAR  AS  AN  ORGAN  FOR  SOUND  SENSATIONS. 


393 


rows,  according  to  the  part  of  the  cochlea  examined  on  the  outer 
side  of  the  rods  of  Corti.  Their  total  number  has  been  estimated 
differently  by  different  observers;  but,  accepting  the  lower  figures 
given,  it  may  be  said  that  there  are  at  least  3500  inner  hair  cells 
and  13,000  outer  ones,  giving  a  total  of  16,500  or  more.  The  theory 
usually  proposed  to  account  for  the  mechanism  by  which  the  vibra- 
tions of  the  perilymph  affect  these  cells,  and  especially  the  expla- 
nation of  the  means  by  which  different  sounds  affect  different  cells, 
is  that  there  is  contained  in  the  cochlea  a  mechanism  which  acts 
by  sympathetic  resonance.  To  make  this  theory  clear  a  short 


Fig.  172. — Diagrammatic  view  of  the  organ  of  Corti,  the  sense  cells,  and  the  accessory 
structures  of  the  membranous  cochlea  (Testuf) :  A,  Inner  rods  of  Corti ;  B,  outer  rods 
of  Corti  ;  C,  tunnel  of  Corti  ;  D,  basilar  membrane;  E,  single  row  of  inner  nair  (sense) 
cells;  6,  6',  6",  rows  of  outer  hair  (sense)  cells;  7,  7',  supporting  cells  of  Deiters.  The 
ends  of  the  inner  hair  cells  are  seen  projecting  through  the  openings  of  the  reticulate 
membrane.  The  terminal  arborizations  of  the  cochlear  nerve  fibers  end  around  the 
inner  and  outer  hair  cells. 

description  must  be  given  of  the  nature  of  sound  waves  and  the 
physical  facts  in  regard  to  sympathetic  resonance. 

The  Nature  and  Action  of  Sound  Waves. — Sound  waves  in 
air  consist  of  longitudinal  vibrations  of  the  air  molecules,  alternate 
phases  of  rarefaction  and  condensation.  For  convenience'  sake, 
these  waves  are  usually  represented  graphically  after  the  manner  of 
water  waves,  by  a  curved  line  rising  above  and  falling  below  a 
median  zero  line,  the  ordinates  above  the  zero  line  representing 
the  phase  of  condensation,  and  those  below  the  phase  of  rarefaction. 
These  waves  are  produced  by  the  vibrations  of  the  sounding  body, 
and  may  vary  greatly  in  length,  in  amplitude,  and  in  form.  For 
musical  sounds  within  the  range  of  hearing  the  length  of  the  waves 
may  vary  from  forty  to  seventy  feet,  at  the  one  extreme,  to  a  frac- 


394 


THE    SPECIAL    SENSES. 


tion  of  an  inch  at  the  other.  They  travel  through  the  air  with  an 
average  velocity  of  1100  to  1200  feet  per  second,  the  exact  rate  vary- 
ing with  the  temperature.  When  these  waves,  whatever  may  be 
their  form,  follow  each  other  with  regularity — that  is,  with  a  definite 
period  or  rhythm — a  musical  sound  is  perceived  provided  the 
rhythm  is  maintained  for  a  number  of  vibrations.  So  that  regular- 
ity or  periodicity  of  the  sound  waves  may  be  considered  as  the  un- 
derlying physical  cause  of  musical  sounds.  Non-musical  sounds  or 
noises,  which  constitute  the  vast  majority  of  our  auditory  sensa- 
tions, are  referred,  on  the  contrary,  to  non-periodical  vibrations. 
Waves  of  this  kind  may  be  due  to  the  nature  of  the  impulse  given 
to  the  air  by  the  sounding  body, — single  pulses,  for  instance,  or  a 
series  of  such  pulses  or  shocks  following  at  a  slow  or  irregular 
rhythm,  or  as  is  more  frequently  the  case,  they  may  result  from  a 
mixture  of  very  short  and  different  rhythmical  vibrations.  As 
the  case  of  musical  sounds  is  far  the  simpler,  the  theory  of  the 
action  of  the  cochlea  has  been  based  chiefly  upon  the  results 
obtained  from  a  study  of  these  forms  of  waves. 

Classification  and  Properties  of  Musical  Sounds. — Musical 
sounds  exhibit  three  fundamental  properties,  each  of  which  may  be 
referred  to  a  difference  in  the  physical  stimulus.  They  vary,  in 
the  first  place,  in  pitch,  and  this  difference  finds  its  explanation  in 
the  rapidity  of  vibration  of  the  sounding  body  and  the  sound  waves 
produced  by  it.  The  more  rapid  the  rate,  the  shorter  will  be  the 
waves  and  the  higher  will  be  the  pitch  of  the  musical  note.  Notes 
of  the  same  pitch  may,  however,  vary  in  loudness  or  intensity,  and 


Fig.  173. — To  illustrate  the  conception  of  differences  in  pitch  and  in  amplitude  or  intensity: 
In  A  three  pendular  or  sinus  curves  of  the  same  period  or  pitch,  but  with  different  amplitudes. 
In  B  three  pendular  or  sinus  curves  of  the  same  amplitude,  but  with  different  periods  (after 
Auerbach) . 

this  difference  is  referable  to  the  amplitude  of  the  vibrations  (see 
Fig.  173).  A  given  tuning-fork  emits  always  a  note  of  the  same 
pitch,  but  the  loudness  of  the  note  may  vary  according  to  the  amp- 
litude of  the  vibrations.  The  vibrations  of  the  tympanic  mem- 
brane and  of  the  perilymph  in  the  internal  ear  vary  in  rate  and  in- 
tensity with  the  sounding  body;  so  that  we  may  say  that  the  stimu- 
lation of  the  hair-cells  in  the  cochlea  gives  us  auditory  sensations 


EAR    AS    AN    ORGAN    FOR    SOUND    SENSATIONS.  395 

that  vary  in  pitch  with  the  rate  of  excitation  and  in  intensity  with 
the  amplitude  of  the  vibratory  movement.  A  third  property  of 
musical  sounds  is  their  variations  in  quality  or  timbre.  The  same 
note  of  the  same  amplitude,  when  given  by  different  musical  instru- 
ments, varies  in  quality,  so  that  we  have  no  difficulty  in  recognizing 
the  note  of  a  piano  from  the  same  note  when  given  by  a  violin  or 
the  human  voice.  The  underlying  physical  cause  of  variations  in 
timbre  is  found  in  the  form  of  the  sound  waves  produced,  and  im- 
mediately, therefore,  in  the  form  of  vibratory  movement  communi- 
cated to  the  perilymph.  Examination  of  the  forms  of  sound  waves 
produced  by  different  musical  instruments  shows  that  they  may  be 
divided  into  two  great  groups :  (1)  The  simple  or  pendular  form ;  (2) 
the  compound  or  non-pendular  form.  The  simple  or  pendular  form 
of  wave  is  given,  for  instance,  by  tuning  forks.  A  graphic  repre- 
sentation of  this  wave  form  may  be  obtained  by  attaching  a  bristle 
to  the  end  of  the  fork  and  allowing  it  to  write  upon  a  piece  of  black- 
ened paper  moving  with  uniform  velocity, — the  blackened  surface, 
for  instance,  of  a  kymographion.  The  form  of  the  wave  obtained 
is  represented  in  Fig.  174.  The  vibrating  body  swings  symmetrically 
to  each  side  of  the  line  of  rest,  and,  inasmuch  as  this  is  also  the  form 
of  movement  that  would  be  traced  by  a  swinging  pendulum,  this 
form  of  wave  is  designated  frequently  as  pendular.  It  is  sometimes 
called  also  the  sinusoidal  wave,  since  the  distance  of  the  vibrating 
point  to  each  side  of  the  line  of  rest  is  equal  to  the  sine  of  an  arc 
increasing  proportionally  for  the  time  of  the  phase.  A  compound 
(or  non-pendular  or  non-sinusoidal)  wave  may  have  a  very  great 
variety  of  forms.  The  different  phases  follow  periodically,  but  the 
movement  of  the  vibrating  body  to  each  side  of  the  line  of  rest  is  not 


Fig.  174. — Form  of  wave  made  by  tuning  fork. 

perfectly  symmetrical.  Fourier  has  shown  that  any  periodical  vibra- 
cory  movement,  whatever  may  be  its  form,  may  be  considered  as 
being  composed  of  a  series  of  simple  or  pendular  movements  whose 
periods  of  vibrations  are  1,  2,  3,  4,  etc.,  times  as  great  as  the  vibra- 
tion period  of  the  given  movement.  That  is,  every  so-called  com- 
pound wave  form  may  be  considered  as  being  caused  by  the  fusion 
of  a  number  of  simple  waves.  Representing  the  wave  movement 
of  the  air  graphically  as  water  waves,  this  composition  of  simple 
waves  into  compound  ones  is  illustrated  by  the  curves  given  in  Fig. 
175.  In  this  figure  A  and  B  represent  two  simple  vibrations  such 
as  would  be  given  by  two  tuning-forks,  the  vibrations  in  B  being 
double  those  of  A.  If  these  two  waves  are  communicated  to  the  air 


396 


THE    SPECIAL    SENSES. 


at  the  same  time  the  actual  movement  of  the  molecules  will  be  a 
resultant  of  the  forces  acting  upon  them  at  any  given  instant,  and 
will  be  indicated,  therefore,  by  the  algebraical  sum  of  the  ordinates 
above  and  below  the  lines  of  rest.  If  the  movements  are  so  timed 
that  e  in  curve  B  is  synchronous  with  d°  in  curve  A,  then  the 
resulting  compound  wave  form  is  illustrated  by  C.  If,  how- 
ever, curve  B  is  supposed  to  be  in  a  different  phase,  so  that  e 
is  synchronous  with  d',  then  a  form  of  wave  illustrated  by  D  will  be 
obtained.  In  this  way  a  great  variety  of  forms  of  compound  waves 
may  be  supposed  to  be  produced  by  the  union  of  a  series  of  simple 
waves  of  different  periods  of  vibration.  That  compound  waves  dif- 
fer from  simple  ones  in  being  composed  of  several  series  of  vibrations 
is  indicated  directly  by  our  sensations.  When  we  listen  to  the  note 
of  a  tuning-fork  we  hear  only  a  single  tone;  when  two  or  more 
tuning-forks  are  sounded  together  the  trained  ear  can  detect  the  tone 
due  to  each  fork,  and  similarly  when  a  single  note  is  sounded  by 
the  human  voice,  a  violin,  or  any  other  instrument  that  has  a  char- 
acteristic quality  the  trained  ear  can  detect  a  series  of  higher  tones, 


Fig.  175. — Schema  by  Helmholtz  to  illustrate  the  formation  of  a  compound  wave 
from  two  pendular  waves:  A  and  B,  pendular  vibrations,  B  being  the  octave  of  A.  If 
superposed  so  that  e  coincides  with  d°  and  the  ordinates  are  added  algebraically,  the  non- 
pendular  curve  C  is  produced.  If  superposed  so  that  e  coincides  with  d'  the  non-pendular 
curve  D  is  produced. 

the  upper  partial  tones,  or  harmonics,  or  overtones,  which  indicate 
that  the  note  is  really  compound,  and  not  simple.  The  formation 
of  these  overtones  is  due  to  the  fact  that  the  sounding  body  may  be 
considered  as  vibrating  not  only  as  a  whole,  but  also  in  its  aliquot 


EAR    AS    AN    ORGAN    FOR    SOUND    SENSATIONS. 


397 


parts,  as  is  represented  in  Fig.  176,  illustrating  the  vibrations  of  a 
string.  When  the  string  is  plucked,  it  vibrates  as  a  whole  (a),  giv- 
ing large  waves  which  produce  what  is  called  the  fundamental  tone, 
but  at  the  same  time  each  half  (6),  third  (c),  fourth  (d),  etc.,  may 
vibrate,  giving  each  its  own  simple  tone.  The  combination  of  all 
of  these  simple  waves  forms  a  compound  wave  whose  form  or,  at 
least,  whose  composition,  determines  the  quality  of  the  tone  heard. 
As  many  as  ten  or  sixteen  of  these  overtones  may  be  detected  from 
the  vibrating  strings  of  a  violin  or  guitar.  When  the  period  of 
vibration  of  these  overtones  bears  a  simple  ratio  to  that  of  the 
fundamental,  a  ratio  that  can  be  expressed  by  the  simple  num- 


Fig.  176.— To  illustrate  the  mechanism  of  the  formation  of  overtones.— (HdmhoUz.) 
In  o  the  string  vibrates  as  a  whole,  giving  its  fundamental  tone;  in  6,  c,  and  d,  its  halves, 
thirds,  and  fourths  are  vibrating  independently.  When  a  string  is  struck,  plucked,  or  bowed 
these  movements  may  happen  simultaneously  and  the  fundamental  note  due  t9  the  vibra- 
tions of  the  whole  string  is  combined  with  the  notes  due  to  the  vibrations  of  aliquot  parts, 
the  overtones.  The  combination  gives  a  compound  wave  whose  form  and  musical  quality 
vary  with  the  number  and  relative  strength  of  the  overtones. 


bers  1,  2,  3,  4,  5,  they  harmonize  with  it  and  form  the  harmonic 
overtones.  It  should  be  borne  in  mind  that,  so  far  as  the  tympanic 
membrane  is  concerned,  it  does  not  respond  separately  to  the  single 
tones  which  constitute  the  compound  wave,  but  swings  in  unison 
with  the  movement  of  the  compound  wave.  Nevertheless,  the  in- 
ternal ear,  according  to  the  law  of  Ohm,  is  capable  of  analyzing  the 
compound  wave  form  into  the  series  of  simple  or  pendular  wave 
forms  of  which  it  is  composed,  and  of  distinguishing  the  series  of 
corresponding  tones.  While  this  analysis  cannot  be  made  con- 
sciously except  by  the  trained  musician,  it  is  made  unconsciously, 
as  it  were,  by  every  normal  ear,  and  in  consequence  of  this  analysis 


398  THE    SPECIAL    SENSES. 

we  recognize  the  variations  in  quality  of  different  compound  tones. 
The  principle  upon  which  the  cochlea  acts  in  thus  separating  the 
compound  tones  into  their  elements  is  not  explained  with  entire 
satisfaction.  According  to  the  view  so  admirably  presented  by 
Helmholtz,*  the  analysis  depends  upon  the  existence  in  the  ear  of 
a  mechanism  for  sympathetic  vibrations  or  resonance. 

Sympathetic  Vibrations  or  Resonance. — By  sympathetic 
vibration  is  meant  the  fact  that  an  elastic  body  is  easily  set  into 
vibration  by  movements  of  the  surrounding  medium  when  these 
movements  correspond  with  its  own  period  of  vibration.  A  string 
whose  period  of  vibration  is  128  per  second  will  be  little  affected 
by  vibrations  of  the  surrounding  air  unless  they  have  the  same 
periodicity.  If,  however,  a  note  of  this  period  is  sounded  by  the 
voice,  for  instance,  the  string  will  be  set  into  vibration  with  rela- 
tive ease.  By  means  of  this  principle  the  untrained  ear  can  readily 
pick  out  the  more  prominent  of  the  upper  harmonics  of  any  given 
note  of  a  musical  instrument.  It  is  only  necessary  to  select  a  series  of 
resonators  corresponding  to  the  series  of  overtones.  Each  reso- 
nator is  set  into  vibration  by  its  corresponding  overtone  and  so 
emphasizes  this  particular  tone  that  it  may  be  easily  recognized. 
If  one  stands  in  front  of  a  piano  with  the  strings  exposed  and 
sings  a  given  note  it  may  be  shown  that  a  series  of  the  piano  strings 
is  set  into  vibration  corresponding,  in  the  first  place,  to  the  rate 
of  vibration  of  the  fundamental  tone,  and  secondly  to  the  more 
prominent  of  the  harmonic  overtones.  In  this  case  the  com- 
pound wave  strikes  upon  the  collection  of  strings  of  the  piano, 
and  is  analyzed  into  its  component  simple  tones  by  the  sympa- 
thetic vibrations  of  the  corresponding  strings.  Helmholtz  assumes 
that  the  cochlea  analyzes  compound  musical  waves  by  an  essentially 
similar  method. 

The  Functions  of  the  Cochlea. — The  vibratory  movement, 
whatever  may  be  its  form,  in  the  air  of  the  external  meatus  im- 
parts to  the  tympanic  membrane  a  similar  form  of  movement,  and 
this,  in  turn,  through  the  ear  bones  and  the  membrane  of  the  fenes- 
tra  ovalis  sets  the  perilymph  into  vibrations  of  the  same  form.  That 
the  perilymph  can  swing  or  vibrate  under  the  influence  of  the  move- 
ments of  the  stapes  is  explained  by  the  existence  of  the  second 
opening,  the  fenestra  rotunda,  between  the  middle  and  the  inter- 
nal ear  (see  Fig.  167).  As  the  membrane  of  the  fenestra  ovalis  is 
pushed  in,  that  of  the  fenestra  rotunda  is  pushed  out,  and  vice 
versa,  and  the  wave  movement  is  transmitted  along  the  perilymph 
of  the  cochlea  in  a  manner  illustrated  by  the  schema  represented 
in  Fig.  177.  These  vibratory  movements  of  the  perilymph  affect 
the  membranous  cochlea,  which  may  be  regarded  as  being  sus- 
pended in  the  perilymph,  and,  according  to  the  resonance  theory, 
*  Helmholtz,  loc.  cit. 


EAR    AS    AN    ORGAN    FOR    SOUND    SENSATIONS.  399 

certain  structures  within  the  membranous  cochlea  are  set  into  sym- 
pathetic vibrations  corresponding  to  the  simple  waves  of  which  the 
compound  wave  is  constituted.  Helmholtz  first  suggested  that 
the  peculiar  rods  of  Corti  form  the  resonating  apparatus,  and 
by  sympathetic  vibrations  are  capable  of  analyzing  the  compound 

Fertesfra  ^__^  _^ 

\helicotrefna. 


FenesTra  rofancla,~m.  Jcalci 


Fig.  177.  —  Schematic  figure  from  Auerbach  to  show  the  relative  positions  of  the  mem- 
branes of  the  oval  and  round  fenestras  and  the  course  of  the  wave  movement  through  the 
cochlea  from  one  to  the  other. 

movement.  Later,  however,  this  suggestion  was  abandoned, 
since  the  number  of  the  rods  is  not  sufficiently  great  perhaps  to 
answer  the  requirements  of  this  theory.  According  to  Retzius, 
the  inner  rods  number  5600  and  the  outer  ones  3850.  Moreover, 
these  structures  are  absent  from  the  bird's  cochlea,  and  we  must 
assume  that  these  animals  are  capable  of  appreciating  musical 
sounds.  Helmholtz  then  adopted  a  suggestion  of  Hensen's,  that 
the  basilar  membrane  constitutes  the  resonating  apparatus.  This 
membrane  forms  the  floor  of  the  membranous  cochlea,  stretching 
from  the  limbus  to  the  opposite  side  of  the  bony  cochlea  (Fig. 
172).  Its  middle  layer  consists  of  fibers,  running  radially,  which, 
though  united  to  one  another,  are  sufficiently  independent  to  be 
regarded  as  separate  strings.  These  fibers  in  the  portion  covered 
by  the  rods  of  Corti,  the  inner  zone  or  zona  tecta,  are  finer  and 
more  difficult  to  separate  than  in  the  portion  exterior  to  the  outer 
rods,  the  outer  zone  or  zona  pectinata.  From  the  base  to  the  apex 
of  the  cochlea  the  membrane  increases  in  width,  the  length  of  the 
strings  in  the  outer  zone  varying,  according  to  Retzius,  from  135  p.  in 
the  basal  portion  to  220  //  in  the  middle  spiral  and  to  234  fJ.  at  the 
apex.  The  whole  structure  is  estimated  to  contain  about  24,000 
strings  varying  gradually  in  length,  as  stated,  and  resembling  in 
general  arrangement  the  strings  of  the  piano.  Assuming  that  each 
of  these  fibers  has  its  own  period  of  vibration,  we  may  imagine  that 
the  entire  collection  forms  an  apparatus  for  sympathetic  vibration 
which  is  capable  of  analyzing  each  compound  wave  motion  into 
its  constituent  simple  waves,  each  string  being  set  into  strong- 
est vibrations  by  the  wave  of  the  corresponding  period.  More- 
over, it  is  implied  or  assumed  hi  this  theory  that  the  vibrations  of 
each  string  are  communicated  to  a  corresponding  nerve  fiber  of 
the  cochlear  nerve,  through  which  the  stimulus  is  conveyed  to 
the  brain  as  a  nerve  impulse.  We  should  be  capable  of  perceiv- 
ing, theoretically,  as  many  distinct  musical  tones  as  there  are 
fibers  in  the  basilar  membrane,  while  a  compound  wave,  by  setting 
a  number  of  these  mechanisms  into  action,  gives  a  series 
of  sensations  which  are  more  or  less  fused  in  consciousness.  The 


400  THE    SPECIAL    SENSES. 

peculiar  quality  or  timbre  of  the  tone  of  each  instrument  is  refer- 
able, therefore,  immediately  to  the  number  and  relative  intensities 
of  the  simple  tone  sensations  that  it  arouses.  The  fusion  of  these 
elementary  tone  sensations  into  compound  ones  of  different  qual- 
ities is  comparable,  in  a  general  way,  to  the  fusion  of  simple  color 
sensations,  with  this  exception,  however,  that  in  the  compound 
tone  sensations  we  are  capable  of  distinguishing  more  clearly  the 
fact  that  they  are  composed  of  simpler  elements  ;  the  constituent 
tones  may  be  recognized  by  the  trained  ear  at  least.  The  mechan- 
ism by  which  the  vibrations  of  the  strings  of  the  basilar  mem- 
brane are  conveyed  to  the  hair  cells  and  through  them  to  the  nerve 
fibers  is  a  matter  of  speculation  only,  as  are  also  the  functions  of  the 
remaining  parts  of  the  organ  of  Corti.  It  may  be  suggested, 
perhaps,  that  the  rods  of  Corti  and  Deiters's  cells,  together  with 
the  reticulate  membrane,  with  which  they  are  both  connected, 
form  not  only  a  supporting  apparatus  for  the  hair  cells,  but  also 
a  mechanism  by  which  the  vibrations  of  the  strings  are  commu- 
nicated to  the  hairs  of  the  hair  cells ;  but  the  suggestion  is  unsatis- 
factory, as  the  anatomical  arrangement  does  not  suffice  to  explain 
how  the  vibrations  of  individual  strings  are  transmitted  to  the 
separate  hair  cells.  The  assumption  has  also  been  made  that 
the  tectorial  membrane  acts  as  a  damper  to  the  vibrating  hair  cells 
or  the  reticulate  membrane.  Its  position  as  a  pad  lying  over  the 
rods  of  Corti  and  the  reticulate  membrane  justifies  perhaps  such  an 
assumption.  Many  physiologists,  while  accepting  the  general 
principle  that  the  cochlea  analyzes  the  sound  waves  by  a  mechan- 
ism for  sympathetic  vibrations,  have  been  unwilling  to  admit 
that  the  basilar  membrane  constitutes  such  a  mechanism.  They 
point  to  the  improbability  or  impossibility  of  fibers  of  only  0.36 
mm.  (or  0.5  mm.  at  the  best)  in  length  acting  as  efficient  reso- 
nators, especially  as  they  are  not  entirely  free  and  are  surrounded 
by  liquid.  Attempts  have  been  made,  therefore,  to  select  other 
structures  in  the  cochlea  as  more  likely  to  be  affected  by  sympa- 
thetic vibrations.  Attention  has  been  directed  mainly  to  the 
tectorial  membrane  or  membrane  of  Corti.  Thus,  Ayers*  believes 
that  this  structure  as  seen  in  the  usual  microscopical  prepara- 
tions, is  simply  an  artefact.  Under  normal  conditions  he  believes 
that  it  is  a  band  of  very  long  and  delicate  hairs  projecting  from  the 
hair  cells  and  lying  free  in  the  endolymph.  According  to  his 
view,  it  is  these  hairs  that  take  up  the  vibrations  and  transmit  their 
impulses  directly  to  the  hair  cells.  The  histological  statement  upon 
which  this  view  is  based  has  not,  however,  been  verified.  'More 
recently  v.  Ebner,f  reviving  an  older  view  of  Hasse,  has  suggested 

*  Ayers,  "Journal  of  Morphology,"  6,  1,  1892. 

f  Kolliker,  "Handbuch  d.  Gewebelehre,"  sixth  edition,  vol.  iii,  pt.  n, 
p.  958,  1902;  also  Hardesty,  "American  Journal  of  Anatomy,"  8,  109,  1908. 


EAR    AS    AN    ORGAN    FOR    SOUND    SENSATIONS. 


401 


that  the  tectorial  membrane,  especially  its  free  end,  serves  as  the 
mechanism  for  sympathetic  vibration.  This  membrane  increases 
in  width  from  the  base  to  the  apex  of  the  cochlea  and  varies  in 
thickness  in  its  radial  diameter,  so  that  it  might  be  conceived  to 
respond  to  different  periods  of  vibrations  in  its  different  parts, 
its  movements  being  communicated  directly  to  the  hair  cells  upon 
which  it  rests.  Unfortunately  we  have  no  direct  experimental 
evidence  in  favor  of  any  of  these  views.  Several  observers,  how- 
ever, have  demonstrated  apparently  that,  whatever  may  be  the 
mechanism  for  sympathetic  vibration,  it  is  so  arranged  that  at  the 
base  of  the  cochlea  the  higher  notes  are  received  and  at  the  apex 
the  notes  of  the  lowest  pitch.  Thus,  Munk,  in  experiments  upon 
dogs,  in  which  by  an  operation  through  the  fenestra  rotunda  he  had 
destroyed  the  basal  portion  of  the  cochlea,  found  that  the  animals, 
after  a  temporary  deafness  of  some  days,  could  hear  apparently 
only  low  tones  and  noises.  Baginsky,*  in  a  later  series  of  experi- 
ments, opened  the  bulla  ossea  on  each  side,  destroyed  the  cochlea 
on  one  side  entirely  so  as  to  render  that  ear  deaf,  while  on  the  other 
he  injured  it  in  certain  areas  only.  He  found 
that  when  the  apex  of  the  cochlea  was  des- 
troyed the  animal  appeared  to  perceive  only 
the  high  tones,  c"',  c"",  c'"" '. 

The  fundamental  principle  of  the  theory  of  the 
function  of  the  cochlea  as  developed  by  Helmholtz 
has  been  subjected  to  some  criticism.  The  theory  of  a 
series  of  resonators  each  responding  to  a  definite  note 
does  not  explain  with  entire  satisfaction  some  of  the 
known  acoustic  phenomena.  Thus,  it  is  known  that 
when  two  notes  are  sounded  together  combinational 
tones  may  be  heard,  either  a  low  difference  tone  whose 
pitch  is  equal  to  that  of  the  difference  between  the 
rates  of  the  two  notes,  or  a  summation  tone  whose 
pitch  is  equal  to  the  sum  of  the  vibrations  of  the  two 
notes.  It  is  difficult  to  conceive  that  these  combina- 
tional tones  have  an  objective  existence,  as  vibrations, 
and  the  means  by  which  they  are  perceived  by  the 
cochlea  is  not  explained  satisfactorily  by  the  theory 
of  resonators.  Other  theories  of  the  function  of  the 
cochlea  have  been  proposed  to  avoid  such  difficulties. 
Thus,  Ewald  f  suggests  a  view  according  to  which  the 
basilar  membrane  vibrates  throughout  its  length  for 
each  note.  He  has  shown  that  a  rubber  membrane  of 
the  dimensions  of  the  basilar  membrane  will  be  set 
into  such  vibrations  throughout  its  length  and  when 
examined  under  the  microscope  presents  such  a  pic- 
ture as  is  represented  in  Fig.  178,  in  which  the  crests 
of  the  waves  are  at  a  fixed  interval  for  each  tone.  If 
at  these  intervals  the  corresponding  hair  cells  and 
nerve  fibers  are  supposed  to  be  stimulated,  then  our 
consciousness  would  recognize  each  note  by  its'  appro- 
priate interval.  For  the  application  of  this  theory  to  musical  harmony- 
combinational  tones  and  beats — reference  must  be  made  to  the  original. 

*  Baginsky,  "Virchow's  Archir  f.  pathol.  Anat.,"  94,  65,  1883. 
t  Ewald,  "Archiv  f.  d.  gesammte  Physiologic,"  76,  147,  1899. 
26 


Fig.  178.— To  il- 
lustrate  the  idea  of 
a  fixed  sound  wave. — 
(Ewald.)  The  illus- 
tration shows  a  fun- 
damental note  and  its 
first  overtone. 


402  THE  SPECIAL  SENSES. 

Sensations  of  Harmony  and  Discord. — The  combination  of 
notes  to  produce  various  harmonies  or  intentional  discords  is  a  part 
of  the  theory  of  music,  but  attention  may  be  called  briefly  to  the 
physiological  explanation  offered  by  Helmholtz  to  account  for  the 
fact  that  certain  notes  when  combined  give  us  a  disagreeable  sen- 
sation, appear  rough  and  unpleasant;  while  others,  on  the  contrary, 
produce  pleasant  sensations.  Discord  or  dissonance  is  due,  accord- 
ing to  Helmholtz,  to  the  beats  produced  when  two  dissonant  notes 
are  sounded  together.  On  the  physical  side  the  beat, — that  is,  a 
rhythmical  variation  in  the  intensity  of  the  sound, — is  due  to  the 
phenomenon  of  interference.  If  the  rates  of  vibration  of  two  notes 
are  such  that  at  certain  intervals  the  crests  of  the  waves  fall  to- 
gether and  again  the  crest  of  one  coincides  with  the  hollow  of  the 
other,  the  sound  sensations  will  be  periodically  increased  and 
decreased.  While  there  is  no  fundamental  explanation  for  the 
fact  that  a  regularly  varying  intensity  of  sound  is  disagreeable,  it 
is  a  well-known  phenomenon  and  it  finds  analogies  in  the  other 
sensations, — for  instance,  in  the  very  disagreeable  effect  of  a  flick- 
ering light.  When  two  notes  are  sounded  together  the  number  of 
beats  varies  with  the  difference  between  the  rates  of  vibration; 
thus,  two  notes,  one  of  128  vibrations  and  the  other  of  136  vibra- 
tions, give  8  beats  per  second.  When  the  number  of  beats 
rises  to  33  per  second  the  discord  is  most  disagreeable;  if,  however, 
the  rate  of  interference  is  more  rapid,  the  unpleasant  sensation 
becomes  less  perceptible,  and  beyond  132  per  second  is  not  notice- 
able. When  the  rates  of  vibrations  of  two  tones  are  such  that 
neither  the  fundamentals  nor  any  of  the  overtones  give  beats,  the 
effect  is  that  of  harmony,  the  vibrations  of  one  note  strengthening 
those  of  the  other.  The  most  perfect  harmony  is  that  of  a  note 
sounded  simultaneously  with  another  of  the  same  rate,  ratio  1:1, 
or  with  its  octave,  ratio  1:  2.  The  various  intervals  which  in 
music  have  been  found  to  be  perfectly  consonant  or  which  vary  so 
little  from  it  as  to  be  usable  in  harmonies  are  those  whose  vibra- 
tions bear  a  simple  ratio  to  each  other.  Thus,  the  octave  of  any 
note  has  the  ratio  of  1:2,  the  double  octave  1 :  4,  the  twelfth  1 :  3. 
These  three  intervals  give  absolutely  consonant  sounds.  Other 
intervals — such  as  the  fifth,  2:3,  or  the  major  third,  4:  5 — give 
a  less  perfect  consonance.  Three  or  more  notes  bearing  such  rela- 
tions to  each  other  constitute  a  chord,  the  vibrations  in  the 
major  chord  being,  for  instance,  in  the  ratios  4:5:6, — c'  (128), 
e'  (160),  g'  (192). 

The  Limits  of  Hearing. — The  rates  of  vibration  that  can  be 
perceived  by  the  ear  as  .musical  tones  lie  between  fairly  well- 
defined  limits,  although  in  this  organ,  as  in  the  case  of  the  eye, 
there  are  individual  variations, — variations,  indeed,  which  are 
more  marked  in  the  case  of  the  ear,  since  its  range  of  appreciation 


EAR    AS    AN    ORGAN    FOR    SOUND    SENSATIONS.  403 

is  larger.  The  lowest  rate  of  vibration  that  can  cause  a  musical 
sensation  is  usually  placed  at  24  to  30  per  second,  although  some 
ears  can  still  respond  to  an  octave  lower — about  16  per  second.  To 
most  ears  vibrations  below  16  per  second  are  felt,  if  perceived  at  all, 
as  single  pulses  that  stimulate  the  sensory  nerves  of  the  tympanic 
membrane  itself,  giving  pressure  sensations  rather  than  auditory 
sensations.  It  may  happen,  however,  that  vibrations  too  slow 
to  be  perceived  by  the  ear  as  an  auditory  sensation  will  give 
overtones  of  a  higher  pitch  and  of  sufficient  strength  to  be  recog- 
nized. The  high  limit  of  audibility,  on  the  other  hand,  is  usually 
placed  at  40,000  double  vibrations  per  second,  although  the  various 
estimates  published  vary  so  widely  that  in  this  respect  there  must 
be  great  individual  differences.  The  shrill  notes  of  insects  are 
said  to  be  inaudible  to  some  ears.  Konig,  making  use  of  Kundt's 
method  of  light  powders,  succeeded  in  tuning  a  series  of  forks  to  an 
estimated  rate  of  90,000  double  vibrations  per  second.  It  was 
found  that  those  between  c7  and  c9  (8192  to  32,768)  were  generally 
audible,  while  the  c10  (65,536)  was  inaudible.  The  limit,  therefore, 
lay  between  c9  and  c10.  Notes  near  this  high  limit  are  not,  how- 
ever, usable  in  ordinary  music;  the  sensations  produced  have  a 
disagreeable,  if  not  actually  painful,  shrillness.  The  range  of 
vibrations  employed  in  music  is  illustrated  by  the  seven  octaves 
of  the  piano,  the  notes  varying  from  the  lowest  c  of  32  vibrations 
to  c6  of  4096  vibrations.  The  intervening  series  is  divided  into 
tones  whose  serial  relations  to  each  other  are  expressed  by  the 
ratios  -f  or  V°  and  semitones  of  the  ratio  yf  or  \ f ;  thus,  c"  =  256 
vibrations  and  the  d"  of  the  same  octave  corresponds  to  256  X  f= 
288  vibrations.* 

*  See  Helmholtz,  Popular  Scientific  Lectures,  "Ueber  die  physiologischen 
Ursachen  des  musikalischen  Harmonic,"  Bonn,  1857. 


CHAPTER  XXI. 


IHE  FUNCTIONS  OF  THE  SEMICIRCULAR  CANALS  AND 
THE  VESTIBULE. 

Position  and  Structure. — The  membranous  semicircular  canals 
lie  within  the  bony  semicircular  canals,  the  space  between  being 
filled  with  perilymph  which  communicates  freely  with  that  in  the 
rest  of  the  labyrinth.  Within  the  membranous  canals  is  the  endo- 
lymph,  which  communicates  through  the  five  openings  with  the 
endolymph  in  the  utriculus.  The  canals  lie  in  three  planes  that  are, 
approximately  at  least,  at  right  angles  to  one  another  (Fig.  179). 
The  horizontal  or  external  canals  lie  in  a  horizontal  plane  at  right 

angles  to  the  mesial  or  sagittal 
plane  of  the  body,  and  the  verti- 
cal canals  on  each  side  make  an 
angle  of  about  45  degrees  with 
this  mesial  plane.  The  plane  of 
each  of  the  anterior  canals  is 
parallel  to  that  of  the  posterior  or 
inferior  vertical  canal  of  the  op- 
posite side,  as  represented  in  the 
figure.  At  one  end  of  each  canal, 
near  its  junction  with  the  utricu- 
lus, is  the  swelling  known  as  the 
ampulla,  and  within  the  ampulla 
lies  the  crista  acustica,  containing 
the  hair  cells  with  which  the  nerve 
fibers  communicate,  and  which, 
therefore,  are  considered  as  the 
sense  cells  of  the  organ.  The  hair 
cells  are  cylindrical  and  each 
gives  off  a  long  hair,  consisting 
perhaps  of  a  bundle  of  finer 
hairs,  which  projects  into  the 
interior  of  the  canal  for  a  distance 
of  at  least  28^.  The  nerve  fibers 
distributed  to  these  hair  cells  are  given  off  by  the  vestibular  branch 
of  the  eighth  nerve,  or  more  properly  the  vestibular  nerve,  one 
branch  of  which  (ramus  utriculo-ampullaris)  supplies  the  utriculus 
and  the  ampulla  of  the  superior  and  horizontal  canals,  while  the 
other  (ramus  sacculo-ampullaris)  furnishes  fibers  to  the  sacculus 
and  the  posterior  ampulla. 

404 


Fig.  179.  —  Diagram  to  show  the  posi- 
tion of  the  semicircular  canals  in  the  head 
of  the  bird.  On  each  side  it  will  be  seen 
that  the  three  canals  lie  in  planes  at  right 
angles  to  one  another.  The  external  or 
horizontal  canals  (E)  of  the  two  sides  lie 
in  the  same  plane.  The  anterior  canal  of 


one  side  (A)  lies  in  a  plane  parallel  to  that 
sterior  canal  (P)  of  the  other  side 


of  the 


SEMICIRCULAR    CANALS    AND    THE    VESTIBULE. 


405 


Flourens's   Experiments  upon  the   Semicircular    Canals. — 

Modern  experiments  and  theories  concerning  the  functions  of  the 
semicircular  canal  date  from  the  classical  researches  of  Flourens* 
(1824).  This  investigator  laid  bare  the  canals  in  birds  and  mam- 
mals and  studied  the  effects  of  sections  of  one  or  more  of  them. 
The  experiments  have  since  been  repeated  by  numerous  observers, 


Fig.  180. — Dissection  to  show  the  position  of  the  three  semicircular  canals  in  the  pigeon 
and  the  relations  of  their  ampullary  ends  (from  preparation  made  by  Dr.  Esther  Rosen- 
crantz). 

and  the  results  obtained  have  been  described  in  great  detail,  for  an 
account  of  which  reference  must  be  made  to  original  sources.f  In 
general,  it  may  be  said  that  injuries  to  the  canals  are  followed  by 
certain  more  or  less  definite  movements  of  the  head,  eyes,  and  body, 
and  by  a  disturbance  in  the  power  of  the  animal  to  co-ordinate  nor- 
mally the  muscles  used  in  standing,  locomotion,  or  flying.  The 
character  and  extent  of  these  results  vary  with  the  number  of 
canals  injured,  and,  indeed,  show  a  more  or  less  definite  relationship 

*  Flourens,  "  Recherches  experimentales  sur  les  propriety  et  les  fonctiona 
du  systeme  nerveux,"  second  edition,  1842. 

t  The  literature  of  the  semicircular  canals  and  the  vestibule  is  very  ex- 
tensive. The  complete  bibliography  may  be  obtained  from  the  following 
sources  :  "  Die  Lehren  von  den  Funktionen  der  einzelnen  Theile  des  Ohrlaby- 
rinths,"  by  von  Stein,  1894;  Richet's  "  Dictionnaire  de  Physiologic,"  article 
by  Cyon,  on  "Espace,"  1900.  Ewald,  "Physiolog.  Untersuchungen  u.  d 
Endorgan  des  nervus  octavus,"  1892. 


406  THE    SPECIAL    SENSES. 

to  the  several  canals.  When  the  horizontal  canal  is  cut  on  one  side 
in  pigeons  the  animal  makes  movements  of  the  head  in  the  plane  of 
that  canal,  and  if  the  similar  canal  on  the  other  side  is  also  sec- 
tioned these  movements  are  more  pronounced.  The  animal  may 
also  in  moving  show  an  inability  to  walk  normally  and  a  tendency, 
especially  when  excited,  to  make  abnormal  forced  movements  of 
rotation  of  the  whole  body.  After  such  an  operation  the  pigeon  will 
not  fly  voluntarily  and  if  thrown  into  the  air  is  not  able  to  guide 
its  flight  with  accuracy  and  soon  descends.  Similar  operations 
on  the  anterior  or  the  posterior  canals  cause  movements  of  the  head 
in  the  corresponding  planes  and  a  tendency  in  walking  or  flying 
to  make  forced  movements — somersaults — forward  or  backward. 
When  all  three  canals  are  cut  on  one  or  both  sides  the  animal  shows 
a  distressing  inability  to  maintain  a  normal  position.  The  head  is 
twisted,  it  is  not  able  to  stand  unless  supported,  and  any  attempt 
at  walking  or  flying  results  in  violent  forced  and  inco-ordinated 
movements.  The  animal  makes  continual  somersaults  at  each 
attempt  to  stand  or  walk  and  the  head  is  kept  in  spasmodic,  forceful 
movements,  which  may  produce  injury  or  death.  To  preserve  the 
animal  from  injury  after  such  an  extensive  operation  it  is  necessary 
to  keep  it  wrapped  in  bandages.  It  should  be  added  that  results 
of  this  character  are  obtained  only  when  the  membranous  canals 
are  injured.  If  the  bony  canal  alone  is  cut  and  even  if  the  peri- 
lymph  is  removed  by  suction  no  such  effects  are  obtained.  At 
most  slight  and  relatively  transient  movements  of  the  head  are 
observed.  If  the  exposed  membranous  canal  is  pricked  with  a 
needle  more  violent  movements  result,  and  if  sectioned  these  move- 
ments are  maintained  for  a  longer  period  and  are  accompanied  by 
the  other  results  described.  Similar  effects  have  been  obtained 
from  operations  on  mammals  and  other  animals,  but  the  results 
are  more  pronounced  in  some  animals  than  in  others,  varying 
apparently  with  the  delicacy  of  the  co-ordination  necessary  to  the 
movements  (Ewald).  Thus,  the  movements  of  walking  or  flying 
in  the  pigeon  may  be  assumed  to  require  a  nicer  adjustment  of  the 
muscles  used  than  is  necessary  in  the  swimming  movements  of  the 
fish,  and  in  correspondence  with  this  idea  it  is  found  that  opera- 
tions on  the  canals  of  fishes  are  not  followed  by  conspicuous  effects 
upon  the  movements  of  the  animals. 

Temporary  and  Permanent  Effects  of  the  Operation. — The 
general  effects  of  operations  on  the  semicircular  canals,  so  far  as 
disturbances  of  equilibrium  and  occurrence  of  forced  movements 
are  concerned,  resemble  those  resulting  from  operations  upon  the 
cerebellum,  and,  as  in  the  case  of  the  last  mentioned  organ,  it  is 
found  by  most  observers  that  if  the  animal  is  properly  cared 
for  the  severity  of  the  first  effects  passes  off  to  a  greater  or  less 


SEMICIRCULAL    CANALS    AND    THE    VESTIBULE.  407 

extent.  Flourens  states  that  his  pigeons,  with  two  or  more  canals 
cut,  continued  to  show  the  effects  of  the  operation  almost  with  the 
same  intensity  for  nearly  a  year.  Some  unpublished  experiments 
made  in  the  author's  laboratory  have  given  different  results.* 
Pigeons  with  only  one  canal  cut  recover  practically  completely 
within  ten  or  more  days.  Those  with  two  canals  cut  recover  nearly 
completely  within  a  month,  so  far  as  walking  is  concerned,  although 
they  exhibit  an  unwillingness  to  fly.  Those  with  three  or  more 
canals  cut  never  recover  completely,  but  their  final  condition  is  very 
different  from  that  exhibited  shortly  after  the  operation.  Even 
when  all  six  canals  have  been  cut  the  animal,  if  well  cared  for  in  the 
beginning,  is  able  finally  to  stand  and  walk  and  feed  itself.  It 
is  not  able,  however,  to  fly,  and  in  walking  its  progress  is  uncertain; 
there  is  a  tendency  to  walk  zigzag  or  in  circles,  first  to  one  side,  then 
to  the  other.  If  hurried  or  excited  some  return  of  the  violent 
movements  of  the  head  and  inco-ordination  of  the  movements  of 
locomotion  may  be  seen.  If,  instead  of  cutting  the  canals,  the 
ampullae  are  destroyed,  the  initial  effects  of  the  operation  seem 
to  be  less  violent,  owing  possibly  to  the  fact  that  in  the  former 
case  the  irritative  effects  of  the  lesion  still  have  the  end  organs 
in  the  ampullae  to  act  upon.  Pigeons  with  all  six  ampullae 
destroyed  may  make  eventually  an  excellent  recovery.  Within 
a  few  months  they  walk  and  perch  with  little  difficulty  when 
not  frightened.  In  the  matter  of  flying  they  do  not  recover 
their  former  skill,  but  this  may  be  due  to  lack  of  practice,  since 
in  the  experiments  quoted  (Rosencrantz)  no  provision  was 
made  for  exercise  in  flying.  The  very  marked  degree  of  recovery 
noted,  even  after  loss  of  all  six  ampullae,  seems  to  be  due  to  the 
fact  that  the  animal  learns  to  use  his  other  sensory  data  in 
co-ordinating  his  muscles.  If  after  a  nearly  complete  degree  of 
recovery  has  taken  place  a  new  operation  is  performed  in  which 
the  canals  are  cut,  the  resulting  disturbance  to  motion  is  relatively 
small  and  soon  passes  off.  That  there  is  any  effect  at  all  from 
the  second  operation  may  be  due  to  the  emptying  of  the  endo- 
lymph  and  the  consequent  effect  upon  the  remaining  ampullae, 
or,  if  these  had  all  been  previously  destroyed,  to  the  effect  upon 
the  sense  organs  of  the  vestibular  sacs. 

Direct  Stimulation  of  the  Canals. — The  membranous  canals  or 
their  ampullary  enlargements  have  been  stimulated  by  many 
observers  and  by  many  different  methods — electrical,  chemical, 
and  mechanical.  The  results  of  electrical  stimulation  are  not 
constant  nor  striking,  but  chemical  and  especially  mechanical 
stimulation  in  the  hands  of  many  observers  has  called  forth  definite 
movements  of  head  or  eyes  similar  in  a  general  way  to  those  caused 
by  section  of  the  canal,  but  lasting,  of  course,  for  a  short  time  only. 

*  Experiments  lasting  over  two  years  made  by  Dr.  E.  Rosencrantz. 


408  THE  SPECIAL  SENSES. 

In  experiments  made  upon  dog-fish  Lee*  found  that  when  the 
animal  is  rotated  in  the  planes  of  the  several  canals  there  are  definite 
movements  of  the  eyes  and  fins  for  each  plane  of  rotation.  More- 
over, since  mechanical  stimulation  of  an  ampulla  causes  move- 
ments of  the  eyes  and  fins  identical  with  those  resulting  from 
rotation  of  the  animal  in  the  plane  of  that  canal,  it  follows  as  a 
probable  conclusion  that  the  sense  cells  in  each  ampulla  are 
actually  stimulated  by  movements  in  the  plane  of  its  canal.  In 
man  also  it  may  be  shown  that  the  sensory  endings  in  the  several 
ampullae  are  probably  stimulated  by  rotation  of  the  head  in  the 
corresponding  planes,  and  that  these  stimulations  set  up  definite 
reactions  that  vary  according  to  the  ampulla  most  affected.  Cer- 
tain of  these  reactions  have  been  found  useful  in  otological  prac- 
tice, especially  those  designated  as  the  "Barany  tests."  f  If»  f°r 
example,  a  person  is  rotated  in  a  turning  chair  for  a  number  of 
times  in  one  direction,  say,  to  the  right,  and  then  suddenly  stopped, 
the  following  reactions  may  be  noted  if  the  head  has  been  so  held 
that  the  rotation  is  in  the  plane  of  the  horizontal  canals.  There  is  a 
nystagmus  or  jerking  movement  of  the  eyeballs,  and  a  false  sensa- 
tion, vertigo,  of  movement  to  the  left.  In  addition,  there  is  a 
certain  inaccuracy  in  movements  made  with  the  eyes  closed,  which 
is  brought  out  in  the  "pointing  error"  test  or  "past  pointing."  To 
make  this  test  the  hand  is  stretched  out  so  that  the  finger  points 
to  or  touches  some  object,  e.  g.,  the  finger  of  the  observer. 
With  the  eyes  closed  the  individual  raises  his  extended  arm  to  a 
Vertical  position  and  then  lowers  it  again  to  touch  the  same  point. 
Before  rotation  this  movement  is  accurately  made,  but  after  rota- 
tion he  errs  to  one  side  or  the  other.  If  rotated  horizontally  to  the 
right  he  will  err  or  "past  point"  to  the  right.  The  vertigo,  nystag- 
mus, and  "past  pointing"  will  continue  for  a  number  of  seconds 
(twenty  to  twenty-five)  in  a  normal  person  with  diminishing  in- 
tensity. By  giving  the  head  different  positions  it  is  possible  to 
rotate  it  in  planes  (sagittal,  frontal)  which  involve  the  vertical 
canals,  and  the  character  of  the  responses  obtained  may  be  used 
to  determine  whether  or  not  the  sense-cells  in  these  canals  are 
functioning  normally. 

Effect  of  Section  of  the  Ampullary  or  the  Acoustic  Nerve. — 
Many  of  the  older  and  newer  observers  have  cut  one  or  both  of  the 
acoustic  nerves  or  destroyed  the  entire  labyrinth  on  one  or  both 
sides.  The  effects  described  vary  somewhat  with  the  animals  used, 
but,  in  general,  section  of  the  nerve  on  one  side  is  followed  by 

*  Lee,  "Journal  of  Physiology,"  15,  328,  1903. 

t  Barany,  "British  Medical  Journal,"  1910,  2,  1245;  also  "Transactions  of 
International  Congress  of  Medicine,"  London,  1913;  also  Jones  and  Fisher, 
"Annals  of  Otology,  Rhinology,  and  Laryngology,"  March,  1917. 


SEMICIRCULAR    CANALS    AND    THE    VESTIBULE.  409 

forced  movements,  especially  by  rolling  movements  around  the 
long  axis  of  the  body.  When  the  nerves  are  cut  on  both  sides 
disturbances  in  the  power  to  maintain  equilibrium  perfectly  are 
more  or  less  distinctly  marked.  In  fishes  (dog-fish)  the  animal  may 
swim  or  come  to  rest  in  unusual  positions, — on  the  back  or  side,  for 
instance. 

Is  the  Effect  of  Section  of  the  Canals  Due  to  Stimulation?— 
The  movements  that  result  from  section  of  one  or  more  of  the  canals 
have  been  attributed  by  some  authors  to  stimulations  set  up  by  the 
injury  caused  by  the  operation,  and  by  others  have  been  considered 
as  a  result  of  the  falling  out  of  the  stimuli  normally  and  constantly 
proceeding  from  the  canals.  This  fundamental  question  has  not 
been  decided.  On  the  one  hand,  the  movements  observed  are  simi- 
lar to  those  caused  by  excitation,  which  would  indicate  that  a  stimu- 
lation is  set  up  by  the  operation.  On  the  other  hand,  the  effects  are 
so  long  lasting  as  to  make  it  improbable  that  they  are  entirely  due  to 
the  irritation  of  the  operation.  Moreover,  Gaglio  *  states  that  when 
the  spot  operated  upon  is  cocainized  the  same  effects  follow.  Indeed, 
cocainizing  the  membranous  canals  gives  the  same  results  as  cutting 
them.  It  is  possible,  of  course,  that  both  processes  take  place,  an 
irritative  stimulation  and  a  falling  out  of  normal  impulses,  the 
effects  of  the  latter  being  longer  lasting. 

Theories  of  the  Functions  of  the  Semicircular  Canals. — As 
indicated  briefly  above,  the  facts  regarding  injury  to  and  stimulation 
of  the  semicircular  canals  are  very  numerous  and,  on  the  whole,  fairly 
concordant.  Their  interpretation,  however,  has  offered  great  dif- 
ficulties, and  many  views  have  been  proposed;  almost  every  inves- 
tigator, in  fact,  has,  to  some  extent,  varied  in  his  interpretation  of 
the  precise  functional  significance  of  these  organs. "f  These  views 
may  be  classified,  although  imperfectly,  under  the  following  heads : 

1.  The  old  view,  first  proposed  by  Autenrieth  (1802),  that  the 
canals  or  their  sense  cells  are  stimulated  by  sound  waves  and  give 
us  the  means  of  determining  the  direction  of  sound  in  accordance 
with  their  position  in  three  planes  at  right  angles  to  one  another. 
This  view  has  been  revived  from  time  to  time  by  recent  writers. 

2.  Flourens  himself  believed  that  the  impulses  normally  proceed- 
ing from  these  organs  serve  to  moderate,  or,  as  we  should  say  now, 
to  inhibit  the  movements  of  the  head.     As  soon  as  the  canals  are  cut 
the  movements  that  have  been  kept  under  control  by  their  influence 
are   unrestrained.      On   this   view   the    semicircular    canals    are 
organs  which  reflexly  inhibit  or  restrain  the  voluntary  movements, 
and  thus  take  an  essential  part  in  the  proper  co-ordination  of  such 

*  Gaglio,  "Archives  ital.  de  biologic,"  31,  377,  1899. 

t  For  a  detailed  and  complete  account  of  these  views  to  1892,  see  Stein, 
"Die  Lehren  von  den  Funktionen  der  eizelnen  Theile  des  Ohrlabyrinths  " 
Jena,  1894. 


410  THE  SPECIAL  SENSES. 

movements.     He  did  not  attempt  to  define  the  physiology  of  the 
organs  in  terms  of  the  sensations  aroused. 

3.  The  view  that  the  stimulus  to  the  hair-cells  is  to  be  found  in 
the  varying  pressure  of  the  endolymph.  As  first  proposed  by  Goltz 
(1870),  it  was  assumed  that  the  endolymph  exerts  a  hydrostatic 
pressure  upon  the  hair  cells  which  in  any  given  position  varies  in  the 
different  ampullas  and  varies  with  different  positions  of  the  head. 
The  sensory  impulses  thus  aroused  give  us  a  knowledge  of  the  posi- 
tion of  the  head  and  enable  us,  therefore,  to  control  its  movements 
and  also  those  of  the  body.  On  this  view  these  organs  act  as  sense 
organs  in  maintaining  body  equilibrium  and  may  be  designated  as 
peripheral  sense  organs  of  equilibrium.  Later  observers  (Mach, 
Breuer,  Brown,  et  al.)  modified  this  view  by  the  assumption  that  the 
hair  cells  are  stimulated  not  so  much  by  the  hydrostatic  pressure  of 
the  endolymph  as  by  the  pressure  changes  developed  during  move- 
ments of  the  head,  making  the  organs,  therefore,  a  means  of 
appreciating  especially  the  movements  of  the  head,  a  dynamic 
rather  than  a  hydrostatic  organ  of  equilibrium.  It  was  assumed 
that  rotation  movements  of  the  head  in  the  plane  of  a  canal  set  up 
a  movement  or  pressure  of  the  endolymph  in  the  opposite  direc- 
tion, just  as,  to  use  a  rough  comparison,  when  one  twirls  a  pail  of 
water  in  one  direction  the  water  lags  behind  and  exerts  a  pressure 
in  the  opposite  direction.  According  to  this  hypothesis,  which 
in  some  form  or  other  is  the  view  usually  taught,  the  hair  cells  in 
each  ampulla  are  stimulated  chiefly  by  movements  in  the  plane  of 
that  canal  toward  the  ampulla,  the  pressure  of  the  endolymph  be- 
ing in  the  opposite  direction, — that  is,  from  utriculus  toward  the 
canal.  Moreover,  the  vertical  canals  act  in  pairs  (see  Fig.  179),  the 
superior  or  anterior  vertical  of  one  side  acting  with  the  posterior  or 
inferior  vertical  of  the  other  side,  the  two  canals  lying  in  parallel 
planes.  Movements  in  this  plane  forward  would  stimulate  the 
anterior  ampulla  on  one  side  chiefly,  movements  in  the  same  plane 
backward,  the  posterior  ampulla  of  the  opposite  side.  The  horizon- 
tal canals  also  act  together,  being  stimulated  chiefly  by  rotational 
movements  in  the  horizontal  plane,  the  hair  cells  in  one  responding 
chiefly  to  movements  in  one  direction,  the  other  to  movements  in 
the  same  plane,  but  in  the  opposite  direction.  Rotational 
movements  in  other  planes — sagittal,  oblique,  etc. — would 
affect  two  or  more  of  the  pairs  of  canals  in  proportion  to  the 
degree  that  each  is  involved  in  the  movement  on  the  principle  of 
the  parallelogram  of  forces.*  By  a  mechanism  of  this  sort  it 
may  be  supposed  that  we  are  informed  regarding  the  plane,  di- 
rection, and  extent  of  the  movements  of  the  head  and  are  thereby 
enabled  to  control  these  movements.  The  canals  function  es- 
pecially as  a  dynamic  organ  of  equilibrium,  but  may  also  give  us 
*  Consult  Lee,  loc.  cit. 


SEMICIRCULAR    CANALS    AND    THE    VESTIBULE.  411 

guiding  sensations  when  the  movements  are  progressive  rather  than 
rotational,  and  also  when  the  head  is  at  rest,  although,  as  is  ex- 
plained below,  this  last  function  is  by  some  relegated  to  the  hair 
cells  of  the  utriculus  and  sacculus.  According  to  this  view,  the 
loss  of  the  power  of  maintaining  exact  equilibrium  after  injuries  to 
the  canals  or  section  of  the  nerves  may  be  explained  by  supposing 
that  false  sensations  are  experienced  and  false  compensatory  move- 
ments are  made.  So,  also,  the  vertigo  experienced  after  continued 
rotation  may  be  attributed  to  false  sensations  aroused  by  the 
after-action  of  the  sense  cells,  of  the  ampullae.  Many  deaf-mutes, 
whose  internal  ear  is  supposed  to  be  deficient,  do  not  experience 
vertigo  after  rotation,  and  in  animals  with  the  labyrinth  destroyed 
rotational  movements  fail  to  give  the  sjTnptoms  of  vertigo. 

4.  Ewald,  while  accepting  the  general  view  that  the  sense  cells 
are  stimulated  by  the  pressure  of  the  endolymph,  lays  stress  upon 
the  fact  that  the  nerve  impulses  thus  aroused  have,  as  their  main 
result,  a  reflex  effect  upon  the  tonicity  of  the  voluntary  muscula- 
ture. The  constant  flow  of  impulses  from  these  organs  serves  to 
maintain  the  muscles  in  a  normal  condition  of  tone.  In  animals 
with  the  labyrinth  destroyed  on  both  sides  the  body  musculature 
is  flabby  and  lacking  in  tonicity.  This  view  has  received  consid- 
erable support  from  the  experiments  of  Magnus  and  Klijn.* 
These  authors  made  use  of  cats  thrown  into  the  condition  of  exag- 
gerated tonus,-  known  as  decerebrate  rigidity,  which  follows  upon 
removal  of  the  cerebrum  (section  of  the  cerebral  peduncles).  With 
the  animal  in  this  condition  they  showed  that  different  positions 
of  the  head  in  space  caused  definite  changes  in  the  posture  of  the 
extremities,  and  they  demonstrated  that  these  changes  were  due 
to  labyrinthine  reflexes,  since  they  disappeared  upon  destruction 
of  both  labyrinths. 

Summary. — The  sensations,  if  any,  aroused  through  the  semi- 
circular canals,  are  too  indistinct  to  be  recognized  and  named 
by  an  appeal  to  consciousness,  and  it  would  seem  to  be  wiser 
to  designate  them  after  the  analogy  of  the  muscle  sensations 
simply  as  semicircular  canal  or  labyrinthine  sensations.  Our 
perceptions  or  ideas  of  space  and  direction  are  possibly  founded 
in  part  upon  these  reactions  and  in  part  upon  the  muscular, 
visual,  and  tactile  sensations.  Our  reasoning  with  regard  to 
the  semicircular  canal  sensations  would  be  more  satisfactory 
if  it  could  be  shown  that  the  vestibular  nerve,  after  ending  in 
the  pons,  was  continued  forward  by  sensory  paths  to  the  cortex 
of  the  cerebrum.  As  a  matter  of  fact,  such  paths  have  not 
been  demonstrated,  and  if  we  assume  that  conscious  sensations 
are  mediated  only  through  the  cortex  of  the  cerebrum  we  have 
no  anatomical  proof  that  the  semicircular  canals  give  us  any 
*  Magnus  and  Klijn,  "Pfliiger's  Archiv,"  1912,  145,  455. 


412  THE    SPECIAL    SENSES. 

reaction  in  consciousness.  The  vestibular  nerve  fibers  end  in  the 
nucleus  of  Deiters  and  the  nucleus  of  Bechterew,  through  which 
reflex  connections  are  established  with  the  motor  centers  of  the 
spinal  and  possibly  the  cranial  nerves.  There  is  a  connection 
also  with  the  nucleus  fastigii  of  the  cerebellum  and  through 
this  possibly  with  the  cerebellar  cortex,  although  this  latter 
connection  has  not  been  actually  demonstrated.  With  regard 
to  the  influence  of  the  nerve  impulses  from  the  semicircular  canals 
upon  movements,  all  the  facts  known  seem  to  indicate  that  they 
play  an  important  part  in  the  regulation  or  co-ordination  of  the 
movements  of  equilibrium  and  locomotion.  Inasmuch  as  this  gen- 
eral co-ordination  or  control  seems  to  rest  normally  in  the  nervous 
mechanisms  of  the  cerebellum  and  inasmuch  as  the  vestibular 
nerves  probably  make  connections  with  the  cerebellum,  we  may 
assume  that  the  cerebellum  forms  the  brain  center  through  which 
the  semicircular  canal  impulses  exert  their  influence  upon  co-ordin- 
ated muscular  contractions — the  cerebellum  forms  the  nerve  center 
for  the  semicircular  canals,  or  the  semicircular  canals  form  a  periph- 
eral sense  organ  to  the  cerebellum.  Some  such  hypothesis  seems  to 
be  necessary  to  account  for  the  general  similarity  between  the 
effects  of  lesions  of  the  canals  and  of  the  cerebellum.  Whether  the 
impulses  from  the  canals  are  excitatory  or  inhibitory  or  both,  as 
regards  their  effect  upon  muscular  contractions,  is  not  clearly 
apparent  from  the  experimental  evidence  so  far  furnished,  but 
Ewald's  suggestion  that  they  serve  to  maintain  reflexly  the  tonus 
of  the  body  musculature  is  perhaps  the  most  acceptable  view, 
especially  when  it  is  remembered  that  this  tonicity  may  vary 
in  an  adaptive  way  in  different  muscles  according  to  the  strength 
of  the  stimuli  coming  from  one  or  another  of  the  canals.  In 
regard  to  the  means  by  which  these  nerves  are  normally  stim- 
ulated there  is  also  much  room  for  conjecture,  but  provisionally 
at  least  it  seems  permissible  to  adopt  the  view  that  variations 
in  the  pressure  of  the  endolymph  upon  the  hairs  of  the  hair  cells, 
especially  in  movements  of  rotation,  constitute  the  immediate 
cause  of  their  excitation.  Granting  that  changes  in  position  or 
movement  of  the  head  may  cause  such  variations  in  pressure  the 
theory  offers  a  simple  and  satisfactory  explanation  of  the  mode 
of  excitation  and  the  means  by  which  the  excitation  may  vary 
appropriately  under  different  conditions.  While  the  endolymph 
theory  may  be  criticized  easily,  no  other  equally  satisfactory  theory 
has  been  suggested  to  take  its  place. 

Functions  of  the  Utriculus  and  Sacculus. — These  small  sacs 
contain  sensory  hair  cells  similar  in  general  structure  to  those  found 
in  the  cristse  of  the  ampullary  sacs.  Each  collection  of  hair  cells, 
together  with  the  supporting  cells,  is  designated  as  a  macula.  One 
of  these  is  found  in  the  utriculus,  the  macula  utriculi,  and  another 


SEMICIRCULAR    CANALS    AND    THE    VESTIBULE.  413 

in  the  sacculus,  the  macula  sacculi.  Lying  among  the  hairs  of  the 
hair  cell  are  found  masses  of  small  crystals  of  calcium  carbonate, 
the  otoliths  or  otoconia.  In  this  respect  the  structure  of  the 
macula  differs  strikingly  from  that  of  the  crista.  The  position  and 
connections  of  the  utriculus  and  sacculus  lead  at  first  naturally  to 
the  supposition  that  they  are  stimulated  by  the  sound  waves  of  the 
perilymph,  and  are,  therefore,  concerned  in  the  function  of  hearing. 
The  accepted  views  regarding  the  functions  of  the  cochlea  in  hearing 
make  this  organ  sufficient  for  all  auditory  purposes,  and  there  is  no 
specific  part  of  this  process  tfhat  need  be  attributed  to  the  vestibu- 
lar  sacs.  It  was,  indeed,  at  one  time  suggested  that  their  structure 
adapts  them  to  respond  especially  to  short  and  irregular  vibrations, 
but  no  cogent  reasons  or  facts  have  been  advanced  to  support  this 
view.  The  fact  that  the  sacs  are  so  closely  connected  with  the 
semicircular  canals  suggests  rather  that  the  functions  of  these  organs 
are  similar  and  that  like  the  canals,  therefore,  they  influence  the 
contractions  of  the  muscles  and  function  as  organs  of  equilibrium. 
In  recent  years  the  view  that  has  been  most  discussed  is  that  ad- 
vanced by  Breuer, — namely,  that  these  organs  give  us  information 
regarding  the  position  of  the  head  when  at  rest  and  when  mak- 
ing progressive — that  is,  non-rotary — movements,  supplementing, 
therefore,  the  functions  of  the  semicircular  canals  on  the  supposition 
that  these  latter  act  especially  in  movements  of  rotation.  Or,  as  it 
is  sometimes  expressed,  the  sacs  form  a  static  and  the  canals  a  dy- 
namic organ  of  equilibrium.  According  to  this  view,  the  otoliths 
act  as  a  means  of  mechanical  stimulation  of  the  hairs.  Being 
heavier  than  the  endolymph,  they  press  upon  the  hairs  with  a  force 
varying  with  the  position  of  the  head  and  thus  give  rise  to  sensations 
or  reflexes  which  are  adapted  to  the  maintenance  of  equilibrium. 
Since  the  planes  of  the  two  sacs  are  different,  they  may  be  differ- 
ently affected  by  the  same  position  or  movement.  So  also  in  pro- 
gressive movements  forward  the  weight  of  the  otoliths  may  be  im- 
agined to  exercise  a  stress  of  some  sort  upon  the  hairs.  This  theory 
has  been  the  subject  of  much  investigation,  numerous  experiments 
having  been  made  chiefly  upon  fishes  and  invertebrates.*  Accord- 
ing to  some  observers  destruction  of  these  sacs  or  section  of  their 
nerves  is  accompanied  by  a  distinct  interference  with  the  fish's  nor- 
mal equilibrium:  the  animal  swims  at  times  upon  its  back  or  side 
and  apparently  loses  its  normal  means  of  judging  correctly  its  posi- 
tion. In  many  invertebrates  there  is  present  a  sac,  known  as  the 
otocyst,  containing  hair  cells  and  otoliths.  Its  structure  resembles 
that  of  the  vestibular  sacs  of  the  mammalian  ear,  and  it  has  been 
assumed  that  it  has  a  similar  function.  Experiments  by  numerous 

*  Consult  the  following  papers:  Sewall,  " Journal  of  Physiology,"  4,  339, 
1884;  Lee,  ibid.,  15,  311,  1893,  and  "American  Journal  of  Physiology,"  1, 
128,  1898;  Lyon,  " American  Journal  of  Psychology,"  3,  86,  1900. 


414  THE    SPECIAL    SENSES. 

observers  have  indicated  that  when  the  otoliths  are  removed  the 
animal  shows  disturbances  in  equilibrium,  particularly  in  the  matter 
of  the  compensatory  movements  exhibited  during  rotation.  Others, 
however,  deny  these  facts  and  state  that  invertebrates  without  oto- 
cysts  make  compensatory  movements  when  rotated  and  that  in 
those  with  otocysts  compensatory  movements  and  maintenance  of 
normal  equilibrium  persist  after  destruction  of  the  sacs.  A  very 
ingenious  experiment  reported  by  Kreidl  seems  to  show  that  the  oto- 
liths may  affect  the  hairs  by  their  weight.  When  the  palsemon,  a 
crustacean,  molts  it  casts  off  the  inner  lining  of  the  otocyst,  together 
with  the  otoliths.  The  otocysts  in  these  animals  lie  at  the  base  of 
the  antennules  and  open  freely  to  the  exterior.  After  molting  the 
animal  by  means  of  its  claws  places  fine  grains  of  sand  in  the  otocyst 
to  act  as  otoliths.  Taking  advantage  of  this  peculiarity,  Kreidl 
placed  the  animal,  after  molting,  upon  finely  powdered  iron,  with 
the  result  that  some  of  the  iron  granules  were  deposited  in  the  oto- 
cyst in  place  of  the  usual  grains  of  sand.  When  now  a  magnet  was 
brought  near  to  the  animal  reactions  were  obtained  which  showed 
that  the  pressure  of  the  iron  upon  the  hairs  influenced  its  position. 
The  position  taken  by  the  animal  under  these  conditions  was  such 
as  would  be  expected  as  a  resultant  of  the  forces  of  magnetism  and 
gravity,  and  the  experiment,  therefore,  justifies  the  hypothesis  that 
under  normal  conditions  gravity  affects  the  otoliths  and  through 
them  the  muscular  co-ordination  of  the  animal.  These  experiments 
have  been  confirmed  by  Prentiss.*  This  author  has  shown, 
moreover,  that  if  larval  lobsters  (4th  stage)  are  prevented  from 
obtaining  otoliths  after  moulting  by  placing  them  in  filtered  sea- 
water,  their  movements,  like  those  of  larvse  deprived  of  their 
otocysts,  show  a  distinct  instability  and  lack  of  normal  orientation. 
Some  interesting  results  reported  by  Streeter,*  from  experiments 
made  upon  tadpoles,  demonstrate  in  a  striking  way  the  impor- 
tance of  the  labyrinth  to  the  power  or  property  of  equilibration. 
Up  to  the  sixth  day  after  fertilization  the  tadpole  shows  no  evi- 
dence of  a  power  of  equilibrium,  and  is  not  capable  of  swimming 
freely  in  the  water.  When  the  auditory  vesicles  appear,  after  the 
sixth  day,  the  animal  exhibits  evidence  of  a  sense  of  equilibrium 
and  swims  freely  in  the  water  out  of  contact  with  solid  substances. 
If  at  or  before  the  beginning  of  this  stage  one  of  the  auditory 
vesicles  is  removed,  the  tadpole  shows  evident,  although  tem- 
porary, signs  of  a  defective  power  of  equilibration.  If  both 
vesicles  are  removed  the  animal  seems  to  lose  permanently  its 
power  of  swimming,  and  when  at  rest  lies  in  any  position,  as  though 
it  were  lacking  in  a  sense  of  equilibrium. 

*  Prentiss,  "  Bulletin  of  Museum  of  Comparative  Zoology,"    Harvard, 
1901,  xxxvi,  No.  7. 

t  Streeter,  "  Journal  of  Exp.  Zoology,"  3,  543,  1906;  also  vols.  4  and  16. 


SECTION  IV. 
BLOOD  AND  LYMPH. 


CHAPTER  XXII. 

GENERAL  PROPERTIES:   PHYSIOLOGY  OF  THE 
CORPUSCLES. 

The  blood  of  the  body  is  contained  in  a  practically  closed  system 
of  tubes,  the  blood-vessels,  within  which  it  is  kept  circulating  by  the 
force  of  the  heart  beat.  It  is  usually  spoken  of  as  the  nutritive 
liquid  of  the  body,  but  its  functions  may  be  stated  more  explicitly,  al- 
though still  in  quite  general  terms,  by  saying  that  it  carries  to  the  tis- 
sues foodstuffs  after  they  have  been  properly  prepared  by  the  diges- 
tive organs ;  that  it  transports  to  the  tissues  oxygen  absorbed  from 
the  air  in  the  lungs;  that  it  carries  off  from  the  tissues  various  waste 
products  formed  in  the  processes  of  disassimilation ;  that  it  is  the 
medium  for  the  transmission  of  the  internal  secretion  of  certain 
glands;  and  that  it  aids  in  equalizing  the  temperature  and  water 
contents  of  the  body.  It  is  quite  obvious,  from  these  statements, 
that  a  complete  consideration  of  the  physiological  relations  of  the 
blood  would  involve  substantially  a  treatment  of  the  whole  subject 
of  physiology.  It  is  proposed,  therefore,  in  this  section  to  treat  the 
blood  in  a  restricted  way, — to  consider  it,  in  fact,  as  a  tissue  in  itself, 
and  to  study  its  composition  and  properties  without  special  reference 
to  its  nutritive  relationship  to  other  parts  of  the  body. 

Histological  Structure. — The  blood  is  composed  of  a  liquid  part, 
the  plasma,  in  which  float  a  vast  number  of  microscopical  bodies,  the 
blood  corpuscles.  There  are  at  least  three  different  kinds  of  cor- 
puscles, known  respectively  as  the  red  corpuscles  or  erythrocytes; 
the  white  corpuscles  or  leucocytes,  of  which  in  turn  there  are  a  num- 
ber of  different  kinds;  and  the  blood  plates.  Blood-plasma,  when  ob- 
tained free  from  corpuscles,  is  perfectly  colorless  in  thin  layers — for 
example,  in  microscopical  preparations;  when  seen  in  large  quanti- 
ties it  has  in  man  a  yellow  or  greenish  color,  although  in  some  other 
animals  (dog,  cat)  it  is  as  clear  as  water.  The  red  color  of  blood  is 
not  due,  therefore,  to  coloration  of  the  blood-plasma,  but  is  caused 
by  the  mass  of  red  corpuscles  held  in  suspension  in  this  liquid. 
The  proportion  by  bulk  of  plasma  to  corpuscles  is  usually  given, 
roughly,  as  two  to  one. 

415 


416  BLOOD    AND    LYMPH. 

Blood-serum  and  Defibrinated  Blood. — In  connection  with  the 
explanation  of  the  term  "  blood-plasma  "  just  given  it  will  be  con- 
venient to  define  briefly  the  terms  "  blood-serum  "  and  "  defibrin- 
ated  blood."  Blood,  after  it  escapes  from  the  vessels,  usually  clots 
or  coagulates;  the  nature  of  this  process  is  discussed  in  detail  on 
page  453.  The  clot,  as  it  forms,  gradually  shrinks  and  squeezes  out 
a  clear  liquid  to  which  the  name  blood-serum  is  given.  Serum  re- 
sembles the  plasma  of  normal  blood  in  general  appearance,  but  dif- 
fers from  it  in  composition,  as  will  be  explained  later.  At  present 
we  may  say,  by  way  of  a  preliminary  definition,  that  blood-serum  is 
the  liquid  part  of  blood  after  coagulation  has  taken  place,  as  blood- 
plasma  is  the  liquid  part  of  blood  before  coagulation  has  taken  place. 
If  shed  blood  is  whipped  vigorously  with  a  rod  or  some  similar  object 
while  it  is  clotting,  the  essential  part  of  the  clot — namely,  the  fibrin 
— forms  differently  from  what  it  does  when  the  blood  is  allowed  to 
coagulate  quietly ;  it  is  deposited  in  shreds  on  the  whipper.  Blood 
that  has  been  treated  in  this  way  is  known  as  defibrinated  blood.  It 
consists  of  blood-serum  plus  the  red  and  white  corpuscles,  and  as  far 
as  appearances  go  it  resembles  exactly  normal  blood;  it  has  lost, 
however,  the  power  of  clotting.  A  more  complete  definition  of  these 
terms  will  be  given  after  the  subject  of  coagulation  has  been  treated. 
<  Reaction  of  the  Blood. — When  the  blood  is  tested  with  litmus 
paper  it  gives  a  distinct  alkaline  reaction,  and  if  titrated  with  a 
weak  acid  a  considerable  amount  of  the  acid  may  be  added  before 
the  reaction,  as  tested  by  litmus,  becomes  neutral.  On  account 
of  these  facts  it  was  formerly  believed  that  the  liquid  of  the  blood, 
the  blood-plasma,  is  markedly  alkaline,  owing  to  the  presence  in 
it  of  sodium  carbonate.  It  is  now  realized  that  this  view  was 
founded  on  a  wrong  interpretation  of  the  significance  of  the  color 
changes  given  by  litmus,  and  on  an  inadequate  conception  of  the 
cause  of  acidity  and  alkalinity. 

A  neutral  solution  is  one  in  which  the  hydrogen  and  hydroxyl  ions  exist  in 
equal  concentrations.  If  the  hydrogen  ions  are  in  excess  the  solution  is  acid. 
If  the  hydroxyl  ions  are  in  excess  the  solution  is  alkaline.  In  neutral  solu- 
tions, such  as  pure  water,  it  is  known  also  that  the  product  of  the  concentration 
of  hydrogen  ions  by  the  concentration  of  hydroxyl  ions  is  a  constant. 

H     X     OH     =     K 

Hence  it  follows  that  if  the  value  of  K  is  known  a  determination  of  the  con- 
centration of  either  the  hydrogen  or  the  hydroxyl  ions  suffices  to  give  the 
value  of  the  other  factor.  The  methods  of  determining  hydrogen  ion  concen- 
tration are  more  exact  and  it  is  customary  in  giving  the  reaction  of  blood  or  of 
any  body  liquid,  whether  acid  or  alkaline,  to  express  it  in  terms  of  the  hydrogen 
ion  concentration.  For  neutral  solutions,  such  as  pure  water,  the  value  of  K 
equals  1  X  10~14.  In  such  a  solution,  therefore,  the  hydrogen  ion  concentra- 
tion would  be  1  X  10~7  normal,  or  0.0000001  gram  per  liter.  The  concentra- 
tion of  the  hydroxyl  ions  would  be  the  same.  If,  in  a  given  liquid,  the  concen- 
tration of  hydrogen  ions  was  found  to  be  1  X  10~8  or  0.00000001  gram,  the 


GENERAL  PROPERTIES:  THE  CORPUSCLES.         417 

concentration  of  the  hydroxyl  ions  would  be  1  X  10~6  —  this  liquid  would  have  an 
alkaline  reaction.  Accepting  the  value  of  1  X  1Q-7  as  expressing  the  concentra- 
tion of  hydrogen  ions  in  a  neutral  aqueous  solution,  it  is  found  that  blood  has  a 
slightly  alkaline  reaction,  since  it  has  a  hydrogen  ion  concentration  less  than 
that  of  a  neutral  solution,  namely,  approximately  0.4  X  10~7.  In  physiological 
literature  the  concentration  in  hydrogen  ions  of  the  body  liquids  is  sometimes 
expressed,  as  above,  in  terms  of  the  actual  concentration  in  grams  per  liter, 
blood  being  0.00000004  gram,  but  sometimes  also,  for  convenience  sake,  in 
terms  of  what  is  known  as  the  hydrogen  exponent  expressed  by  the  symbol  pH. 
By  hydrogen  exponent  is  meant  the  logarithm  of  the  number  expressing  the 
concentration.  Since  these  numbers  are  all  negative,  the  logarithms  are  nega- 
tive. In  order  to  obtain  positive  logarithms,  Sorensen,  who  introduced  the 
term,  defined  the  hydrogen  exponent  as  the  logarithm  of  the  reciprocal  of  the 
number  expressing  the  concentration.  Thus  in  blood  the  concentration  in 
hydrogen  ions  is  0.4  X  10~7;  the  hydrogen  exponent  is  the  logarithm  of 

,  or  the  logarithm  of  25,000,000,  namely,  7.39.     The  same  figures 


may  be  obtained  by  extracting  directly  the  logarithm  of  0.4  X  10~7  or  0.00000004 
if  it  is  remembered  that  in  tables  of  logarithms  the  mantissa  is  always  positive. 
Thus,  as  usually  expressed,  the  logarithm  of  0.00000004  is  8.602,  in  which  the 
mantissa  is  positive.  By  adding  algebraically  —8  and  +0.602  we  obtain  the 
expression  —  7.39.  In  this  nomenclature  the  hydrogen  exponent  of  a  neutral 
solution  is  7.  Figures  lower  than  this  express  acid  reactions  and  higher 
figures  an  alkaline  reaction.  Thus,  pH  of  blood  is  7.39,  the  pH  of  urine  is  6, 
the  pH  of  gastric  juice  is  1.4,  and  so  on. 

In  accordance  with  these  facts,  it  is  evident  that  to  determine 
whether  the  blood  is  neutral,  acid,  or  alkaline  it  is  necessary  to  ascer- 
tain its  concentration  in  hydrogen  ions.  Two  methods  are  em- 
ployed in  making  these  determinations.*  One,  the  electrical 
method,  makes  use  of  platinum  electrodes  covered  with  hydrogen 
gas,  and  measures  the  difference  in  electric  potential  when  one  of 
the  electrodes  is  surrounded  by  blood  and  the  other  by  a  solution 
of  a  known  concentration  in  hydrogen  ions;  the  other  is  the 
method  of  selected  indicators.  A  series  of  indicators  may  be 
selected  which  undergo  a  change  in  color  at  certain  concentrations 
of  hydrogen  ions,  and  under  suitable  precautions  the  color  change 
given  to  these  indicators  by  the  blood  may  be  interpreted  in  terms 
of  the  hydrogen-ion  concentration.  In  the  first  determinations  of 
the  reaction  of  the  blood  made  by  the  electrical  method  slightly 
erroneous  figures  were  obtained,  owing  to  the  fact  that  precautions 
were  not  taken  to  examine  the  blood  under  its  normal  carbon-dioxid 
tension.  In  the  body  the  blood  is  surrounded  by  a  medium  con- 
taining carbon  dioxid  under  a  certain  pressure,  for  venous  blood 
about  5  per  cent,  of  an  atmosphere,  or  40  mm.  The  carbon  dioxid 
gives  the  blood  an  acid  reaction,  hence  if  the  blood  is  taken  out  of 
the  body  and  exposed  to  an  atmosphere  practically  free  from  CO2,  it 
will  tend  to  give  off  some  of  this  gas  and  take  on  a  slightly  more  al- 

*  Consult  Michaelis,  "Die  Wasserstoffionen  Konzentration,"  Berlin, 
1914,  and  McClendon,  "Physical  Chemistry  of  Vital  Phenomena,"  Princeton, 
1917. 

27 


418  BLOOD    AND    LYMPH. 

kaline  reaction.  In  making  the  most  accurate  determinations  of 
the  normal  reaction  of  the  blood  it  is  necessary,  therefore,  to  ex- 
amine it  at.  the  temperature  of  the  body,  and  in  an  atmosphere  con- 
taining as  much  CO2  as  is  present  normally  in  the  tissues  of  the  body. 
The  results  of  the  measurements  of  the  reaction  of  the  blood  made 
with  these  precautions  indicate  that  it  has  a  hydrogen-ion  concen- 
tration, varying  from  0.35  X  10"7  to  0.49  X  10"7,  that  is,  from 
0.000000035  to  0.000000049  gram  per  liter.  It  is  evident,  there- 
fore, that  the  blood  possesses  a  hydrogen-ion  concentration  less  than 
that  of  a  neutral  liquid,  and  is  slightly  alkaline,  the  arterial  blood 
being  a  trifle  more  alkaline  than  the  venous  blood  owing  to  the 
fact  that  the  latter  contains  more  CO2.  Determinations  of  the 
reaction  of  the  blood  under  normal  and  abnormal  conditions  show 
that  its  range  of  variation  in  reaction  is  very  limited.  Yet  we 
know  that  in  the  metabolism  of  the  body  acids  and  bases  are  being 
formed  constantly  and  given  to  the  blood,  and  in  our  foods  also  we 
may  ingest  acids  or  alkalies,  which  are  absorbed  into  the  blood  and 
which,  it  might  be  supposed,  would  change  its  reaction.  Since  the 
reaction  remains  remarkably  constant,  it  is  evident  that  regulatory 
mechanisms  must  be  present  to  provide  for  the  elimination  or 
neutralization  of  an  excess  of  either  acid  or  alkali.  A  general  regu- 
lation of  this  kind  is  provided  in  the  activity  of  the  lungs  and  the 
kidneys.  The  concentration  of  CO2  in  the  body  is  kept  within  cer- 
tain normal  limits  by  the  reflex  regulation  of  the  respiratory 
movements.  When  the  amount  of  CO2  tends  to  rise,  as  in  muscular 
exercise,  for  example,  the  corresponding  increase  in  the  ventilation 
of  the  lungs  provides  a  method  of  eliminating  the  excess.  So  also 
the  kidnej^s  furnish  an  abundant  secretion  by  which  any  excess  of 
acids  or  bases  is  prevented  from  accumulating  in  the  blood.  In 
addition  to  the  regulatory  methods  of  this  kind  it  has  been  shown 
that  the  composition  of  the  blood  itself  is  such  that  considerable 
amounts  of  acids  or  alkalies  may  be  added  to  it  directly  without 
altering  distinctly  its  reaction.  This  peculiarity  is  due  to  the 
presence  in  the  blood  of  salts  of  carbonic  and  phosphoric  acid.  We 
find  in  the  blood  a  mixture  of  monosodium  phosphate  and  di- 
sodium  phosphate,  sodium  bicarbonate  and  carbonic  acid,  and  it  has 
been  shown,  by  Henderson*  especially,  that  such  a  mixture  is 
peculiarly  adapted  to  preserve  its  neutrality  within  relatively 
wide  limits  when  acids  or  alkalies  are  added  to  it.  A  mixture  of 
this  kind  constitutes  what  is  frequently  called  a  buffer  solution. 
Monosodium  phosphate  is  weakly  acid,  the  disodium  phosphate 
is  weakly  alkaline,  but  a  mixture  of  the  two  salts  gives  a  neutral 
solution,  and  addition  of  acid  causes  no  perceptible  change  in  the 

*  Henderson,  "American  Journal  of  Physiology,"  21,  427,   1908;  also 
"Science,"  July  27,  1917. 


GENERAL  PROPERTIES:  THE  CORPUSCLES.         419 

reaction,  since  it  acts  to  change  some  of  the  disodium  phosphate  to 
monosodium  phosphate,  and  thus  simply  alters  the  ratio  between 
the  concentrations  of  the  two  salts  to  an  extent  which  does  not  influ- 
ence the  reaction.  The  concentration  of  bicarbonate  of  sodium 
and  carbonic  acid  in  the  blood  is  especially  important  in  preserving 
the  weak  alkalinity  characteristic  of  the  blood.  Here  again  it 
is  the  ratio  of  the  carbonic  acid  to  the  bicarbonate  of  sodium 
which  controls  the  hyrogen-ion  concentration,  and  experiments 
have  shown  that  this  ratio  may  be  varied  within  considerable  limits 
without  materially  influencing  the  reaction.  If  acid  is  added  some 
of  the  bicarbonate  is  broken  up  and  carbonic  acid  is  liberated;  if 
alkali  is  added  some  of  the  carbonic  acid  is  changed  over  to  bicar- 
bonate. In  the  normal  processes  of  the  body  there  is  a  constant 
output  of  acids  which  would  tend  to  change  the  reaction  of  the 
body  liquids  were  it  not  for  the  protection  afforded,  first,  by  the 
buffer  action  of  the  bicarbonate  and  phosphates  of  the  blood,  and, 
second,  by  the  action  of  the  lungs  in  eliminating  an  excess  of  C02 
and  of  the  kidneys  in  excreting  an  excess  of  acid  salts. 

TT   f*<(~\  1 

The  ratio  of  carbonic  acid  to  sodium  bicarbonate,  AT  tr^A  >  *s  given  as  ^ 


for  arterial  blood.*  This  ratio  is  obtained  in  this  way:  In  the  normal  en- 
vironment. of  the  tissues,  that  is  to  say,  in  an  atmosphere  containing  5.5  per 
cent.  CO2,  the  amount  of  CO2  chemically  bound  as  sodium  bicarbonate  is  found 
to  be  60  volume  per  cent.  Addition  of  excess  of  acid  to  100  c.c.  of  blood  liber- 
ates 60  c.c.  of  CO2.  The  CO2  contained  in  solution  in  the  plasmas  as  H2CO3  is 
estimated  from  the  absorption  coefficient  of  CO2,  namely,  0.54.  Since  the 
blood  is  in  an  atmosphere  of  only  5.5  per  cent.  CO2  the  amount  absorbed  for  a 
unit  volume  will  be  0.54  X  0.055  or  0.03,  that  is,  3  volumes  for  each  100  volumes 

TT  OO  ^  1 

of  blood.     The  ratio  *     t^Jl  is  equal  then  to  ^  or  JT-.     If  acids  are  added  to 
JN  axlv^Us  oU      z(J 

the  blood,  as,  for  example,  in  muscular  exercise,  the  denominatior  will  be  dimin- 
ished and  the  reaction  will  tend  to  become  more  acid,  but  this  change  stimu- 
lates the  respiratory  center  and  causes  an  increased  respiratory  activity. 
which  thereby  diminishes  the  numerator  and  restores  the  ratio  to  its  normal 
value.  In  this  way  the  reaction  of  the  blood  is  kept  very  constant  through 
wide  changes  in  physiological  activity. 

Acidosis.—  The  actual  reaction  of  the  blood,  as  stated  above, 
does  not  vary  much  even  under  markedly  pathological  conditions. 
but  the  amount  of  fixed  acids  added  to  the  blood  as  a  result  of 
the  processes  of  metabolism  may  vary  widely  and  may  be  greatly 
increased  under  certain  pathological  conditions,  diabetes  for  ex- 
ample. While  such  an  increase  in  the  acids  added  to  the  blood 
may  not  change  its  actual  reaction  perceptibly,  owing  to  the  pro- 
tective mechanisms  described,  it  will  tend,  of  course,  to  reduce  the 
amount  of  protective  sodium  bicarbonate,  since  these  acids  will 
combine  with  the  sodium  and  drive  off  the  CO2,  which  is  then  re- 
moved by  the  lungs.  The  result  in  such  cases  is  a  diminution  in 
_*  Van  Slyke  and  Cullen,  "Journal  of  Biological  Chemistry,"  1917,  30,  289. 


420  BLOOD    AND    LYMPH. 

the  amount  of  alkali  in  the  blood  available  for  the  protection  of 
the  reaction,  or  as  it  is  frequently  expressed,  a  diminution  in  the 
alkaline  reserve  of  the  body.  Such  a  condition  is  designated  as 
"acidosis,"  although  the  reaction  of  the  blood  is  still  alkaline. 
Two  relatively  simple  reactions  have  been  suggested  to  test  for  the 
existence  of  "acidosis."  One  is  to  determine  the  capacity  of  the 
blood-plasma  to  absorb  CO2  under  a  given  pressure.  The  normal 
CO2  capacity  is  from  50  to  60  per  cent,  and  a  decided  fall  below  this 
level  indicates  a  diminution  in  alkali  in  the  blood.  The  second  is  to 
ascertain  the  amount  of.  sodium  bicarbonate  given  by  mouth  that 
suffices  to  give  an  alkaline  reaction  to  the  urine.  In  acidosis  more 
carbonate  will  be  required  to  give  this  result.* 

Specific  Gravity. — The  specific  gravity  of  human  blood  in  the 
adult  male  may  vary  from  1.041  to  1.067,  the  average  being  about 
1.055.  The  most  satisfactory  method  of  determining  this  factor  is, 
of  course,  to  compare  the  weight  of  a  known  volume  of  blood  with 
that  of  an  equal  volume  of  water,  but  for  observations  upon  human 
beings  such  small  quantities  of  blood  must  be  used  that  recourse  must 
be  had  usually  to  a  more  indirect  method.  Perhaps  the  simplest  of 
the  methods  suggested  is  that  devised  by  Hammerschlag.  t  In  this 
method  a  mixture  is  made  of  chloroform  (sp.  gr.,  1.526)  and  benzol 
(sp.  gr.,  0.889).  The  mixture  is  made  in  such  proportions  as  to 
have  a  specific  gravity  of  about  1.055.  A  drop  of  blood  from  the 
finger  is  shaken  into  this  mixture;  if  the  drop  sinks  to  the  bottom 
it  is  evident  that  the  specific  gravity  of  the  blood  is  higher  than  that 
of  the  mixture,  and  the  reverse  is  true  if  the  drop  rises.  By  adding 
more  of  the  chloroform  or  of  the  benzol,  as  the  case  may  be,  the 
specific  gravity  of  the  mixture  may  be  quickly  altered  so  as  to  be 
equal  to  that  of  the  drop  of  blood,  which  will  then  float  in  the  liquid 
without  a  distinct  tendency  to  rise  or  fall.  The  specific  gravity  of 
the  mixture,  which  is  also  that  of  the  blood,  is  then  determined  by  a 
suitable  hydrometer.  By  the  use  of  such  methods  it  has  been  found  J 
that  the  specific  gravity  varies  with  age  and  with  sex;  that  it  is 
diminished  after  eating  and  is  increased  after  exercise;  that  it  has  a 
diurnal  variation,  falling  gradually  during  the  day  and  rising  slowly 
during  the  night;  and  that  it  varies  greatly  in  individuals,  so  that 
a  specific  gravity  which  is  normal  for  one  may  be  a  sign  of  disease 
in  another.  The  specific  gravity  of  the  corpuscles  is  slightly  greater 
than  that  of  the  plasma.  For  this  reason  the  corpuscles  in  shed 
blood,  when  its  coagulation  is  prevented  or  retarded,  tend  to  settle 
to  the  bottom  of  the  containing  utensil,  leaving  a  more  or  less  clear 

*  See  L.  Henderson,  "Science,"  July  27,  1917;  Sellards,  "The  Principles  of 
Acidosis,"  1917;  and  Van  Slyke  and  Cullen,  Loc.  cit. 

t  Hammerschlag,  "Zeitschrift  f.  klin.  Med.,"  20,  444,  1892. 
J  See  Jones,  "Journal  of  Physiology,"  12,  299,  1891. 


GENERAL  PROPERTIES:  THE  CORPUSCLES.         421 

layer  of  supernatant  plasma.  Among  themselves,  also ,  the  corpuscles 
differ  slightly  in  specific  gravity,  the  red  corpuscles  being  heaviest. 

Red  Corpuscles. — The  red  corpuscles  in  man  and  in  all  the 
mammalia,  with  the  exception  of  the  camel  and  other  members  of 
the  group  Camelidae,  are  biconcave  circular  discs  or,  according  to 
some  authors,  bell-shaped  corpuscles  without  nuclei;  in  the  Cam- 
elidae  they  have  an  elliptical  form.  Their  average  diameter  in 
man  is  given  as  7.7  //  (1  p.  ==  0.001  mm.);  their  number,  which 
is  usually  reckoned  as  so  many  in  a  cubic  millimeter,  varies  greatly 
under  different  conditions  6f  health  and  disease.  The  average 
number  is  given  as  5,000,000  per  c.mm.  for  males  and  4,500,000  for 
females.  The  red  color  of  the  corpuscles  is  due  to  the  presence  in 
them  of  a  pigment  known  as  "hemoglobin."  Owing  to  the  minute 
size  of  the  corpuscles,  their  color  when  seen  singly  under  the  micro- 
scope is  a  faint  yellowish  red,  but  when  seen  in  mass  they  exhibit 
the  well-known  blood-red  color,  which  varies  from  scarlet  in  arterial 
blood  to  purplish  red  in  venous  blood,  this  variation  in  color  being 
dependent  upon  the  amount  of  oxygen  contained  in  the  blood  in 
combination  with  the  hemoglobin.  Speaking  generally,  the  func- 
tion of  the  red  corpuscles  is  to  carry  oxygen  from  the  lungs  to  the 
tissues.  This  function  is  entirely  dependent  upon  the  presence  of 
hemoglobin,  which  has  the  power  of  combining  easily  with  oxygen 
gas.  The  physiology  of  the  red  corpuscles,  therefore,  is  largely  con- 
tained in  a  description  of  the  properties  of  hemoglobin. 

Condition  of  the  Hemoglobin  in  the  Corpuscle. — The  finer  structure 
of  the  red  corpuscle  is  not  completely  known.  It  is  usually  stated 
that  the  corpuscle  is  composed  of  two  substances,  stroma  and  hem- 
oglobin, together  with  a  certain  amount  of  water  and  salts  and 
also  a  certain  amount  of  lecithin  and  cholesterin.  The  stroma  is  a 
delicate,  extensible,  colorless  substance  that  gives  shape  to  the 
corpuscles;  it  forms  a  meshwork  or  spongy  mass  in  which  the 
hemoglobin  is  deposited.  This  latter  substance  forms  the  chief 
constituent  of  the  corpuscle,  since  it  makes  about  32  per  cent,  of  the 
weight  of  the  normal  corpuscle,  and  when  dry  from  90  to  95  per 
eent.  of  the  total  solid  material.  According  to  another  view  the 
corpuscles  are  vesicles  with  an  external  envelope  or  pellicle  in 
which  lecithin  and  cholesterin  are  found,  while  the  hemoglobin  is 
contained  within.*  Whichever  view  may  be  correct,  great  interest 
attaches  to  the  presence  of  the  lecithin  and  cholesterin,  whether 
these  substances  are  found  in  an  external  membrane  or  in  a  stroma 
permeating  the  corpuscle.  According  to  Pascucci  the  lecithin  and 
cholesterin  constitute  as  much  as  30  per  cent,  of  the  dry  weight  of 

*  For  recent  discussions  upon  the  histological  structure  of  the  corpuscles 
see  Weidenreich,  "Anatom.  Anzeiger,"  1905,  xxvii.,  and  Schilling-Toreau. 
"Folia  Haematologica,"  Pt  I,  1912.  14.  95. 


422  BLOOD    AND    LYMPH. 

the  stroma,  that  is,  of  the  portion  of  the  corpuscle  left  after  re- 
moval of  the  hemoglobin.  Such  a  large  proportion  of  these  two 
substances  is  not  found  elsewhere  in  the  body  except  in  the  myelin 
sheath  of  the  nerve  fibers.  It  is  believed  that  they  play  an  impor- 
tant role  in  maintaining  the  integrity  of  the  corpuscles  and 
particularly  in  giving  to  the  peripheral  layer  or  membrane  sur- 
rounding the  corpuscles  certain  characteristic  properties  of 
permeability.  Under  normal  conditions  this  external  layer 
is  easily  permeable  to  water  and  to  certain  substances  in  solution, 
such  as  urea,  alcohol,  and  ether,  but  it  is  said  to  be  impermeable 
to  the  neutral  salts;  the  concentration  of  sodium  chloride,  for 
example,  is  much  greater  in  the  plasma  than  in  the  red  corpuscles. 
The  condition  in  which  the  hemoglobin  exists  within  the  cor- 
puscle is  not  fully  understood.  It  is  evidently  not  in  solution, 
since  the  amount  present  is  too  great  to  be  held  in  solution  in 
the  corpuscle,  and,  moreover,  even  a  thin  layer  of  corpuscles 
is  far  from  being  transparent.  Nor  is  it  deposited  in  the  form 
of  crystals.  It  is  assumed,  therefore,  that  it  is  present  in  an 
amorphous  form.  In  Various  ways,  however,  the  relations  of  the 
hemoglobin  within  the  corpuscle  may  be  disturbed;  so  that  it 
escapes  and  enters  into  solution  in  the  plasma.  Blood  in  which 
this  has  happened  suffers  a  change  in  color,  becoming  a  dark 
crimson,  and  is,  therefore,  known  as  "laked  blood."  Laked  blood 
in  thin  layers  is  quite  transparent  compared  with  the  normal 
blood  with  its  opaque  corpuscles. 

Hemolysis. — The  act  of  discharging  the  hemoglobin  from  the 
corpuscles  so  that  it  becomes  dissolved  in  the  plasma  is  designated 
as  hemolysis,  and  substances  that  cause  this  action  are  spoken  of 
as  hemolytic  agents.  A  number  of  such  agents  are  known;  but, 
although  the  results  of  their  action  are  the  same,  so  far  as  the  hemo- 
globin is  concerned,  the  way  in  which  they  bring  about  this  result 
must  vary  greatly.  Some  of  the  known  methods  of  producing 
hemolysis,  or  rendering  the  blood  "laky,"  are  as  follows:  (1) 
By  the  addition  of  water  to  the  blood  or  by  diminishing  in  any  way 
the  concentration  or  osmotic  pressure  of  the  plasma.  (2)  By  add- 
ing ether  or  chloroform.  (3)  By  the  addition  of  soaps  or  of  the 
higher  fatty  acids,  especially  the  unsaturated  acids.  (4)  By 
adding  bile  or  solutions  of  the  bile-salts.  (5)  By  adding  amyl- 
alcohol.  (6)  By  adding  the  serum  from  the  blood  of  certain 
animals.  (7)  By  adding  saponin  or  sapotoxin.  (8)  By  the 
addition  of  an  excess  of  alkali.  (9)  By  various  toxins  found  in 
snake  venom  or  in  the  serum  of  other  animals  or  among  the  prod- 
ucts of  bacterial  activity  (natural  hemolysins),  or  by  similar  or- 
ganic substances  produced  within  the  body  by  the  process  of  im- 
munizing. Some  of  these  hemolytic  agents,  such  as  ether,  bile 


GENERAL  PROPERTIES:  THE  CORPUSCLES.          423 

salts,  and  soaps,  probably  effect  their  action  by  their  power  of 
uniting  with  the  lipoid  elements  (lecithin,  cholesterin)  in  the 
stroma  of  the  corpuscles.  The  framework  of  the  corpuscles  is 
thus  altered  so  that  the  hemoglobin  is  set  free.  The  action  of  the 
hemolysins  and  of  agents  which  lower  the  osmotic  pressure  of  the 
plasma  demands  a  more  detailed  description,  as  processes  of  great 
practical  importance  are  involved  in  these  changes. 

Hemolysis  Caused  by  Lowering  the  Osmotic  Pressure  of  the  Plasma. 
— The  blood  corpuscles  contain  a  certain  amount  of  water  ( 57  to 
64  per  cent.),  an  amount  insufficient  to  discharge  the  hemoglobin. 
We  may  imagine  that  the  osmotic  pressure  within  the  corpuscle  is 
such,  compared  with  the  osmotic  pressure  exerted  by  the  salts  in 
the  plasma,  that  a  water  equilibrium  is  established,  and  that, 
although  water  molecules  diffuse  into  and  out  of  the  corpuscle, 
the  exchange  is  equal  in  the  two  directions.  If,  however,  the 
outside  plasma  is  diluted  by  the  addition  of  water  to  any  consider- 
able extent,  then  the  osmotic  pressure  outside  the  corpuscles  is 
correspondingly  reduced,  while  that  within  the  corpuscles  is 
unchanged.  Consequently  an  increased  amount  of  water  will 
pass  into  the  corpuscles,  sufficient,  in  fact,  to  mpture  the  cor- 
puscles and  thus  discharge  the  hemoglobin.  It  is  evident, 
therefore,  that  in  injecting  liquids  into  the  circulation  or  in 
diluting  blood  outside  the  body  care  must  be  taken  not  to  use 
solutions  whose  osmotic  pressure  is  markedly  less  than  that  of 
blood-plasma,  otherwise  many  of  the  red  corpuscles  may  be 
destroyed.  Solutions  whose  osmotic  pressure  is  the  same  as 
that  of  the  plasma  are  said  to  be  isosmotic  or  isotonic  with  the 
blood,  those  whose  pressure  is  lower  are  designated  as  hypotonic, 
and  those  whose  pressure  is  higher  as  hypertonic.*  The  salt 
that  is  contained  in  the  plasma  in  largest  amounts  is  sodium 
chlorid.  In  mammalian  serum  it  exists  to  an  amount  equal 
to  0.56  per  cent,  and  is  probably  responsible  for  the  greater 
part  (60  per  cent.)  of  the  osmotic  pressure  shown  by  this  liquid. 
In  making  isotonic  solutions  this  salt  is,  therefore,  generally 
employed.  A  solution  containing  nine-tenths  of  1  per  cent,  of 
sodium  chlorid  (NaCl,  0.9  per  cent.)  gives  the  same  osmotic 
pressure  as  plasma  as  determined  by  the  effect  of  each  on  the 
lowering  of  the  freezing-point  (see  Appendix,  Diffusion,  Osmosis, 
and  Osmotic  Pressure).  Such  a  solution  mixed  with  blood 
should  not  and  does  not  alter  the  water  contents  of  the  corpuscles. 
One  may,  in  fact,  use  a  0.7  per  cent,  solution  of  sodium  chlorid 
without  causing  any  noticeable  hemolysis,  and  this  strength  of 
solution  is  frequently  employed  in  infusions  and  experimental 

*  For  a  full  consideration  of  osmotic  pressure  in  its  relations  to  physio- 
logical processes,  see  Hamburger,  "Osmotischer  Druck  und  lonenlehre  " 
Wiesbaden,  1902. 


424 


BLOOD    AND    LYMPH. 


work;  it  constitutes  what  is  known  in  the  laboratories  as  nor- 
mal saline  or  physiological  saline.  If,  however,  one  uses  a 
lower  concentration,  some  of  the  corpuscles  are  hemolyzed, 
and  the  number  of  corpuscles  destroyed  and  the  rapidity  of 
the  hemolysis  increase  rapidly  with  the  lowering  of  the  osmotic 
pressure.*  While  a  0.9  per  cent,  solution  of  sodium  chlorid 
suffices  in  most  cases  for  infusions  and  for  diluting  blood, 
it  does  not  entirely  replace  the  normal  plasma  or  serum,  since 
these  liquids,  in  addition  to  the  sodium  salts,  contain  salts  of 
calcium,  potassium,  magnesium,  etc.,  each  of  which  has  doubtless 
a  certain  specific  importance.  In  diluting  blood  outside  the  body, 
when  the  dilution  is  large,  better  results  are  obtained  by  using  what 
is  known  as  Ringer's  mixture,  which  consists  of  the  physiological 
saline  solution  plus  small  amounts  of  potassium  and  calcium 
chlorid.  One  formula  for  Ringer's  solution  is: 

Sodium  chlorid 0.9     per  cent. 

Calcium  chlorid 0.026    "       " 

Potassium  chlorid 0.03      "       " 

Hemolysis  Caused  by  the  Action  of  Hemolysins. — It  has  long  been 
known  that  the  serum  of  one  animal  may  destroy  the  red  corpuscles 
of  another  animal.  Thus,  rabbits'  blood  corpuscles  added  to  the 
clear  serum  of  a  dog,  cat,  or  man  are  quickly  destroyed,  with  the 
liberation  of  their  hemoglobin.  This  action  was  formerly  described 
under  the  term  "globulicidal  action  of  serum,"  and  was  compared 
to  the  similar  destructive  (bactericidal)  action,  exhibited  by  serum 
toward  some  bacteria.  In  more  recent  literature  the  term  hemol- 
ysis has  replaced  that  of  "  globulicidal  action/'  and  the  hemolytic 
effect  that  a  serum  may  exert  upon  foreign  corpuscles  is  attributed 
to  the  presence  in  it  of  certain  substances  which  in  general  are  classed 
as  hemolysins.  This  hemolytic  action  is  not  due  to  a  simple  differ- 
ence in  osmotic  pressure.  The  serums  of  the  different  mammalia 
have  all  approximately  the  same  osmotic  pressure;  the  differences 
are  too  slight  to  explain  the  effects  observed.  Moreover,  if  the 
serum  used  is  heated  to  55°  C..  its  hemolytic  action  is  destroyed, 
although  no  noticeable  change  occurs  in  the  osmotic  pressure.  In 
addition  to  the  hemolysins  found  normally  in  the  blood  of  different 
animals  it  was  shown  first  by  Bordet  *  that  they  may  be  produced 
artificially.  The  serum  of  guinea  pigs  has  little  or  no  effect  normally 
on  the  red  corpuscles  of  rabbits'  blood.  If,  however,  one  injects 
some  rabbits'  blood  beneath  the  skin  of  a  guinea-pig  and,  if  neces- 

*  According  to  Brachmachari  ("Studies  in  Hemolysis,"  Calcutta,  1913) 
the  red  corpuscles  in  human  blood  begin  to  hemolyze  in  ^  solutions  of  sodium 
chlorid,  and  the  hemolysis  increases  rapidly  between  this  concentration  and  ^ 
solutions.  Some  corpuscles,  however,  retain  hemoglobin  even  when  the  blood 
is  diluted  with  nine  times  its  volume  of  distilled  water. 

t  Bordet,  "Annales  de  1'Inst.  Pasteur,"  1895. 


GENERAL    PROPERTIES:    THE    CORPUSCLES.  425 

sary,  repeats  the  process  it  will  be  found  that  the  blood  of  this 
particular  guinea  pig  has  now  a  strong  hemolytic  action  toward  the 
red  corpuscles  of  rabbits.  This  method  of  producing  specific 
hemolysins  by  means  of  subcutaneous  or  intraperitoneal  injections 
of  foreign  red  corpuscles  is  designated  as  a  process  of  immunizing, 
and  the  serum  of  the  animal  in  which  a  specific  hemolysin  has  been 
thus  produced  is  frequently  called,  for  convenience,  an  immune 
serum.  These  terms  are  employed  on  account  of  the  essential 
similarity  of  the  processes  involved  to  those  underlying  the  devel- 
opment of  immunity  toward 'special  diseases.  When  the  body  is  in- 
vaded by  pathogenic  bacteria  the  toxic  substances  produced  by  these 
organisms  stimulate  the  tissues  to  form  specific  antitoxins  which 
are  capable  of  neutralizing  the  action  of  the  bacterial  toxins.  The 
body  is  thus  rendered  immune  toward  special  bacteria,  and  that  the 
blood  of  the  immunized  animal  actually  contains  a  definite  anti- 
toxin may  be  shown  in  some  cases  by  the  fact  that  when  injected 
into  another  individual  the  latter  also  acquires  the  specific  immun- 
ity. So  in  regard  to  the  hemolysins.  The  presence  of  the  foreign 
red  corpuscles  causes  the  development  of  a  specific  antibody 
capable  of  destroying  the  special  form  of  red  corpuscle  injected. 
The  substance  in  the  red  corpuscles  which  stimulates  the  tissue  to 
form  an  antibody  is  designated  in  general,  according  to  the  nomen- 
clature of  the  day,  as  an  antigen.  Experiments  indicate  that  the 
antigen  in  the  red  corpuscles  is  not  the  hemoglobin,  but  rather  some 
constituent  of  the  stroma.  This  interesting  reaction  may  be 
obtained  with  other  cells  than  the  red  corpuscles  and  bacteria.  By 
injecting  spermatozoa,  an  antibody  may  be  produced  in  the  blood 
which  destroys  this  particular  form  of  cell,  and  the  same  fact  holds 
good  for  epithelial  cells,  etc.  Moreover,  solutions  of  foreign  proteins 
injected  in  the  same  way  give  rise  to  the  formation  of  definite  anti- 
bodies capable  of  coagulating  or  precipitating  the  special  proteins 
used.  In  this  last  case  the  antisubstance  is  designated  as  a 
precipitin  on  account  of  its  precipitating  effect  on  the  solution 
of  protein  (see  Appendix,  p.  1027).  This  wonderful  protective 
adaptation  of  the  body  toward  the  invasion  of  foreign  cells 
or  proteins  is  at  bottom  doubtless  a  chemical  reaction  dependent 
upon  the  properties  of  the  living  cells,  but  the  nature  of  the  proc- 
esses involved  is  not  at  all  understood,  and  the  phenomenon  is, 
therefore,  designated  provisionally  as  a  biological  reaction.  The 
specific  hemolysins  produced  by  immunization  have  been  studied 
by  Bordet,  Ehrlich,  and  others.*  It  has  been  shown  that  they 

*  See  Wassermann,  "Immune  Sera,  Hemolysins,  Cytotoxins,  and  Pre- 
cipitins,"  translated  by  Bolduan,  New  York,  1904.  Ehrlich  "Collected 
Studies  on  Immunity,"  translated  by  Bolduan,  New  York,  1906.  Simon, 
"Infection  and  Immunity,"  Philadelphia,  1912. 


426  BLOOD    AND    LYMPH. 

are  in  reality  composed  of  two  substances  whose  combined  action 
is  necessary  for  the  hemolysis.  There  is,  first,  a  new  and  specific 
substance  that  is  produced  by  the  body  as  a  consequence  of  the 
injection  of  the  foreign  blood  corpuscles.  This  substance  has  been 
given  different  names,  but  is  known  most  frequently  (Ehrlich) 
as  the  immune  body  (or  amboceptor).  It  is  not  destroyed  by  mod- 
erate heating.  The  immune  body  is  enabled  to  act  upon  the 
corpuscles  by  the  co-operation  of  certain  substances  which  are 
normally  present  in  the  serum  and  are  therefore  not  produced  by 
the  process  of  immunization.  These  substances  are  known  usually 
as  complements,  and  it  is  they  that  are  destroyed  by  heating  to 
55°  C.  If  the  immune  serum  of  a  guinea  pig  is  heated  to  55°  C. 
its  hemolytic  action  upon  rabbits'  corpuscles  is  destroyed.  The 
action  may  be  restored,  however,  by  adding  a  little  of  the  rabbit's 
own  serum,  since  in  terms  of  the  above  hypothesis  the  complements 
are  present  in  normal  serum.  That  is  to  say,  an  experiment  of 
the  following  kind  may  be  performed.  Washed  blood  corpuscles 
of  a  rabbit  plus  immune  serum  from  a  guinea  pig  show  hemolysis. 
Washed  blood  corpuscles  of  a  rabbit  plus  immune  serum  which  has 
been  made  inactive  by  heating  show  no  hemolysis.  Addition  of 
normal  rabbits'  serum  to  this  latter  mixture  again  activates  the 
immune  serum  and  causes  hemolysis.  The  rabbits'  serum  in  this 
case  supplies  the  needed  complement. 

These  facts,  it  should  be  stated,  are  interpreted  somewhat  differently 
by  Bordet.*  The  immune  substance  he  designates  as  a  "substance  sensibila- 
trice"  and  the  complement  as  alexin.  The  latter  forms  the  protective  sub- 
tance  of  the  blood,  but  is  unable  to  act  upon  the  foreign  cells  until  these 
latter  have  been  changed  in  some  way,  that  is,  sensitized  by  the  specific 
immune  substance  developed  during  the  process  of  immunizing. 

In  the  case  of  some  of  the  natural  hemolysins  referred  to 
above  it  has  also  been  shown  that  the  solution  of  the  corpuscles 
depends  upon  the  combined  action  of  two  substances.  This 
point  has  been  made  clear  particularly  in  regard  to  the  snake- 
poisons,  such  as  cobra  venom.  In  these  venoms  there  is  present 
a  substance  analogous  to  the  immune  body  or  amboceptor,  but 
in  order  for  it  to  affect  the  red  corpuscles  it  must  be  activated 
by  a  complement  of  some  sort,  present  in  the  plasma  or  the  red 
corpuscle  itself.  Kyesf  has  given  some  interesting  facts  to 
prove  that  lecithin  is  an  effective  complement  for  these  venoms, 
and  that  probably  it  is  this  definite  substance  which  is  furnished 
by  the  blood  in  activating  the  venom  toxin. 

Speaking  in  general  terms,  the  serum  of  any  animal  is  more  or 
less  hemolytic  in  relation  to  the  blood-corpuscles  of  an  animal  of 
another  species;  but  great  differencss  are  shown  in  this  respect. 
The  blood-serum  of  the  horse  shows  but  little  hemolytic  action 

*  Bordet,  "Studies  in  Immunity,"  translated  by  Gay,  New  York,  1909. 
t  Kyes,  "Berl.  klin.  Wochenschrift,"  1902  and "1903. 


GENERAL    PROPERTIES:    THE    CORPUSCLES.  427 

upon  the  reel  corpuscles  of  the  rabbit  when  compared  with  the 
effect  of  the  serum  of  the  dog  or  cat.  Eels'  serum  has  u  re- 
markably strong  hemolytic  action  upon  the  red  corpuscles 
of  most  mammals;  a  very  minute  quantity  of  this  serum  (0.04 
c.c.)  injected  into  the  veins  of  a  rabbit  will  cause  hemolysis 
of  the  corpuscles  and,  as  a  consequence,  the  appear- 
ance of  bloody  urine  (hemoglobinuria).  It  should  be  added 
that  this  curious  toxic  or  lytic  effect  of  foreign  serums  is  not 
confined  to  the  red  corpuscles.  They  contain  cytotoxins  that  affect 
also  other  tissue  elements,  especially  those  of  the  central  nervous 
system,  and  may  therefore  cause  death.  As  little  as  0.04  c.c.  of 
eels'  serum  injected  into  a  small  rabbit  will  cause  the  death  of  the 
animal,  the  fatal  effect  being  due  apparently  to  an  action  on  the 
vasomotor  and  respiratory  centers  in  the  medulla.  The  hemolytic 
and  generally  toxic  effect  of  foreign  sera  has  been  known  for  a  long 
time.  It  was  discovered  practically  in  the  numerous  attempts  made 
in  former  years  to  transfuse  the  blood  of  one  animal  into  the  veins 
of  another.  It  has  been  found  that  this  process  of  transfusion  as  a 
means  of  combatting  severe  hemorrhage  is  dangerous  unless  the 
blood  is  taken  from  an  animal  of  the  same  or  a  nearly  related 
species.  In  human  beings  the  practice  of  transfusing  blood  has 
greatly  increased  in  recent  years.  The  experience  thus  obtained 
has  shown  that  care  must  be  taken  to  secure  a  donor  whose  blood 
falls  in  the  same  group*  as  that  of  the  recipient,  otherwise  serious 
or  even  fatal  hemolysis  may  occur  in  the  recipient  after  trans- 
fusion. 

Nature  and  Amount  of  Hemoglobin. — Hemoglobin  is  a  very 
complex  substance  belonging  to  the  group  of  conjugated  proteins. 
Under  the  influence  of  heat,  acids,  alkalies,  etc.,  it  may  be  broken 
up,  with  the  formation  of  a  simple  protein,  globin,  belonging  to  the 
group  of  histons  (see  appendix)  and  a  pigment,  hematin.  The 
globin  forms,  according  to  different  estimates,  from  86  to  94  per  cent, 
of  the  molecule,  and  the  hematin  about  4  per  cent.  Other  sub- 
stances of  an  undetermined  character  result  from  the  decomposition.! 
When  the  decomposition  takes  place  in  the  absence  of  oxygen,  the 
products  formed  are  globin  and  hemochromogen,  instead  of  globin 
and  hematin.  Hemochromogen  in  the  presence  of  oxygen  quickly 
undergoes  oxidation  to  the  more  stable  hematin.  Hoppe-Seyler 
has  shown  that  hemochromogen  possesses  the  chemical  grouping 
which  gives  to  hemoglobin  its  power  of  combining  readily  with  oxy- 
gen and  its  distinctive  absorption  spectrum.  On  the  basis  of  facts 
such  as  these,  hemoglobin  may  be  defined  as  a  compound  of  a  protein 
body  with  hematin.  It  seems,  then,  that,  although  the  hemochro- 
mogen or  hematin  portion  is  the  essential  constituent,  giving  to  the 

*  Moss,  "Johns  Hopkins  Hospital  Bulletin,"  1910,  21,  p.  63. 

t  Schulz,  "Zeitschrift  f.  physiologischeChemie,"  24;  also  Lauraw.  ibid.,  26. 


428  BLOOD    AND    LYMPH. 

molecule  of  hemoglobin  its  valuable  physiological  properties  as  a 
respiratory  pigment,  yet  in  the  blood  corpuscles  this  substance  is 
incorporated  into  the  much  larger  and  more  unstable  molecule  of 
hemoglobin,  whose  behavior  toward  oxygen  is  different  from  that 
of  the  hematin  itself,  the  difference  lying  mainly  in  the  fact  that 
the  hemoglobin  as  it  exists  in  the  corpuscles  forms  with  oxygen  a 
comparatively  feeble  combination  that  may  be  broken  up  readily 
with  liberation  of  the  gas. 

Hemoglobin  is  widely  distributed  throughout  the  animal  king- 
dom, being  found  in  the  blood  corpuscles  of  mammalia,  birds, 
reptiles,  amphibia,  and  fishes,  and  in  the  blood  or  blood  corpuscles 
of  many  of  the  invertebrates.  The  composition  of  its  molecule  is 
found  to  vary  somewhat  in  different  animals;  so  that,  strictly 
speaking,  there  are  probably  a  number  of  different  forms  of  hemo- 
globin— all,  however,  closely  related  in  chemical  and  physiological 
properties.  Elementary  analysis  of  dogs'  hemoglobin  shows  the 
following  percentage  composition  (Jaquet) :  C,  53.91;  H,  6.62;  N, 
15.98;  S,  0.542;  Fe,  0.333;  0,  22.62.  Its  molecular  formula  is 
given  as  C758H1203N195S3FeO218,  which  would  make  the  molec- 
ular weight  16,669.  Other  estimates  are  given  of  the  molecular 
formula,  but  they  agree  at  least  in  showing  that  the  molecule  is  of 
enormous  size.  The  hematin  that  is  split  off  from  the  hemoglobin 
is  a  pigment  whose  constitution  is  relatively  simple,  as  is  indicated 
by  its  percentage  formula,  C34H34N4FeO5  (Kiister).  It  contains 
all  of  the  iron  of  the  original  hemoglobin  molecule.  Gamgee  has 
called  attention  to  two  facts  which  seem  to  indicate  that  the  globin 
and  hematin  do  not  exist  as  such  in  the  hemoglobin  molecule. 
Thus,  hematin  is  magnetic,  — that  is,  is  attracted  by  a  magnet, — while 
hemoglobin,  on  the  contrary,  is  diamagnetic.  Globin  alone  rotates 
the  plane  of  polarized  light  to  the  left,  levorotatory,  while  hemo- 
globin solutions  are  dextrorotatory.  The  exact  amount  of  hemo- 
globin in  human  blood  varies  naturally  with  the  individual  and  with 
different  conditions  of  life.  According  to  Preyer,*  the  average 
amount  for  the  adult  male  is  14  grams  of  hemoglobin  to  each  100 
grams  of  blood.  It  is  estimated  that  in  the  blood  of  a  man  weighing 
68  kilograms  there  are  contained  about  500  to  700  grams  of  hem- 
oglobin, which  is  distributed  among  some  25,000,000,000,000  of 
corpuscles,  giving  a  total  superficial  area  of  about  3200  square 
meters.  Practically  all  of  this  large  surface  of  hemoglobin  is 
available  for  the  absorption  of  oxygen  from  the  air  in  the  lungs, 
for,  owing  to  the  great  number  and  the  minute  size  of  the  capil- 
laries, the  blood,  in  passing  through  a  capillary  area,  becomes 
subdivided  to  such  an  extent  that  the  red  corpuscles  stream 
through  the  capillaries,  one  may  say,  in  single  file.  In  circu- 
lating through  the  lungs,  therefore,  each  corpuscle  becomes 
*  "Die  Blutkrystalle,"  Jena,  1871. 


GENERAL  PROPERTIES!  THE  CORPUSCLES.         429 

exposed  more  or  less  completely  to  the  action  of  the  air,  and 
the  utilization  of  the  entire  quantity  of  hemoglobin  must  be 
nearly  perfect.  Instruments  known  as  hemometers  or 
hemoglobinometers  have  been  devised  for  clinical  use 
in  determining  the  amount  of  hemoglobin  in  the  blood  of 
patients.  A  number  of  different  forms  of  this  instrument  are  in 
use.  In  all  of  them,  however,  the  determination  is  made  with  a 
drop  or  two  of  blood,  such  as  can  be  obtained  without  difficulty 
by  pricking  the  skin.  The  amount  of  hemoglobin  in  the  withdrawn 
blood  is  determined  usually'by  a  colorimetric  method, — that  is,  its 
color,  which  is  due  to  the  hemoglobin,  is  compared  with  a  series  of 
standard  solutions  containing  known  amounts  of  hemoglobin,  or 
with  a  wedge  of  colored  glass  whose  color  value  in  terms  of  hemo- 
globin has  been  determined  beforehand.  For  details  of  the  structure 
of  the  several  instruments  employed  and  the  precautions  to  be  ob- 
served in  their  use  reference  must  be  made  to  the  laboratory  guides.* 
Compounds  with  Oxygen  and  Other  Gases. — Hemoglobin  has 
the  property  of  uniting  with  oxygen  gas  in  certain  definite  propor- 
tions, forming  a  true  chemical  compound.  This  compound  is  known 
as  oxyhemoglobin ;  it  is  formed  whenever  blood  or  hemoglobin  solu- 
tions are  exposed  to  air  or  are  otherwise  brought  into  contact  with 
oxygen.  According  to  a  determination  by  Hiifner,t  one  gram  of 
hemoglobin  combines  with  1.36  c.c.  of  oxygen.  These  figures 
would  indicate  the  probability  that  each  molecule  of  hemoglobin 
unites  with  a  molecule  of  oxygen,  since  1.36  c.c.  of  oxygen  weighs 
approximately  0.0019  -\-  gram,  and  the  ratio  of  1  gram  of  hemoglobin 
to  0.0019  gram  of  oxygen  is  that  of  the  molecular  weight  of  hemo- 
globin to  the  molecular  weight  of  oxygen,  that  is,  16669:32  :  : 
1:  0.0019.  It  should  be  stated  that  some  observers  t  find  that  the 
maximum  oxygen  capacity  of  the  blood  may  show  individual  varia- 
tions within  narrow  limits,  and  that,  therefore,  what  we  designate  as 
hemoglobin  may  not  be  a  single  chemical  substance,  but  a  mixture 
of  closely  related  compounds.  Oxyhemoglobin  is  not  a  very  firm 
compound.  If  placed  in  an  atmosphere  containing  no  oxygen 
it  is  dissociated,  giving  off  free  oxygen  and  leaving  behind  hemo- 
globin or,  as  it  is  often  called  by  way  of  distinction,  "reduced 
hemoglobin."  This  power  of  combining  with  oxygen  to  form  a 
loose  chemical  compound,  which  in  turn  can  be  dissociated  easily 
when  the  oxygen  pressure  is  lowered,  makes  possible  the  function 
of  hemoglobin  in  the  blood  as  the  carrier  of  oxygen  from  the  lungs 
to  the  tissues.  The  details  of  this  process  are  described  in  the 
section  on  Respiration.  Hemoglobin  forms  with  carbon  monoxid 
gas  (CO)  a  compound,  similar  to  oxyhemoglobin,  which  is  known 

*  See  Simon,  "A  Manual  of  Clinical  Diagnosis,"  Philadelphia. 

t  "Archiv.  f.  Physiologic,"  1894,  p.  130. 

j  See  Bohr,  in  Nagel's  "Handbuch  der  Physiologic,"  vol.  i,  pt.  1.,  1905. 


430  BLOOD    AND    LYMPH. 

as  carbon  monoxid  hemoglobin.  In  this  compound  also  the  union 
takes  place  in  the  proportion  of  one  molecule  of  hemoglobin  to  one 
molecule  of  the  gas.  The  compound  formed  differs,  however, 
from  oxyhemoglobin  in  being  much  more  stable,  and  it  is  for  this 
reason  that  the  breathing  of  carbon  monoxid  gas  is  liable  to  prove 
fatal.  The  CO  unites  with  the  hemoglobin,  forming  a  firm  com- 
pound; the  tissues  of  the  body  are  thereby  prevented  from  obtain- 
ing their  necessary  oxygen,  and  death  results  from  suffocation  or 
asphyxia.  Carbon  monoxid  forms  one  of  the  constituents  of 
coal-gas.  The  well-known  fatal  effect  of  breathing  coal-gas  for 
some  time,  as  in  the  case  of  individuals  sleeping  in  a  room  in  which 
gas  is  escaping,  is  traceable  directly  to  the  carbon  monoxid.  Nitric 
oxid  (NO)  forms  also  with  hemoglobin  a  definite  compound  that 
is  even  more  stable  than  the  CO  hemoglobin;  if,  therefore,  this 
gas  were  brought  into  contact  with  the  blood,  it  would  cause  death 
in  the  same  way  as  the  CO. 

Oxyhemoglobin,  carbon  monoxid  hemoglobin,  and  nitric  oxid 
hemoglobin  are  similar  compounds.  Each  is  formed,  apparently, 
by  a  definite  combination  of  the  gas  with  the  hematin  portion  of  the 
hemoglobin  molecule,  and  a  given  weight  of  hemoglobin  unites 
presumably  with  an  equal  volume  of  each  gas.  In  marked  contrast 
to  these  facts,  Bohr*  has  shown  that  hemoglobin  forms  a  compound 
with  carbon  dioxid  gas,  carbohemoglobin,  in  which  the  quantitative 
relationship  of  the  gas  to  the  hemoglobin  differs  from  that  shown 
by  oxygen.  In  a  mixture  of  O  and  CO2  the  latter  gas  is  absorbed  by 
hemoglobin  solutions  independently  of  the  oxygen,  so  that  a  solu- 
tion of  hemoglobin  nearly  saturated  with  oxygen  will  take  up  CO2 
as  though  it  held  no  oxygen  in  combination.  Bohr  suggests,  there- 
fore, that  the  O  and  the  CO2  must  unite  with  different  portions  of  the 
hemoglobin — the  oxygen  with  the  pigment  portion  and  the  CO2  possi- 
bly with  the  protein  portion.  Although  the  amount  of  CO2  taken  up 
by  the  hemoglobin  is  not  influenced  by  the  amount  of  O  already  in 
combination,  the  reverse  relationship  does  not  hold  in  all  cases.  It  is 
found  that  the  presence  of  the  CO2  loosens,  as  it  were,  the  combina- 
tion between  the  hemoglobin  and  the  oxygen  so  that  the  oxyhemo- 
globin dissociates  more  readily  than  would  otherwise  be  the  case. 
This  is  observed  at  least  when  the  oxygen  is  under  a  low  pressure, 
?uch  as  occurs,  for  instance,  in  the  capillaries  of  the  tissues.  The 
importance  of  this  fact  in  regard  to  the  oxygen  supply  to  the  tissues 
is  referred  to  more  explicitly  in  the  section  on  Respiration. 

Presence  of  Iron  in  the  Molecule. — It  is  probable  that  iron 
is  quite  generally  present  in  the  animal  tissues  in  connection  with 
nuclein  compounds,  but  its  existence  in  hemoglobin  is  noteworthy 
because  it  has  long  been  known,  and  because  the  important  property 
of  combining  with  oxygen  seems  to  be  connected  with  the  presence 

*  "Skandinavisches  Archiv  f.  Physiologic/'  3,  47,  1892,  and  16,  402,  1904. 


GENERAL    PROPERTIES!    THE    CORPUSCLES. 


431 


of  this  element.  According  to  recent  analyses,  the  proportion  of 
iron  in  hemoglobin  is  constant,  lying  between  0.33  and  0.34  per 
cent.*  The  amount  of  hemoglobin  in  blood  may  be  determined, 
therefore,  by  making  a  quantitative  determination  of  the  iron. 
The  amount  of  oxygen  with  which  hemoglobin  will  combine  may 
be  expressed  by  saying  that  one  molecule  of  oxygen  will  be  fixed  for 
each  atom  of  iron  in  the  hemoglobin  molecule  In  the  decomposi- 
tion of  hemoglobin  into  globin  and  hematin,  which  has  been  spoken 
of  above,  the  iron  is  retained  in  the  hematin. 

Crystals. — Hemoglobin  may  be  obtained  readily  in  the  form  o! 
crystals  (Fig.  181).  As  usually  prepared,  these  crystals  are  really 
oxy hemoglobin,  but  it  has 
been  shown  that  reduced 
hemoglobin  also  crystallizes, 
although  with  more  diffi- 
culty. Hemoglobin  from 
the  blood  of  different  ani- 
mals varies  to  a  marked  de- 
gree in  respect  to  the  power 
of  crystallization  and  the 
form  of  the  crystals,  but  in 
the  various  species  of  any 
one  genus  the  crystals  be- 
long to  one  crystallographic 
group.  From  the  blood  of 
the  rat,  dog,  cat,  guinea-pig, 
and  horse  crystals  are  read- 
ily obtained,  while  hemo- 
globin from  the  blood  of 
man  and  of  most  of  the  ver- 
tebrates crystallizes  much 
less  easily.  Methods  for 
preparing  and  purifying 
these  crystals  will  be  found 
in  works  on  physiological 
chemistry.  To  obtain  speci- 
mens quickly  for  examina- 
tion under  the  microscope, 
one  of  the  most  certain 
methods  is  to  take  some  blood  from  one  of  the  animals  whose  hemo- 
globin crystallizes  easily,  place  it  in  a  test-tube,  add  to  it  a  few  drops 
of  ether,  shake  the  tube  thoroughly  until  the  blood  becomes  laky, — 
that  is,  until  the  hemoglobin  is  discharged  into  the  plasma, — and 
then  place  the  tube  on  ice  until  the  crystals  are  deposited.  Small 
portions  of  the  crystalline  sediment  may  then  be  removed  to  a  glass 
*  Butterfield,  "Zeit.  f.  physiol.  Chemie,"  62,  173,  1909. 


Pig.  181.— Crystallized  hemoglobin  (after 
Frey) :  a,  6,  Crystals  from  venous  blood  of  man ; 
c,  from  the  blood  of  a  cat;  d,  from  the  blood  of 
a  guinea  pig;  e,  from  the  blood  of  a.  hamster; 


/,  from  the 


of  a  squirrel. 


432  BLOOD    AND    LYMPH. 

slide  for  examination.  According  to  Reichert,  the  deposition  of  the 
crystals  is  hastened  by  adding  ammonium  oxalate  to  the  blood  in 
quantities  sufficient  to  make  from  1  to  5  per  cent,  of  the  mixture. 
In  man  and  in  most  of  the  mammalia  hemoglobin  is  deposited  in 
the  form  of  rhombic  prisms;  in  the  guinea-pig  it  crystallizes  in 
tetrahedra  (d,  Fig.  181);  in  the  rat  in  the  form  of  elongated  six- 
sided  plates,  and  in  the  squirrel  in  hexagonal  plates.  In  an  elabo- 
rate and  careful  study  of  the  crystallographic  characters  of  hemo- 
globin from  a  large  number  of  animals  Reichert  and  Brown*  have 
shown  that  differences  exist  between  the  crystals  of  various  species 
of  such  a  character  that  they  may  be  used  to  determine  whether  or 
not  animals  belong  to  the  same  genus.  This  difference  in  crystal- 
line form  implies  some  difference  in  molecular  structure,  and  taken 
together  with  other  known  variations  in  property  shown  by  hemo- 
globin from  different  animals  leads  us  to  believe  that  the  huge  mole- 
cule has  a  labile  structure,  and  that  it  may  differ  somewhat  in  its 
molecular  composition  or  atomic  arrangement  without  losing  its 
physiological  property  of  an  oxygen-carrier.  In  this  connection 
it  is  interesting  to  state  that  the  hemoglobin  of  horses'  blood,  which 
crystallizes  ordinarily  in  large  rhombic  prisms,  may  be  made  to  give 
hexagonal  crystals  by  allowing  it  to  undergo  putrefaction,  and  that 
the  form  of  the  crystals  may  then  be  changed  from  hexagons  to 
rhombs  by  varying  the  temperature  of  the  solutions. f  The  crystals 
are  readily  soluble  in  water,  and  by  repeated  crystallization  the 
hemoglobin  may  be  obtained  perfectly  pure.  As  in  the  case  of 
other  soluble  protein-like  bodies,  solutions  of  hemoglobin  are 
precipitated  by  alcohol,  by  mineral  acids,  by  salts  of  the  heavy 
metals,  by  boiling,  etc.  Notwithstanding  the  fact  that  hemoglobin 
crystallizes  so  readily,  it  is  not  easily  dialyzable,  behaving  in  this 
respect  like  non-crystallizable  colloidal  bodies.  The  compounds 
which  hemoglobin  forms  with  carbon  monoxid  (CO)  and  nitric  oxid 
(NO)  are  also  crystallizable,  the  crystals  being  isomorphous  with 
those  of  oxy hemoglobin. 

Absorption  Spectra. — Solutions  of  hemoglobin  and  its  deriv- 
ative compounds,  when  examined  with  a  spectroscope,  give 
distinctive  absorption  bands. 

Light,  when  made  to  pass  through  a  glass  prism,  is  broken  up  into  its 
constituent  rays,  giving  the  play  of  rainbow  colors  known  as  the  spectrum. 
A  spectroscope  is  an  apparatus  for  producing  and  observing  a  spectrum.  A 
simple  form,  which  illustrates  sufficiently  well  the  construction  of  the  appara- 
tus, is  shown  in  Fig.  182,  P  being  the  glass  prism  giving  the  spectrum.  Light 
falls  upon  this  prism  through  the  tube  (A)  to  the  left,  known  as  the  "colli- 
mator  tube."  A  slit  at  the  end  of  this  tube  (»S)  admits  a  narrow  slice  of  light — 
lamplight  or  sunlight — which  then,  by  means  of  a  convex  lens  at  the  other 
end  of  the  tube,  is  made  to  fall  upon  the  prism  (P)  with  its  rays  parallel.  In 

*  Reichert  and  Brown,  "  The  Crystallography  of  Hemoglobins,"  Carnegie 
Institution  of  Washington,  No.  116,  1909. 

t  Uhlik,  "Archiv  f.  d.  gesammte  Physiologic,"  104,  64,  1904. 


GENERAL  PROPERTIES:  THE  CORPUSCLES.         433 

passing  through  the  prism  the  rays  are  dispersed  by  unequal  refraction,  giving 
a  spectrum.  The  spectrum  thus  produced  is  examined  "by  the  observer  with 
the  aid  of  the  telescope  (5).  When  the  telescope  is  properly  focused  for  the 
rays  entering  it  from  the  prism  (P),  a  clear  picture  of  the  spectrum  is  seen. 
The  length  of  the  spectrum  will  depend  upon  the  nature  and  the  number  of 
the  prisms  through  which  the  light  is  made  to  pass.  For  ordinary  purposes  a 
short  spectrum  is  preferable  for  hemoglobin  bands,  and  a  spectroscope  with  one 
prism  is  generally  used.  If  the  source  of  light  is  a  lamp  flame  of  some  kind, 


Fig.  182. — Spectroscope :  P,  The  glass  prism ;  A ,  the  collimator  tube,  showing  the  slit,  /S, 
through  which  the  light  is  admitted;    B,  the  telescope  for  observing  the  spectrum. 

the  spectrum  is  continuous,  the  colors  gradually  merging  one  into  another 
from  red  to  violet.  If  sunlight  is  used,  the  spectrum  will  be  crossed  by  a 
number  of  narrow  dark  lines  known  as  the  "  Fraunhofer  lines."  The  position 
of  these  lines  in  the  solar  spectrum  is  fixed,  and  the  more  distinct  ones  are 
designated  by  letters  of  the  alphabet,  A,  B,  C,  D,  E,  etc.,  as  shown  in  the  charts 
below.  If  while  using  solar  light  or  an  artificial  light  a  solution  of  any  sub- 
stance which  gives  absorption  bands  is  so  placed  in  front  of  the  slit  that  the 
light  is  obliged  to  traverse  it,  the  spectrum  as  observed  through  the  telescope 
will  show  one  or  more  narrow  or  broad  black  bands  that  are  characteristic 
of  the  substance  used  and  constitute  its  absorption  spectrum.  The  positions 
of  these  bands  may  be  designated  by  describing  their  relations  to  the  Fraun- 
hofer lines,  or  more  directly  by  stating  the  wave  lengths  of  the  portions  of 
the  spectrum  between  which  absorption  takes  place.  Some  spectroscopes  are 
provided  with  a  scale  of  wave  lengths  superposed  on  the  spectrum,  and  when 
properly  adjusted  this  scale  enables  one  to  read  off  directly  the  wave  lengths 
of  any  part  of  the  spectrum. 

When  very  dilute  solutions  of  oxyhemoglobin  are  examined  with 
the  spectroscope,  two  absorption  bands  appear,  both  occurring  in 
the  portion  of  the  spectrum  included  between  the  Fraunhofer  lines 
D  and  E.  The  band  nearer  the  red  end  of  the  spectrum  is  known 
as  the  "a-band";  it  is  narrower,  darker,  and  more  clearly  defined 
than  the  other,  the  "£-band"  (Fig.  183).  The  width  and  distinct- 
ness of  the  bands  vary  naturally  with  the  concentration  of  the  solution 
28 


434 


BLOOD    AND    LYMPH. 


used  (see  Fig.  184)  or,  if  the  concentration  remains  the  same, 
with  the  width  of  the  stratum  of  liquid  through  which  the  light 
passes.  With  a  certain  minimal  percentage  of  oxy hemoglobin 
(less  than  0.01  per  cent.)  the  /9-band  is  lost  and  the  a-band  is  very 
faint  in  layers  1  centimeter  thick.  With  stronger  solutions  the 
bands  become  darker  and  wider  and  finally  fuse,  while  some  of  the 
extreme  red  end  and  a  great  deal  of  the  violet  end  of  the  spectrum 
are  also  absorbed.  The  variations  in  the  absorption  spectrum, 
with  differences  in  concentration,  are  clearly  shown  in  the  accom- 
panying illustration  from  Rollett  *  (Fig.  184) ;  the  thickness  of  the 
layer  of  liquid  is  supposed  to  be  one  centimeter.  The  numbers 
on  the  right  indicate  the  percentage  strength  of  the  oxyhemoglobin 
solutions.  It  will  be  noticed  that  the  absorption  which  takes 


656  W  630  620  610  600  S&)  580  570  560  550  5W  5J0I  520 

oJ..Ml.Hl.nl..J..Mljn.lii.iliiJlMrlil.Jiiillmll!iiilillllii!il.tJ»iilillllllllluilll.iillil.l,.,.liiiilii.il..ll.. 


Fig.  183. — Table  of  absorption  spectra  (Ziemke  and  Mailer) :  1,  Absorption  spectrum 
of  oxyhemoglobin,  dilute  solution ;  2,  absorption  spectrum  of  reduced  hemoglobin ;  3,  ab- 
sorption spectrum  of  methemoglobin,  neutral  solution ;  4,  absorption  spectrum  of  met- 
hemoglobin, alkaline  solution  ;  5,  absorption  spectrum  of  hematin,  acid  solution ;  6,  ab- 
sorption spectrum  of  hematin,  alkaline  solution. 


place  as  the  concentration  of  the  solution  increases  affects  the 
red-orange  end  of  the  spectrum  last  of.  all. 

*  Hermann's  "Handbuch  der  Physiologie,"  vol.  iv.,  1880. 


GENERAL  PROPERTIES:  THE  CORPUSCLES. 


435 


Solutions  of  reduced  hemoglobin  examined  with  the  spectroscope 
show  only  one  absorption  band,  known  sometimes  as  the  "f-band." 
This  band  lies  also  in  the  portion  of  the  spectrum  included  between 
the  lines  D  and  E;  its  relations  to  these  lines  and  the  bands  of 
oxyhemoglobin  are  shown  in  Fig.  183.  The  f-band  is  much  more 
diffuse  than  the  oxyhemoglobin  bands,  and  its  limits,  therefore, 
especially  in  weak  solutions,  are  not  well  denned.  The  width  and 
distinctness  of  this  band  vary  also  with  the  concentration  of  the 
solution.  This  variation  is  ^sufficiently  well  shown  in  the  accom- 
panying illustration  (Fig.  185),  which  is  a  companion  figure  to  the 
one  given  for  oxyhemoglobin  (Fig.  184).  It  will  be  noticed  that 
the  last  light  to  be  ab- 
sorbed in  this  case  is 
partly  in  the  red  end 
and  partly  in  the  blue, 
thus  explaining  the  pur- 
plish color  of  hemoglo- 
bin solutions  and  of 
venous  blood.  Oxy- 
hemoglobin soluti  o  n  s 
can  be  converted  to 
hemoglobin  solutions, 
with  a  corresponding 
change  in  the  spectrum 
bands,  by  placing  the 
former  in  a  vacuum  or, 
more  conveniently,  by 
adding  reducing  solu- 
tions. The  solutions 
most  commonly  used 
for  this  purpose  are  am- 
monium sulphid  and 
Stokes' s  reagent.*  If 
a  solution  of  reduced 
hemoglobin  is  shaken 
with  air,  it  quickly 
changes  to  oxyhemo- 
globin and  gives  two 
bands  instead  of  one 
when  examined  by  the 
spectroscope.  Any  given  solution  may  be  changed  in  this  way  from 
oxyhemoglobin  to  hemoglobin,  and  the  reverse,  a  great  number  of 

*  Stokes 's  reagent  is  an  ammoniacal  solution  of  a  ferrous  salt.  It  is  made 
by  dissolving  2  parts  (by  weight)  of  ferrous  sulphate,  adding  3  parts  of  tar- 
taric  acid,  and  then  ammonia  to  distinct  alkaline  reaction.  A  permanent 
precipitate  should  not  be  obtained. 


0, 


•  BC 


Fig.  184. — Diagram  to  show  the  variations  in  the 
absorption  spectrum  of  oxyhemoglobin  with  varying 
concentrations  of  the  solution. — (After  Rollett.)  The 
numbers  to  the  right  give  the  strength  of  the  oxy- 
hemoglobin solution  in  percentages;  the  letters  give 
the  positions  of  the  Fraunhofer  lines.  To  ascertain 
the  amount  of  absorption  for  any  given  concentration 
up  to  1  per  cent.,  draw  a  horizontal  line  across  the 
diagram  at  the  level  corresponding  to  the  concentra- 
tion. Where  this  line  passes  through  the  shaded  part 
of  the  diagram  absorption  takes  place,  and  the  width 
of  the  absorption  bands  is  seen  at  once.  The  diagram 
shows  clearly  that  the  amount  of  absorption  increases 
as  the  solutions  become  more  concentrated,  especially 
the  absorption  of  the  blue  end  of  the  spectrum.  It 
will  be  noticed  that  with  concentrations  between  0.6 
and  0.7  per  cent,  the  two  bands  between  D  and  E  fuse 
into  one. 


436 


BLOOD    AND    LYMPH. 


0.9 


0.7 


0.6 


0.5 


0,4 


0.3 


0,2 


JO.  I 


0. 


times,  thus  demonstrating  the  facility  with  which  hemoglobin  takes 
up  and  surrenders  oxygen. 

Solutions  of  carbon  monoxid  hemoglobin  also  give  a  spec- 
trum with  two  absorption  bands  closely  resembling  in  posi- 
tion arid  appearance  those  of  oxyhemoglobin.  They  are  dis- 
tinguished from  the 
oxyhemoglobin  bands 
by  being  slightly 
nearer  the  blue  end 
of  the  spectrum,  as 
°-8  may  be  demonstrated 
by  observing  the  wave 
lengths  or,  more  con- 
veniently, by  super- 
posing the  two  spectra. 
Moreover,  solutions  of 
carbon  monoxid  hem- 
oglobin are  not  re- 
duced to  hemoglobin 
by .  adding  Stokes's 
liquid,  two  bands  be- 
ing still  seen  after  such 
treatment.  A  solu- 
tion of  carbon  mon- 
oxid hemoglobin  suit- 
able for  spectroscopic 
examination  may  be 
prepared  easily  by 
passing  ordinary  coal- 
gas  through  a  dilute  oxyhemoglobin  solution  for  a  few  minutes 
and  then  filtering. 

Derivative  Compounds  of  Hemoglobin. — There  are  a  number 
of  pigmentary  bodies  which  are  formed  directly  from  hemoglobin 
by  decompositions  or  chemical  reactions  of  various  kinds.  Some 
of  these  derivative  substances  occur  normally  in  the  body.  The 
best  known  are  as  follows  * : 

Methemoglobin. — When  blood  or  a  solution  of  oxyhemoglobin 
is  allowed  to  stand  for  a  long  time  exposed  to  the  air  it  undergoes 
a  change  in  color,  taking  on  a  brownish  tint.  This  change  is  due  to 
the  formation  of  methemoglobin,  and  it  is  said  that  to  some  extent 
the  transition  occurs  very  soon  after  the  blood  is  exposed  to  the  air, 
and  that,  therefore,  determinations  of  the  quantity  of  hemoglobin 
by  the  ordinary  colorimetric  methods  should  be  made  promptly  to 

*  For  more  detailed  information  concerning  the  chemistry  and  literature 
of  these  compounds,  see  Hammarsten,  "Physiological  Chemistry/'  translated 
by  Mandel;  Abderhalden,  "Lehrbuch  d.  physiolog.  Chemie,"  1914. 


aBC 


Fig.  185. — Diagram  to  show  the  variations  in  the  ab- 
sorption spectrum  of  reduced  hemoglobin  with  vary- 
ing concentrations  of  the  solution  (after  Rollett).  The 
numbers  to  the  right  give  the  strength  of  the  hemo- 
globin solution  in  percentages;  the  letters  give  the  posi- 
tions of  the  Fraunhofer  lines.  For  further  directions 
as  to  the  use  of  the  diagram,  see  the  description  of  Fig. 
184. 


GENERAL    PROPERTIES:    THE    CORPUSCLES.  437 

avoid  a  deterioration  in  color  value.  Methemoglobin  may  be 
obtained  rapidly  by  the  action  of  various  reagents  on  the  blood, 
some  of  them  oxidizing  substances,  such  as  permanganate  of  potash 
or  ferricyanid  of  potash,  some  of  them  reducing  substances.  In- 
deed, it  is  known  that  the  change  may  occur  within  the  blood-vessels 
by  the  action  of  such  bodies  as  the  nitrites,  antifebrin,  acetanilid, 
etc.  According  to  most  observers,  methemoglobin  contains  the 
same  amount  of  oxygen  as  hemoglobin;  it  is  combined  differently, 
however,  forming  a  more  stable  compound,  which  can  not  be  dis- 
sociated by  the  action  of  a,,  vacuum.  On  this  account,  therefore, 
methemoglobin  is  not  capable  of  acting  as  a  respiratory  pigment, 
and  to  the  extent  that  it  is  formed  in  the  blood  this  tissue  suffers  a 
loss  of  its  functional  value  as  a  carrier  of  oxygen.  By  the  stronger 
action  of  reducing  solutions — such  as  ammonium  sulphid — the 
oxygen  may  be  removed  from  the  methemoglobin  and  reduced 
hemoglobin  be  obtained.  Methemoglobin  crystallizes  in  needles, 
and  its  solutions  give  an  absorption  spectrum  which  varies  ac- 
cording as  the  solution  is  neutral  or  has  an  alkaline  reaction.  In 
neutral  solutions  the  characteristic  band  is  one  in  the  orange,  as 
indicated  in  Fig.  183.  In  alkaline  solution  the  absorption  spectrum 
has  three  bands,  two  of  which  are  nearly  identical  with  those  of 
oxyhemoglobin. 

Hematin  (CssHaa^FeOs)  is  obtained  when  hemoglobin  is 
decomposed  by  the  action  of  acids  or  alkalies  in  the  presence  of 
oxygen.  It  may  occur  in  the  feces  if  the  diet  contains  hemoglobin 
or  hematin,  or  in  case  of  hemorrhage  in  the  stomach  or  small  intes- 
tine, since  both  the  pancreatic  and  the  gastric  secretion  break  up 
hemoglobin,  with  the  formation  of  hematin.  It  is  an  amorphous 
substance,  of  a  dark-brown  color,  easily  soluble  in  alkalies  or  in 
acid  alcoholic  solutions.  These  solutions  give  a  characteristic 
absorption  spectrum  which  is  represented  in  Fig.  183.  The 
chemical  structure  of  hematin  has  not  been  established  satisfac- 
torily, but  it  is  probable  that  the  molecule  contains  four  pyrrol 

groups : 

CH  =  CH\ 

>NH. 
CH  =  CH/ 

Two  of  the  amino-acid  derivatives  of  proteins,  tryptophan  and 
prolin  (see  p.  801),  contain  this  same  grouping,  and  it  is  possible, 
therefore,  that  these  amino-acids  may  serve  as  material  from  which 
the  body  constructs  its  hematin. 

Hemin  (CaaH&C^^FeCl)  is  a  derivative  of  hematin,  obtained 
by  the  action  of  hydrochloric  acid  or  chlorids,  in  which  an  hy- 
droxyl  group  is  replaced  by  chlorin.  The  compound  is  obtained 
in  the  form  of  crystals,  which  under  the  microscope  appear  usually 
as  small,  rhombic  plates  of  a  dark-brown  color.  These  crystals 


438  BLOOD    AND    LYMPH. 

may  be  obtained  from  small  quantities  of  blood  stains,  etc.,  no 
matter  how  old,  and  they  have  been  relied  upon,  therefore,  as  a 
sure  and  easy  test  for  the  existence  of  blood, — that  is,  hemoglobin. 
The  test  is  one  that  has  been  much  used  in  medicolegal  cases,  and 
may  be  carried  out  as  follows :  A  bit  of  dried  blood  is  powdered  with 
a  few  crystals  of  NaCl.  Some  of  the  powder  is  placed  upon  a  glass 
slide  and  covered  with  a  cover-slip.  By  means  of  a  pipette  a  drop 
or  two  of  glacial  acetic  acid  is  run  under  the' slip,  and  then  by  draw- 
ing the  slide  repeatedly  through  a  flame  the  acid  is  evaporated  to 
dryness,  taking  care  not  to  heat  the  acid  so  high  as  to  cause  it  to 
boil.  After  the  evaporation  of  the  acid  water  is  run  under  the  slip 
and  the  specimen  is  ready  for  examination  with  the  microscope. 

Hemochromogen  is  obtained  when  hemoglobin  is  decomposed 
by  acids  or  alkalies  in  the  absence  of  free  oxygen.  By  oxidation 
it  is  converted  to  hematin.  Hemochromogen  is  crystalline,  and 
gives  a  characteristic  absorption  spectrum. 

Hematoporphyrin  (CssHagN^e)  differs  from  the  preceding  deriv- 
atives of  hemoglobin  in  that  it  contains  no  iron.  It  may  be  ob- 
tained from  hematin  by  the  action  of  strong  acids,  and  is  of  much 
physiological  interest  because  of  its  relationship  to  the  bile  pig- 
ments, which,  like  it,  are  iron-free  derivatives  of  the  hemoglobin. 
In  old  blood-clots  or  extravasations  it  has  long  been  known  that  a 
colored  crystalline  product  may  be  formed.  This  product  was 
designated  as  hematoi'din  by  Virchow  and  later  was  stated,  on  the 
one  hand,  to  be  identical  with  the  bile  pigment,  bilirubin,  and,  on 
the  other  hand,  to  be  isomeric  with  hematoporphyrin.  It  is  also 
of  interest  to  recall  that  the  green  coloring  matter  of  the  plants, 
chlorophyl,  appears  to  contain  pyrrol  groupings,  and  some  of  its 
derivatives  show  close  relationship  to  derivatives  of  the  hematin. 

Histohematins. — This  name  is  a  general  term  that  has  been  given 
to  the  coloring  matter  found  in  the  tissues,  so  far  as  it  has  the 
property  of  taking  up  oxygen.  The  red  coloring  matter  in  some 
muscles  is  an  example  of  such  a  compound  and  has  been  designated 
specifically  as  myohematin.  According  to  most  observers,  myo- 
hematin  is  identical  with  hemoglobin, — that  is,  the  muscle  substance 
contains  some  hemoglobin, — and  we  may  suppose  that  its  presence 
in  the  tissue  furnishes  a  further  means  for  the  transportation  of 
oxygen  to  the  muscle  protoplasm. 

Bile  Pigments  and  Urinary  Pigments. — These  pigments  are 
referred  to  in  the  description  of  the  composition  of  bile  and  urine. 
In  this  connection  the  fact  may  be  emphasized  that  each  of  them  is 
supposed  to  be  derived  from  hemoglobin,  ahd  each  constitutes,  so 
to  speak,  a  form  of  excretion  of  hemoglobin. 

Origin  and  Fate  of  the  Red  Corpuscles. — The  mammalian  red 
corpuscle  is  a  cell  that  has  lost  its  nucleus.  It  is  not  probable,  there- 
fore, that  any  given  corpuscle  lives  for  a  great  while  in  the  circulation. 


GENERAL    PROPERTIES:    THE    CORPUSCLES.  439 

This  is  made  more  certain  by  the  fact  that  hemoglobin  is  the 
mother  substance  from  which  the  bile  pigments  are  made,  and,  as 
these  pigments  are  being  excreted  continually,  it  is  fair  to  suppose 
that  red  corpuscles  are  as  steadily  undergoing  disintegration  in  the 
blood-stream. 

The  number  of  red  corpuscles  destroyed  daily  in  the  body  has  never  been 
determined  with  any  accuracy,  but  it  may  be  quite  large,  as  would  appear 
from  the  following  approximate  calculation  based  upon  our  incomplete 
knowledge  of  the  amount  of  bile-pigment  secreted  daily.  From  observations 
made  upon  cases  of  biliary  fistulas  in  man  it  is  estimated  that  the  daily  flow 
of  bile  amounts  to  about  15  gmS.  per  kilogram  of  body  weight.  If  we  assume 
in  accordance  with  the  figures  given  by  some  authors  that  the  bile  contains 
as  much  as  C.2  per  cent,  of  pigment,  then  1.95  gms.  of  pigment  will  be  secreted 
per  day  (65  X 15  X. 002).  This  pigment  is  formed  from  approximately  the 
same  weight  of  hematin  and  for  its  formation  would  require  the  destruction 
of  48  gms.  of  hemoglobin,  since  hematin  forms  4  per  cent,  of  the  molecule  of 
hemoglobin  (1.95-i-.04  =  48):  Abderhalden  gives  a  much  more  moderate 
estimate  on  the  assumption  that  the  daily  excretion  of  pigment  in  the  bile 
amounts  only  to  0.5  gm.  This  amount  of  pigment  would  be  obtained  from  12.5 
gms.  of  hemoglobin.  In  order  to  furnish  even  as  much  as  12.5  gms.  of  hemo- 
globin, it  is  evident  that  an  enormous  number  of  red  corpuscles,  approximately 
450,000,000,000,  would  have  to  be  destroyed  daily. 

Just  when  and  how  the  corpuscles  go  to  pieces  is  not  definitely 
known.  It  has  been  suggested  that  their  destruction  takes  place 
in  the  spleen  or  lymph-glands  or  in  the  liver.  Certain  large  cells 
(macrophags)  have  been  described  in  the  spleen  which,  at  times, 
contain  red  blood-corpuscles  or  fragments  of  them  in  their  cyto- 
plasm. In  the  bird  and  some  other  animals  Kyes*  has  been  able 
to  demonstrate  that  the  so-called  Kupffer  cells  of  the  liver  actually 
ingest  red  corpuscles,  and  subsequently  digest  them  so  as  to  liber- 
ate the  iron  of  the  hemoglobin  in  a  form  that  can  be  detected  by 
microchemical  reactions.  These  Kupffer  cells  are  modified  or 
specialized  endothelial  cells  of  the  venous  capillaries  of  the  liver, 
and  the  cells  in  the  spleen  which  have  the  same  property  seem  to  be 
of  the  same  type.  Kyes  proposes  for  them  the  name  hemophags. 
The  large  number  of  these  cells  present  in  the  liver,  and  their  action 
in  destroying  the  red  corpuscles  and  liberating  the  iron  falls  in 
with  the  known  function  of  the  liver  in  producing  an  iron-free 
bile-pigment  from  the  hematin.  Whether  or  not  all  red  corpuscles 
meet  their  fate  in  this  way  cannot  be  determined  at  present.  It 
would  seem  probable  that  some  undergo  hemolysis  while  in  the 
blood-stream,  but  the  facts  given  above  are  the  most  definite  in- 
formation obtained  upon  this  interesting  question.  The  con- 
tinual destruction  of  red  corpuscles  implies,  of  course,  a  continual 
formation  of  new  ones.  It  has  been  shown  satisfactorily  that  in 
the  adult  the  organ  "for  the  production  of  red  corpuscles  is  the 
red  marrow  of  bones.  In  this  tissue  hematopoiesis,  as  the  process 
of  formation  of  red  corpuscles  is  termed,  goes  on  continually,  the 
process  being  much  increased  after  hemorrhages  and  in  certain 

*  Kyes,  "International  Monatsschrift  f.  Anat.  u.  Physiol.,"  31,  543,  1914. 


440  BLOOD    AND    LYMPH. 

pathological  conditions.  The  details  of  the  histological  changes 
will  be  found  in  the  text-books  of  histology.  It  is  sufficient  here 
to  state  simply  that  groups  of  nucleated,  colorless  cells,  erythro- 
blasts,  are  found  in  the  red  marrow.  These  cells  multiply  by 
karyokinesis  and  the  daughter-cells  eventually  produce  hemo- 
globin in  their  cytoplasm,  thus  forming  nucleated  red  corpuscles. 
The  nuclei  are  subsequently  lost,  either  by  disintegration  or  by 
extrusion,  and  the  newly  formed  non-nucleated  red  corpuscles 
(erythrocytes)  are  forced  into  the  blood-stream,  owing  to  a  gradual 
change  in  their  position  during  development  caused  by  the  growing 
hematopoietic  tissue.  When  the  process  is  greatly  accelerated,  as 
after  severe  hemorrhages  or  in  certain  pathological  conditions, 
red  corpuscles  still  retaining  their  nuclei  (normoblasts)  may  be 
found  in  the  circulating  blood,  having  been  forced  out  prematurely. 
Such  corpuscles  may  subsequently  lose  their  nuclei  while  in  the 
blood-stream.  In  the  embryo,  hematopoietic  tissue  is  found  in 
parts  of  the  body  other  than  the  marrow,  notably  in  the  liver  and 
spleen,  which  at  that  time  serve  as  organs  for  the  production  of 
new  red  corpuscles.  In  the  blood  of  the  young  embryo  nucleated 
red  corpuscles  are  at  first  abundant,  but  they  become  less  numerous 
as  the  fetus  grows  older.*  It  is  interesting  to  note  that  in  the 
adult  after  severe  anemias — e.  g.,  pernicious  anemia — and  in  rabbits 
after  the  injection  of  saponin  the  spleen  may  again  take  on  its 
hematopoietic  function.  The  venous  sinuses  become  crowded  with 
cells  of  the  marrow  type.f 

Variations  in  the  Number  of  Red  Corpuscles. — The  average 
number  of  red  corpuscles  for  the  adult  male,  as  has  been  stated 
already,  is  usually  given  as  5,000,000  per  c.mm.  The  number 
is  found  to  vary  greatly,  however.  Outside  pathological  con- 
ditions, in  which  the  diminution  in  number  may  be  extreme,  dif- 
ferences have  been  observed  in  human  beings  under  such  conditions 
as  the  following:  The  number  is  less  in  females  (4,500,000) ;  it  varies 
in  individuals  with  the  constitution,  nutrition,  and  manner  of  life; 
it  varies  with  age,  being  greatest  in  the  fetus  and  in  the  new-born 
child;  it  varies  with  the  time  of  the  day,  showing  a  distinct  diminu- 
tion after  meals;  in  the  female  it  varies  somewhat  in  menstruation 
and  in  pregnancy,  being  slightly  increased  in  the  former  and  di- 
minished in  the  latter  condition. 

Variation  with  Altitude. — Perhaps  the  most  interesting  of  the 
conditions  that  may  influence  the  number  of  the  blood  corpuscles 
is  a  change  in  altitude.  Attention  was  first  directed  to  this  point 
by  Bert,J  who  believed  that  the  diminished  supply  of  oxygen  in  high 

*Howell,  "Life  History  of  the  Blood  Corpuscles,"  etc.,  "Journal  of 
Morphology,"  1890,  vol.  iv.;  Bunting,  "Univ.  of  Pennsylvania  Medical 
Bulletin,"  1903,  xvi.,  200. 

t  See  Bunting,  "The  Journal  of  Experimental  Medicine,"  1906,  viii.,  625. 

J  Bert,  "La  pression  baroe"mtrique,"  1878,  p.  1108. 


GENERAL  PROPERTIES!  THE  CORPUSCLES.        441 

altitudes  may  be  compensated  by  an  increased  amount  of  hemo- 
globin, and  subsequently  Viault*  demonstrated  that  living  for  a 
short  time  at  very  high  altitudes  (4000  meters)  causes  a  marked  in- 
crease in  the  number  of  red  corpuscles, — an  increase,  for  instance, 
from  5,000,000  per  c.mm.  to  7,000,000  or  even  8,000,000.  This  fact 
has  since  been  investigated  with  great  care  by  a  large  number  of 
observers  and  under  a  great  variety  of  conditions.  The  observation 
has  been  abundantly  confirmed,  and  indeed  it  would  seem  that  the 
reaction  takes  place  very  quickly.  Within  twenty-four  hours, 
according  to  some  observers;  and  in  less  time,'  according  to  others 
who  have  experimented  during  balloon  ascensions  (Gaule,  Hallion, 
and  Tissot).  the  increase  in  the  number  of  corpuscles  may  be  de- 
tected, although  the  maximum  increase  comes  on  more  gradually. 
According  to  Kemp,  f  the  number  of  blood  plates  is  also  greatly 
increased  by  high  altitudes,  while  the  leucocytes  are  not  affected. 
There  has,  however,  been  much  difference  of  opinion  as  to  whether 
this  increase  in  number  of  the  red  corpuscles  is  relative  or  absolute, 
— that  is,  whether  the  total  number  of  red  corpuscles  in  the  blood, 
and  therefore  probably  the  total  amount  of  hemoglobin,  is  increased, 
or  whether  it  is  simply  an  apparent  increase  due,  for  instance,  to  a 
diminution  in  the  water  of  the  blood  and  a  consequent  concentration 
as  regards  the  number  of  corpuscles,  or  to  a  variation  in  the  distri- 
bution of  the  corpuscles  between  the  vessels  of  the  skin  and  those 
of  the  internal  organs.  The  results  published  upon  these  questions 
have  been  conflicting.  According  to  one  set  of  observers  there  is 
an  absolute  increase  in  the  total  number  of  red  corpuscles,  and 
therefore  in  the  total  amount  of  hemoglobin.  There  seems  to  be 
little  doubt  that  such  a  change  occurs  in  cases  of  long  residence 
in  high  altitudes,  and  we  may  assume  that  the  diminished  amount 
of  oxygen  in  the  air  or  some  other  condition  peculiar  to  these 
altitudes  acts  as  a  stimulus  to  the  blood-forming  tissues  (red  mar- 
row) and  augments  the  output  of  corpuscles  and  hemoglobin. 
The  increase  in  number  of  corpuscles  and  percentage  of  hemo- 
globin occurs  slowly  upon  changing  from  a  low  to  a  high  altitude, 
and  their  inverse  change  upon  returning  to  a  low  altitude  also 
occurs  gradually.  An  illustration  of  the  relationship  between 
altitude  and  amount  of  hemoglobin  is  given  in  Fig.  185&.  Ac- 
cording to  another  set  of  observers,  the  increase  in  the  number 
of  red  corpuscles  is  due  to  a  concentration  of  the  blood.  The 
blood-plasma  is  reduced  in  quantity,  perhaps  by  transuda- 
tion.of  water  into  the  tissues,  and,  therefore,  the  number  of  red 
corpuscles  and  the  amo"unt  of  hemoglobin  become  greater  for  each 
cubic  millimeter.  If  we  assume  that  this  smaller  bulk  of  blood, 
more  concentrated  in  corpuscles  and  hemoglobin,  circulates 

*  Viault,  "Comptes  rendus  de  1' academic  des  sciences,"  1890  and  1891. 
t  Kemp,  "American  Journal  of  Physiology,"  10,  34,  1904. 


442 


BLOOD    AND    LYMPH. 


more  rapidly,  then  also  the  oxygen-carrying  capacity  of  the 
blood  is  increased.  In  favor  of  this  view,  Abderhalden,  for  in- 
stance, has  claimed  that  if  animals  of  the  same  species  and  same 
litter  are  bled  to  death  and  the  total  quantity  of  hemoglobin 
is  estimated,  the  average  figures  obtained  for  the  animals  at  low 
Haemoglobin. 


280 
170 
100 
150 
140 
130 
120 

iro 

100 
90 
80 
70 
60 
SO 

800          "750           700           650          60O          550          BOO          450          40O         35O          3OO 

iliide 

inFt. 

20,000 
25.00O 
24.000 
23iOOO 
22.000 
21,000 
20.00O 

10.000 

18.000 
17.00O 
16.000 
15.000 
14.000 
13.000 
1V5.000 
11,000 
10,000 
9.000 
8,000 
7.000 
6,000 
5,000 
4,000 
3.00O 
2,000 
1.000 
0 

/ 

- 

/ 

/ 

- 

/ 

- 

J_ 

''' 

- 

^ 

^ 

/-"' 

"' 

- 

...•/ 

^ 

^ 

^  , 

y 

•-& 

,'' 

.-°-°" 

^ 

/ 

X 

- 

..-•1 

& 

/ 

'/ 

- 

er 

. 

/•<? 

7 

- 

$ 

T 

/& 

? 

- 

i    / 

/ 

i 

• 

• 

- 

70O    65O    60O    55O    50O    45O    40O 

Almospheric  pressure  in  mm  of  mercury: 


350 


300 


Fig.  185  a. — To  show  the  relationship  between  altitude  and  the  percentage  of  hemoglobin 
in  the  blood.  Figures  along  the  bottom  give  the  atmospheric  pressure ;  along  the  ordinate  to 
the  right  the  altitude  in  feet,  and  along  the  ordinate  to  the  left  the  percentage  of  hemoglobin. — 
(Fitzgerald.} 

levels  are  the  same  as  for  those  at  the  high  altitudes.  Zuntz  has, 
however,  called  attention  to  the  fact  that  when  Abderhalden's 
figures  are  estimated  per  kilogram  of  weight  they  show  an  in- 
crease in  total  hemoglobin  in  the  high  altitudes,  and  he  and  other 
observers  have  obtained  similar  results.  It  seems  certain,  there- 


GENERAL    PROPERTIES:    THE    CORPUSCLES.  443 

fore,  that  high  altitudes  cause  eventually  a  marked  increase  in 
the  production  of  red  corpuscles,  but  the  very  sudden  changes 
of  this  kind  reported  by  some  authors  as  happening  within  a  few 
hours  must  be  considered  as  apparent  rather  than  real,  and  are 
to  be  explained  by  some  change  in  the  water  contents  or  in  the 
distribution  of  the  blood.* 

Physiology  of  the  Blood  Leucocytes. — The  function  of  the 
blood  leucocytes  has  been  the  subject  of  numerous  investigations, 
particularly  in  connection  with  the  pathology  of  blood  diseases. 
Although  many  hypotheses  liave  been  made  as  the  result  of  this 
work,  it  cannot  be  said  that  we  possess  much  positive  information  as 
to  the  normal  function  of  these  cells  in  the  body.  It  must  be  borne 
in  mind,  in  the  first  place,  that  the  blood  leucocytes  are  not  all  the 
same  histologically,  and  it  may  be  that  their  functions  are  as  diverse 
as  their  morphology.  Various  classifications  have  been  made, 
based  upon  one  or  another  difference  in  microscopical  structure  and 
reaction,  but  at  present  the  terminology  most  used  in  medical 
literature  is  that  adopted  by  Ehrlich.  f  According  to  this  nomen- 
clature, the  white  corpuscles  fall  into  two  main  groups, — the 
lymphocytes  and  the  leucocytes, — and  each  of  these  into  two  or 
more  subgroups.  Thus: 

I.  LYMPHOCYTES.  No  granules  in  the  cell  substance,  and,  though  capable  of 
ameboid  changes  of  form,  this  property  is  not  characteristic  and  prob- 
ably not  sufficient  to  cause  locomotion. 

(a)  Small  lymphocytes  are  about  the  size  of  the  red  corpuscles;  the  nu- 
cleus is  large,  symmetrically  placed,  stains  homogeneously,  and  the 
cytoplasm  is  reduced  to  a  very  small  amount.  They  form  from  20 
to  25  per  cent,  of  all  the  white  corpuscles. 

(6)  Large  lymphocytes.  Two  to  three  times  as  large  as  the  preceding. 
Nucleus  somewhat  eccentric;  the  cytoplasm  is  relatively  more 
abundant  than  in  a,  but  non-granular.  These  forms  exist  only  in 
small  numbers,  forming  1  per  cent,  or  less  of  the  white  corpuscles. 
II.  LEUCOCYTES.  Granules  of  different  sorts  found  in  the  cytoplasm.  Cells 
characteristically  ameboid. 

(a)  Transition  forms  (uninuclear  leucocytes).  Single  large  nucleus,  more 
or  less  lobulated;  cytoplasm  abundant  and  faintly  granulated.  The 
granules  stain  with  neutral  dyes  and  are  therefore  designated  as 
neutrophile  granules.  The  name,  transition  form,  implies  that  these 
leucocytes  represent  an  intermediate  stage  between  the  large  lympho- 
cytes and  the  following  variety,  but  this  belief  is  vigorously  denied 
by  many  competent  hematologists.  This  form  exists  in  small 
numbers — 2  to  10  per  cent,  of  the  total  number  of  white  corpuscles. 

(6)  Polynuchar  or  polymorphonuclear  leucocytes.  The  nucleus  is  seg- 
mented into  lobes  connected  by  narrow  strands.  The  cytoplasm 
is  especially  ameboid  and  is  granular.  The  granules  in  most  cases 
are  neutrophilic  and  small  in- size.  The  typical  cells  of  this  kind 
form  the  bulk  of  the  white  corpuscles  of  the  blood, — 60  to  75  per 

*  For  the  extensive  literature  see  Van  Voornveld,  "Das  Blut  im  Hoch- 
gebirge,"  "Pfliiger's  Archiv,"  92,  1,  1902;  Zuntz  et  al.,  "Hohenklima  und 
Bergwanderungen  in  ihrer  Wirkung  auf  den  Menschen,"  1906.  Douglas  et  al., 
" Philosophical  Transactions,  Royal  Society  of  London,"  B.  vol.  203,  p.  185, 1913. 

t  Ehrlich,  "Die  Anaernie,"  1898;  see  also  Seemann,  "Ergebnisse  der 
Physiologic,"  3,  part  i,  1904. 


444  BLOOD    AND    LYMPH. 

cent.  Eosinophilic  leucocytes  form  a  subgroup  of  this  variety.  'Itiey 
have  a  similar  segmented  nucleus,  but  the  cytoplasm  contains  nu- 
merous coarse  granules  that  stain  in  acid  dyes,  such  as  eosin,  whence 
the  name. 

VP)  Mast  cells.  These  peculiar  cells  exist  in  very  small  numbers  under 
normal  conditions, — less  than  1  per  cent,  of  the  total  number  of 
white  corpuscles.  They  have  a  polymorphic  nucleus  like  the  pre- 
ceding group,  but  differ  in  the  fact  that  the  granules  in  the  cyto- 
plasm are  strongly  basophilic, — that  is,  will  stain  only  with  basic 
dyes,  such  as  thionin. 

Current  opinions  vary  greatly  in  regard  to  the  origin  and 
relations  of  these  different  forms  of  white  blood-corpuscles,  almost 
every  writer  proposing  some  special  hypothesis  to  indicate  his 
particular  point  of  view.*  In  general,  however,  it  may  be  said 
that  the  divergent  views  fall  under  two  heads.  First,  the  so- 
called  dualistic  theory,  according  to  which  there  are  two  sources 
of  origin  for  these  cells,  namely,  the  lymphoblasts  of  the  lymph 
nodes  which  give  rise  to  the  small  lymphocytes  and  the  myeloblasts 
of  the  bone-marrow,  which  give  rise  to  the  granular  leucocytes  of 
the  blood  and  probably  also  seive  as  the  parent  form  for  the  large 
mononuclear  leucocytes  and  transitional  forms.  Second,  the 
Unitarian  or  monophyletic  theory,  according  to  which  all  the  white 
blood-corpuscles  arise  from  a  single  form  or  variety  of  parent  cells 
that  has  the  characteristics  of  a  large  or  small  lymphocyte. 
Most  authors  perhaps  believe  that  the  various  forms  as  they  exist 
in  the  blood  are  from  an  anatomical  standpoint  permanently 
differentiated.  Such  a  view  implies,  on  the  physiological  side,  that 
each  form  has  some  special  functional  activity  of  its  own.  Little 
or  no  progress  has  been  made,  however,  in  discovering  the  specific 
physiology  of  the  various  leucocytes. 

Variations  in  Number. — Under  normal  conditions  the  total 
number  of  leucocytes  may  show  considerable  variation;  the  aver- 
age number  in  health  varies  usually  between  5000  and  7000 
per  cubic  millimeter.  A  distinct  increase  in  number  is  designated 
as  a  condition  of  leucocytosis,  a  marked  diminution  as  a  condition  of 
leucopenia.  Leucocytosis  occurs  under  various  normal  conditions, 
such  as  digestion,  exercise  or  cold  baths,  pregnancy,  etc.  The 
variations,  relative  or  absolute,  under  pathological  conditions,  have 
been  studied  with  exhaustive  care  as  an  aid  to  diagnosis  and  classi- 
fication. 

Functions  of  the  Leucocytes. — Perhaps  the  most  striking 
property  of  the  leucocytes  as  a  class  is  their  power  of  making 
ameboid  movements, — a  characteristic  which  has  gained  for  them 
the  sobriquet  of  "wandering"  cells.  By  virtue  of  this  property 
some  of  them  are  able  to  migrate  through  the  walls  of  blood  capil- 
laries into  the  surrounding  tissues.  This  process  of  migration  takes 

*  See  Weidenreich  for  summary,  "Ergebnisse  der  Anatomic  und  Entwickel- 
ungsgeschichte,"  vol.  19,  part  n  (1909),  1911. 


GENERAL  PROPERTIES:  THE  CORPUSCLES.         445 

place  normally,  but  is  vastly  accelerated  under  pathological  con- 
ditions. As  to  the  function  or  functions  fulfilled  by  the  leucocytec, 
numerous  suggestions  have  been  made,  some  of  which  may  be 
stated  in  brief  form  as  follows:  (1)  They  protect  the  body  from 
pathogenic  bacteria  and  other  foreign  cells  or  organisms.  In 
explanation  of  this  action  it  has  been  suggested  that  they  may 
either  ingest  bacteria,  and  thus  destroy  them  directly,  or  they 
may  form  certain  substances,  bacteriolysins,  that  destroy  the 
bacteria.  The  wonderful  protective  adaptation  of  the  body  des- 
ignated by  the  term  "biological  reaction"  has  already  been  referred 
to  (p.  425).  The  formation  of  immune  substances  in  the  blood  is 
attributed,  in  part  at  least,  to  the  leucocytes.  Leucocytes  that 
act  by  ingesting  the  bacteria  are  spoken  of  as  "  phagocytes  "  (updyeeVj 
to  eat;  KUTOZ,  cell).  This  theory  of  their  function  is  usually 
designated  as  the  "phagocytosis  theory  of  Metchnikoff";  it  is 
founded  upon  the  fact  that  the  ameboid  leucocytes  are  known  to 
ingest  foreign  particles,  including  bacteria,  with  which  they  come 
in  contact.  The  leucocytes  which  seem  especially  adapted  to 
attack  bacteria  are  the  polymorphonuclear  variety,  designated 
by  Metchnikoff  as  microphags.  This  power  of  the  leucocytes  to 
ingest  bacteria  depends,  according  to  Wright,  upon  the  presence 
in  the  plasma  of  certain  substances  designated  as  opsonins  (from 
opso'no,  I  prepare  food  for),  which  sensitize  or  in  some  way  prepare 
the  bacteria  so  that  they  are  attacked  by  the  leucocytes.  These 
opsonins,  like  the  cytotoxins,  belong  to  the  group  of  antibodies, 
and  may  be  called  into  existence  or  increased  in  amount  by  the 
injection  into  the  body  of  suitable  bacteria  or  their  products.* 
(2)  They  aid  in  the  absorption  of  fats  from  the  intestine.  (3)  They 
aid  in  the  absorption  of  peptones  from  the  intestine.  (4)  They  take 
part  in  the  process  of  blood  coagulation.  (5)  They  help  to  main- 
tain the  normal  composition  of  the  blood-plasma  in  proteins.  The 
blood  proteins  are  peculiar,  and  they  are  not  formed  directly  from 
the  digested  food.  It  is  possible  that  the  leucocytes,  which  are 
the  only  typical  cells  in  the  blood,  aid  in  keeping  up  the  normal 
supply  of  proteins.  From  this  standpoint  they  might  be  regarded 
in  fact  as  unicellular  glands,  the  products  of  their  metabolism 
serving  to  maintain  the  normal  composition  of  the  blood-plasma. 
The  formation  of  granules  within  the  substance  of  the  eosinophiles 
offers  a  suggestive  analogy  to  the  accumulation  of  zymogen 
granules  in  glandular  cells. 

Physiology  of  the  Blood  Plates.— The  blood  plates  are  disc- 
shaped  bodies  which  appear  as  short  rods  or  as  circular  or  elliptic 
plates,  according  as  they  are  seen  on  edge  or  on  the  flat  face. 
They  vary  in  diameter  on  the  flat  face,  but  are  in  all  cases  much 
general  discussion  of  opsonins,  see  Hektoen,  "Science," 


446  BLOOD    AND    LYMPH. 

smaller  than  the  red  corpuscles.  When  removed  from  the  circu- 
lating blood  they  are  known  to  disintegrate  very  rapidly.  This 
peculiarity,  in  fact,  prevented  them  from  being  discovered  for  a  long 
time  after  the  blood  had  been  studied  microscopically.  It  has  been 
shown  that  they  are  formed  elements,  and  not  simply  precipitates 
from  the  plasma,  as  was  suggested  at  one  time.  The  theory  of 
Hay  em,  their  real  discoverer,  that  they  develop  into  red  corpuscles 
may  also  be  considered  as  erroneous.  There  is  considerable  evi- 
dence to  show  that  in  shed  blood  they  take  part  in  the  process  of 
coagulation.  The  nature  of  this  evidence  will  be  described  later. 
On  account  of  their  small  size  the  structure  of  the  blood  plates 
is  not  satisfactorily  known.  Deetjen*  has  demonstrated  that  they 
are  capable  of  ameboid  movements.  When  removed  from  the 
blood-vessels  to  a  glass  slide  they  usually  agglutinate  into  larger 
or  smaller  masses,  swell,  and  disintegrate,  but  if  received  upon  a 
surface  of  agar-agar  which  has  been  made  up  with  physiological 
saline,  together  with  some  sodium  metaphosphate  (NaPO3),  they 
flatten  out,  show  a  central  granular  portion  and  a  peripheral  clear 
layer,  and  may  make  quite  active  ameboid  movements.  Deetjen 
claims  also  that  they  possess  a  distinct  nucleus.  This  latter 
statement  is  perhaps  doubtful,  as  other  observers  report  that  the 
material  which  stains  like  a  nucleus  is  present  as  separate  granules 
in  the  interior  of  the  plate.  These  granules,  though  possibly  of 
nuclear  material,  do  not  have  the  morphological  appearance  of  a 
cell  nucleus.  It  remains,  therefore,  uncertain  whether  the  blood 
plates  are  to  be  considered  as  independent  cells  or  as  fragments 
of  cells.  The  origin  or  histogenesis  of  the  plates  has  been  studied 
by  many  observers.  Numerous 'hypotheses  have  been  suggested; 
that  they  originate  from  the  nuclei  of  the  polynuclear  leucocytes; 
that  they  are  extruded  remnants  of  the  nuclei  of  the  young  red 
blood-corpuscles;  that  they  are  detached  pieces  of  the  cytoplasm 
of  the  giant  cells  (megakaryocytes)  of  the  bone-marrow,  etc.,  but 
no  one  of  the  hypotheses  proposed  has  found  general  acceptance. 
The  origin,  fate  and  function  of  these  interesting  bodies  are  still 
open  questions  in  spite  of  the  great  amount  of  investigation  de- 
voted to  the  subject.  The  normal  number  of  the  plates  in  the 
circulating  blood  is  large,  but  the  estimates  made  vary  somewhat 
with  the  method  used.f  When  the  blood  is  shed  the  plates 

*  "Virchow's  rArchiv  f.  path.  Anat.  u.  Physiol.,"  164,  239,  1901,  also 
Zeitschrift  f.  physiol.  chemie,  63/1,  1909. 

f  For  a  summary  of  the  literature  and  methods,  consult  Kemp,  "Journal 
of  the  American  Medical  Association,"  April  7  and  14,  1906;  Pratt,  ibid., 
Dec.  30,  1905,  and  Wright  and  Kinnicutt,  "Transactions  of  Assoc.  of  Am. 
Physicians,"  May,  1901.  The  preservative  solution  recommended  by  Pratt 
consists  of  sodium  metaphosphate,  2  grams;  sodium  chlorid,  0.9  gram;  water, 
100  c.c.  That  preferred  by  Kemp  is,  formalin  (40  per  cent,  aqueous  solution 
of  formaldehyd),  10  c.c.;  sodium  chlorid  (1  per  cent,  solution),  150  c.c.,  while 
Wright  employs  a  solution  of  cresyl  blue  and  potassium  cyanid. 


GENERAL    PROPERTIES:    THE    CORPUSCLES.  447 

agglutinate  quickly  into  masses  which  soon  disintegrate  more  or 
less  completely,  and  it  is  necessary  therefore  in  counting  them  to 
mix  the  blood  with  a  fixing  solution  which  will  coagulate  the  plates 
and  keep  them  from  adhering  together.  Solutions  that  precipitate 
the  calcium  of  the  blood-plasma,  such  as  sodium  oxalate,  have  the 
effect  of  fixing  the  plates.  The  average  number  of  plates  may  be 
given  as  300,000  per  cubic  millimeter.  The  extremes  reported 
vary  from  200,000  or  250,000  to  778,000.  Under  certain  patho- 
logical conditions,  especially  in  pernicious  anemia  and  lymphatic 
leucemia,  their  number  is  greatly  reduced,  while  in  the  acute 
infectious  diseases  there  is  said  to  be  a  diminution  in  number 
during  the  period  of  fever,  followed  by  a  marked  increase  beyond 
the  normal  during  the  period  of  convalescence.  A  number  of 
observers  have  stated  that  in  hemorrhagic  diseases  in  which  there 
is  delayed  coagulation  and  tendency  to  bleed  there  may  be  a  great 
reduction  in  the  number  of  platelets.  Duke*  states  that  in  such 
cases  transfusion  of  blood  from  a  normal  person  removes  the  hemor- 
rhagic tendency,  while  increasing  markedly  the  number  of  plate- 
lets. But  in  three  days  the  number  of  platelets  again  falls  to  a 
low  level,  and  simultaneously  there  is  again  a  tendency  to  spon- 
taneous bleeding.  The  observation  is  of  interest  as  indicating 
that  the  life  history  of  the  platelets  in  the  circulation  is  probably 
very  brief. 

*  Duke,  "Journal  of  the  Amer.  Med.  Assoc.,"  55,  p.  1185,  1910. 


CHAPTER  XXIII. 

CHEMICAL  COMPOSITION  OF  THE  BLOOD-PLASMA?   CO- 
AGULATION?  QUANTITY  OF  BLOOD;  REGENERA- 
TION AFTER  HEMORRHAGE. 


Composition  of  the  Plasma  and  Corpuscles. — Blood  (plasma 
and  corpuscles)  contains  a  great  variety  of  substances,  as  might  be 
inferred  from  its  double  relations  to  the  tissues  as  a  source  of 
nutrition  and  as  a  means  of  removing  the  waste  products  of  their 
functional  activity.  The  constituents  that  may  be  present  in 
normal  blood-plasma  are  in  part  definitely  known  and  in  part 
entirely  unknown  from  a  chemical  standpoint.  Some  idea  of  the 
complexity  of  the  composition  may  be  obtained  from  the  following 
table: 

COMPOSITION    OF    THE    BLOOD-PLASMA. 
WATER,  OXYGEN,  CARBON  DIOXID,  NITROGEN. 
(  Fibrinogen. 

<  Paraglobuli 

I  Serum-albumin. 


Extractives — that  is,  substances  other 
than  proteins  that  may  be  ex- 
tracted from  the  dried  residue  by 
water,  alcohol,  or  ether. 


Salts. 


Fats. 

Sugar. 

Urea. 

Uric  acid. 

Creatin. 

Creatinin. 

Jecorin. 

Glucuronic  acid. 

Lecithin. 

Cholesterin. 

Lactic  acid. 

fChlorids         ^| 
J  Carbonates 


of 


j  Sulphates 
( Phosphates 

Internal  secretions. 


1  Sodium. 
Potassium. 
Calcium. 
Magnesium. 
Iron. 


Enzymes  and  special  substances , 


,  etc. 

Prothrombin. 
Antithrombin. 
Epinephrin. 

Immune  bodies  (Amboceptors). 
Complements. 
^  Opsonins. 

A  number  of  detailed  chemical  analyses  of  the  blood  of  different 
animals,  so  far  as  its  constituents  can  be  determined  by  analytical 

448 


CHEMICAL    COMPOSITION    OF    BLOOD-PLASMA.  449 

methods,  have  been  reported  at  different  times.  The  following 

table,  taken  from  Abderhalden,*  and  showing  the  composition  of 
dogs'  blood,  may  serve  as  an  example: 

1000  PARTS,  BT  1000  PARTS,  BY  1000  PARTS,  BY 
WEIGHT,  OF  BLOOD  WEIGHT,  OF  SK-      WEIGHT,  OF  CORPUS- 
CONTAIN  RUM  CONTAIN  CLES  CONTAIN 

Water   810.05  923.98  644.26 

Solids 189.95  76.02  355.75 

Hemoglobin 133.4  327.52 

Protein 39.68  60.14  9.918 

Sugar 1.09  1.82 

Cholesterin 1.298.  0.709  2.155 

Lecithin   2.052  1.699  2.568 

Fat 0.631  1.051 

Fatty  acids 0.759  1.221  0.088 

Phosphoric  acid: 

as  nuclein 0.054  0.016  0.110 

N^O 3.675  4.263  2.821 

K2O 0.251  0.226  0.289 

FejO, 0.641  1.573 

CaO 0.062  0.113 

MgO 0.052  0.040  0.071 

Cl 2.935  4.023  1.352 

P,O, 0.809  0.242  1.635 

Inorganic : 


rgan 
205- 


P2O5 0.576  0.080  1.298 

The  same  constituents  in  much  the  same  proportions  are  found 
in  the  blood  of  all  the  mammalia  examined.  The  amount  of  protein 
in  the  serum  is  greater  in  some  cases  than  in  others, — in  the  dog, 
for  instance,  according  to  Abderhalden's  analyses,  the  protein 
amounts  to  only  6  per  cent.,  while  in  the  horse  it  may  be  7  or  8  per 
cent.  So  also  there  are  small  variations  in  the  amount  of  choles- 
terin,  sugar,  and  other  constituents,  but,  on  the  whole,  the  composi- 
tion of  the  liquid  part  of  the  blood,  blood-serum  or  blood-plasma, 
is  remarkably  uniform  so  far  as  chemical  analyses  go.  We  know, 
however,  that  the  physiological  properties  of  mammalian  serum  may 
be  very  different  indeed;  that  the  serum  of  a  dog,  for  instance,  will 
kill  a  rabbit  when  injected  into  its  vessels.  Such  physiological  dif- 
ferences as  this,  however,  depend  upon  constituents  which  can  not 
be  determined  at  present  by  chemical  means.  The  chemical  com- 
position of  the  blood-serum  differs  from  that  of  the  red  corpuscles  in 
a  number  of  respects  in  addition  to  the  presence  of  hemoglobin  in 
the  latter.  The  corpuscles  contain  no  sugar  nor  fat,  a  larger  amount 
of  cholesterin,  lecithin,  phosphoric  acid,  and  potassium,  and  less 
sodium  and  chlorin.  The  red  corpuscles  of  different  mammalia 
show  a  remarkable  variation  in  the  amount  of  potassium  salts 
contained.  Thus,  according  to  Brandenburg,  1000  parts  by  weight 
of  the  red  corpuscles  contain  the  following  amounts  of  K2O  in 
different  mammalia:  Cat,  0.258:  dog,  0.257;  man,  4.294;  horse, 
4.957;  rabbit,  5.229. 

*  "Zeitschrift  f.  physiologische  Chemie,"  25,  88,  1898. 
29 


450  BLOOD    AND    LYMPH. 

Proteins  of  the  Blood-plasma. — The  general  properties  and 
reactions  of  proteins  and  the  related  compounds,  as  well  as  a  classi- 
fication of  those  occurring  in  the  animal  body,  are  described  briefly 
in  the  Appendix.  This  description  should  be  read  before  attempt- 
ing to  study  the  proteins  of  the  plasma  and  the  part  they  take  in 
coagulation.  Three  proteins  are  usually  described  as  existing  in  the 
plasma  of  circulating  blood, — namely,  fibrinogen,  paraglobulin, 
or,  as  it  is  sometimes  called,  "serum-globulin,"  and  serum-albumin. 
The  first  two  of  these  proteins,  fibrinogen  and  paraglobulin,  belong 
to  the  group  of  globulins,  and  hence  have  many  properties  in  com- 
mon. Serum-albumin  belongs  to  the  group  of  albumins,  of 
which  egg-albumin  constitutes  another  member. 

Serum-albumin. — This  substance  is  a  typical  protein.  It  can  be 
obtained  readily  in  crystalline  form  from  the  horse's  blood.  Its 
percentage  composition,  according  to  Michel,  is  as  follows:  0, 53.08; 
H,  7.10;  N,  15.93;  S,  1.90;  O,  21.96. 

Its  molecular  composition,  according  to  Schmiedeberg,*  may  be 
represented  by  C78H122N20SO24  or  some  multiple  of  this  formula. 
Serum-albumin  shows  the  general  reactions  of  the  native  albumins. 
One  of  its  most  useful  reactions  is  its  behavior  toward  magnesium 
sulphate  and  ammonium  sulphate.  Serum-albumin  usually  occurs  in 
the  body-liquids  together  with  the  globulins,  as  is  the  case  in  blood. 
If  such  a  liquid  is  thoroughly  saturated  with  solid  magnesium  sul- 
phate or  half  saturated  with  ammonium  sulphate,  the  globulins 
are  precipitated  completely,  while  the  albumin  is  not  affected. 
So  far  as  the  blood  and  similar  liquids  are  concerned,  a  definition 
of  serum-albumin  might  be  given  by  saying  that  it  comprises  all 
the  proteins  not  precipitated  by  saturation  with  magnesium  sul- 
phate or  by  half  saturation  with  ammonium  sulphate.  When  its- 
solutions  have  a  neutral  or  an  acid  reaction,  serum-albumin  is 
precipitated  in  an  insoluble  form  by  heating  the  solution  above  a 
certain  degree.  Precipitates  produced  in  this  way  by  heating 
solutions  of  proteins  are  spoken  of  as  coagulations — heat  coagula- 
tions— and  the  exact  temperature  at  which  coagulation  occurs 
is  to  a  certain  extent  characteristic  for  each  protein.  The  tem- 
perature of  coagulation  of  serum-albumin  is  usually  given  at  from 
70°  to  75°  C.,  but  it  varies  greatly  with  the  conditions, — for  in- 
stance, with  the  reaction  of  the  solution,  its  concentration  in  salts, 
or  with  the  nature  of  the  salts  present.  It  has  been  asserted, 
in  fact,  that  careful  heating  under  proper  conditions  gives  separate 
coagulations  at  three  different  temperatures, — namely,  73°,  77°, 
and  84°  C., — indicating  the  possibility  that  what  is  called  "serum- 
albumin"  may  be  a  mixture  of  three  proteins.  Serum-albumin 
occurs  in  blood-plasma  and  -blood-serum,  in  lymph,  and  in  the 
different  normal  and  pathological  exudations  found  in  the  body, 
*  "Archiv  f.  exper.  Pathol.  u.  Pharmakol.,"  39,  1,  1897. 


CHEMICAL    COMPOSITION    OF    BLOOD-PLASMA.  451 

such  as  pericardial  liquid,  hydrocele  fluid,  etc.  The  amount  of 
serum-albumin  in  the  blood  varies  in  different  animals,  ranging 
among  the  mammalia  from  2.67  per  cent,  in  the  horse  to  4.52  per 
cent,  in  man.  In  some  of  the  cold-blooded  animals  it  occurs  in 
surprisingly  small  quantities, — 0.36  to  0.69  per  cent. 

Paraglobulin,  which  belongs  to  the  group  of  globulins,  exhibits 
the  general  reactions  characteristic  of  the  group.  As  stated  above, 
it  is  completely  precipitated  from  its  solutions  by  saturation  with 
magnesium  sulphate  or  by  ^half  saturation  with  ammonium  sul- 
phate. It  is  incompletely  precipitated  by  saturation  with  common 
salt  (NaCl).  In  neutral  or  feebly  acid  solutions  it  coagulates  upon 
heating  to  75°  C.  Hammarsten  gives  its  percentage  composition 
as:  C,  52.71;  H,  7.01;  N,  15.85;  S,  1.11;  O,  23.32.  Schmiedeberg 
gives  it  a  molecular  composition  corresponding  to  the  formula 
C117H182N30SO38  +  iH2O.  Paraglobulin  occurs  in  blood,  in  lymph, 
and  in  the  normal  and  pathological  exudations.  The  amount  of 
paraglobulin  present  in  blood  varies  in  different  animals.  Among 
the  mammalia  the  amount  ranges  from  1.78  per  cent,  in  rabbits  to 
4.56  per  cent,  in  the  horse.  In  human  blood  it  is  given  at  3.10 
per  cent.,  being  less  in  amount,  therefore,  than  the  serum-albumin, 
It  is  usually  stated  that  more  of  this  protein  is  found  in  the  serum 
than  in  the  plasma.  This  fact  is  explained  by  supposing  that  dur- 
ing coagulation  some  of  the  leucocytes  disintegrate  and  part  of 
their  substance  passes  into  solution  as  a  globulin  identical  with  or 
closely  resembling  paraglobulin.  Paraglobulin  as  obtained  from 
blood-serum  by  half  saturation  with  ammonium  sulphate  or  full 
saturation  with  magnesium  sulphate  does  not  behave  like  a  chem- 
ical individual.  Portions  of  it,  for  instance,  are  precipitated  by 
CO2  or  by  dialysis,  and  portions  are  not  so  precipitated.  Recently, 
therefore,  it  has  been  assumed  that  paraglobulin  is  in  reality  a 
mixture  of  two  or  possibly  three  different,  although  related,  pro- 
teins. The  separation  usually  given  is  into  euglobulin  and  pseu- 
doglobulin,  euglobulin  being  the  portion  precipitated  by  ammo- 
nium sulphate  when  added  to  one-third  saturation  (28  to  33  per 
cent.),  and  pseudoglobulin  the  portion  precipitated  only  by  one- 
half  saturation  (34  to  50  per  cent.).  The  latter  portion  shows 
properties  more  nearly  related  to  the  albumins.*  The  whole  basis 
of  classification  is,  however,  unsatisfactory  and  provisional  (see 
appendix) . 

Fibrinogen  is  a  protein  belonging  to  the  globulin  class  and  ex- 
hibiting all  the  general  reactions  of  this  group.  It  is  distinguished 
from  paraglobulin  by  a  number  of  special  reactions;  for  example, 

*  Forges  and  Spiro,  "Beitrage  zur  chem.  Physiol.  u.  Pathol.,"  3,  277 
1903;  and  Freund  and  Joachim,  "Zeitschrift  f.  physiologische  Chemie,"  36, 
407,  1902. 


452  BLOOD    AND    LYMPH. 

its  temperature  of  heat  coagulation  is  much  lower  (56°  to  60°  C.), 
and  it  is  completely  thrown  down  from  its  solutions  by  saturation 
with  sodium  chlorid  as  well  as  with  magnesium  sulphate.  Its  most 
important  and  distinctive  reaction  is,  however,  that  under  proper 
conditions  it  gives  rise  to  an  insoluble  protein,  fibrin,  whose  forma- 
tion is  the  essential  phenomenon  in  the  coagulation  of  blood. 
Fibrinogen  has  a  percentage  composition,  according  to  Hammar- 
sten,  of:  0,52.93;  H,  6.90;  N,  16.66;  S,1.25;  O,  22.26;  while  its 
molecular  composition,  according  to  Schmiedeberg,  is  indicated  by 
the  formula  C108H162N30S034. 

Fibrinogen  is  found  in  blood-plasma,  lymph,  and  in  some  cases, 
though  not  always,  in  the  normal  and  pathological  exudations.  It 
is  absent  from  blood-serum,  being  used  up  during  the  process  of 
clotting.  It  occurs  in  very  small  quantities  in  blood,  compared 
with  the  other  proteins.  Estimates  of  the  amount  of  fibrin,  which 
cannot  differ  very  much  from  the  fibrinogen,  show  that  in  human 
blood  it  varies  from  0.22  to  0.4  per  cent. ;  in  horse's  blood  it  may 
be  more  abundant, — 0.65  per  cent.  There  is  some  evidence  to 
indicate  that  the  fibrinogen  is  produced  in  the  liver,  or  at  any  rate 
that  this  organ  is  concerned  in  some  way  in  its  production.  Thus 
it  is  stated  that  extirpation  of  the  liver  in  the  dog,  after  establishing 
an  Eck  fistula,  is  followed  by  a  rapid  disappearance  of  the  fibrino- 
gen of  the  blood.*  In  phosphorus  poisoning,  and  particularly  in 
chloroform  poisoning,  which  is  attended  by  an  extensive  necrosis 
of  the  central  portions  of  the  liver  lobules,  the  amount  of  fibrinogen 
in  the  blood  is  rapidly  reduced,  f  and  simultaneously,  as  we  should 
expect,  the  blood  loses  more  or  less  completely  its  power  of  clotting. 
Finally  it  has  been  noted  that  if  the  blood  of  a  dog  is  withdrawn 
in  separate  portions,  defibrinated  and  reinjected  into  the  circula- 
tion, the  missing  fibrinogen  is  quickly  regenerated  in  a  normal 
animal,  while  in  one  with  its  liver  thrown  out  of  function  this  re- 
generation does  not  take  placet 

The  following  table  §  gives  some  results  of  analyses  of  blood 
which  indicate  the  average  amounts  of  the  different  proteins 
in  the  blood-plasma  of  several  animals.  The  figures  give  the  weight 
of  the  protein  in  grams  for  100  c.c.  of  plasma. 

SERUM- 
TOTAL  PROTEINS.     ALBUMIN.     PARAGLOBULIN.     FIBRINOGEN. 

Man..  ..7.26  4.01*  2.83  0.42 

Dog...; 6.03  3.17  2.26  0.60 

Sheep 7.29  3.83  3.00  0.46 

Horse 8.04  2.80  4.79  0.45 

Pig 8.05  4.42  2.98  0.65 


Lewinski,  "Pfliiger's  Archiv,"  100,  611,  1903. 


COAGULATION.  453 

Other  Proteins  of  the  Blood-serum  or  Blood-plasma. — From  time  to  time 
other  protein  bodies  have  been  described  in  the  serum  or  plasma  of  the  blood. 
In  the  serum  after  coagulation  Hammarsten  has  obtained  a  globulin  body, 
fibrin-globulin,  which  he  supposes  may  be  split  off  from  the  fibrinogen  dur- 
ing the  act  of  clotting.  Faust  describes  an  albuminoid  substance,  glutelin, 
which  is  present  in  the  blood  and  is  usually  precipitated  together  with  the 
paraglobulin.  A  number  of  observers  have  noted  the  existence  in  blood 
of  a  protein  not  coagulated  by  heat.  By  some  authors  this  has  been  de- 
scribed as  a  peptone  or  an  albumose  (Langstein),  by  others  as  an  ovomucoid 
(Zanetti),  and  by  others  still  (Chabrie)  as  a  peculiar  protein  for  which  the 
name  albumon  has  been  proposed.  By  others  still,  this  non-coagulable  pro- 
tein obtained  from  serum  or  plasma  has  been  explained  as  an  artificial 
product  arising  from  the  globulins  of  the  blood  during  the  process  of  remov- 
ing the  coagulable  proteins  by  heating.  So,  too,  nucleoprotein  substances 
have  been  described  in  the  blood-serum  by  several  observers,  most  recently  by 
Freund  and  Joachim.  It  is  quite  possible,  however,  that  the  substance  de- 
scribed as  nucleoprotein  is  in  reality  a  mixture  or  combination  of  lecithin  and 
protein.  Most  of  the  protein  when  precipitated  from  the  blood  carries  down 
with  it  some  lecithin,  and  will  therefore  show  a  reaction  for  phosphorus.  It 
can  be  shown  that  the  phosphorus  present  is,  in  most  cases  at  least,  remov- 
able by  boiling  with  alcohol,  and  there  is  at  present  no  entirely  satisfactory 
proof  that  nucleoprotein  exists  in  the  blood. 

Coagulation  of  Blood. — One  of  the  most  striking  properties  of 
blood  is  its  power  of  clotting  or  coagulating  shortly  after  it  escapes 
from  the  blood-vessels.  The  general  changes  in  the  blood  during 
this  process  are  easily  followed.  At  first  perfectly  fluid,  in  a  few 
minutes  it  becomes  viscous  and  then  sets  into  a  soft  jelly  which 
quickly  becomes  firmer,  so  that  the  vessel  containing  it  may  be 
inverted  without  spilling  the  blood.  The  clot  continues  to  grow 
more  compact  and  gradually  shrinks  in  volume,  pressing  out  a 
smaller  or  larger  quantity  of  a  clear,  faintly  yellow  liquid  to  which 
the  name  blood-serum  is  given.  The  essential  part  of  the  clot  is  the 
fibrin.  Fibrin  is  an  insoluble  protein  not  found  in  normal  blood. 
In  shed  blood,  and  under  certain  conditions  in  blood  while  still  in  the 
blood-vessels,  this  fibrin  is  formed  from  the  soluble  fibrinogen. 
The  deposition  of  the  fibrin  is  peculiar.  As  seen  in  ordinary 
microscopical  preparations,  the  fibrin  forms  very  delicate  threads 
which  are  united  to  make  a  fine  reticulum.  When  the  process  is 
observed  with  the  aid  of  the  ultramicroscope  it  can  be  seen  that 
the  fibrin  is  deposited  in  the  form  of  very  fine  needles,  which  have 
the  appearance  of  acicular  crystals.*  When  the  process  of  clot- 
ting is  very  slow  the  needles  may  remain  separate  for  a  long  time 
until  their  number  is  greatly  increased,  but  in  normal  clotting  the 
process,  once  it  has  started,  is  completed  quite  rapidly,  the  final 
result  being  a  dense  network  or  meshwork  of  the  fibrin  needles 
(Fig.  186).  This  form  of  precipitation  of  a  colloid  solution,  or 
the  formation  of  a  hydrogel  from  a  hydrosol,  is  unique  so  far  as 
our  knowledge  goes.  Solutions  of  fibrinogen  may  be  precipitated, 

*  See  Stiibel,  "Pfluger's  Archiv  f.  d.  ges.  Physiologic,"  156,  361,  1914;  and 
HoweU,  "American  Journal  of  Physiology,"  35,  143,  1914. 


454  BLOOD    AND    LYMPH. 

like  solutions  of  other  proteins,  in  a  great  variety  of  ways,  by 
heat,  by  acids,  by  neutral  salts,  etc.,  but  in  these  cases  the  col- 
loidal particles  of  the  solution  are  simply  aggregated  into  larger 
clumps  or  masses.  The  deposition  of  the  fibrinogen  in  the  form 
of  needles  takes  place  only  under  the  influence  of  thrombin,  the 
substance  which  causes  normal  clotting,  as  will  be  described 
further  on.  When  the  clot  is  formed  it  shrinks  or  contracts 
rapidly  in  all  directions,  especially  if  freed  from  contact  with  the 
walls  of  the  containing  vessel.  If  the  blood  has  not  been  dis- 
turbed during  the  act  of  clotting,  the  red  corpuscles  are  caught 
in  the  fine  fibrin  meshwork,  and  as  the  clot  shrinks  these  cor- 
puscles are  held  more  firmly,  only  the  clear  liquid  of  the  blood 


Fig.  186. — The  fibrin  needles  formed  in  the  clotting  of  blood.  Plasma  of  oxalated  dog's 
blood  clotted  by  thrombin.  The  photographs  show  the  needles  as  seen  with  the  ultrami- 
croscope.  A,  photographed  by  sun-light;  B,  by  arc-light.  Only  the  needles  lying  in  the  focal 
plane  are  seen  distinctly. 

being  squeezed  out,  so  that  it  is  possible  to  get  specimens  of 
serum  containing  few  or  no  red  corpuscles.  The  leucocytes,  on 
the  contrary,  although  they  are  also  caught  at  first  in  the  forming 
meshwork  of  fibrin,  may  readily  pass  out  into  the  serum  in  the  later 
stages  of  clotting,  on  account  of  their  power  of  making  ameboid 
movements.  If  the  blood  has  been  agitated  during  the  process  of 
clotting,  the  delicate  mesh  will  be  broken  in  places  and  the  serum 
will  be  more  or  less  bloody — that  is,  it  will  contain  numerous  red 
corpuscles.  If  during  the  time  of  clotting  the  blood  is  vigorously 
whipped  with  a  bundle  of  fine  rods,  all  the  fibrin  is  deposited  as  a 
stringy  mass  upon  the  whip,  and  the  remaining  liquid  part  con- 


COAGULATION.  455 

sists  of  serum  plus  the  blood  corpuscles.  Blood  that  has  been 
whipped  in  this  way  is  known  as  "defibrinated  blood."  It  re- 
sembles normal  blood  in  appearance,  but  is  different  in  its  com- 
position; it  cannot  clot  again.  The  physiological  value  of  clotting 
is  that  it  stops  hemorrhages  by  closing  the  openings  of  the  wounded 
blood-vessels. 

Time  of  Clotting. — In  human  blood  the  time  necessary  for  clot- 
ting varies  greatly,  according  to  the  conditions  to  which  the  blood 
is  subjected  after  shedding.  Blood  allowed  to  flow  from  a  wound 
into  a  receiving  vessel  may  clot  within  a  few  (3  to  10)  minutes 
according  to  the  amount  of  blood  drawn,  the  extent  of  surface 
with  which  it  comes  into  contact,  the  condition  of  the  receiving 
vessel,  etc.  The  same  blood  taken  from  a  vein  into  a  clean 
syringe,  by  the  operation  of  venepuncture,  and  emptied  into  a 
perfectly  clean  vessel,  may  require  from  30  to  40  minutes  before  it 
jellies  throughout.  If  the  surfaces  with  which  the  shed  blood 
comes  into  contact  are  coated  with  oil  or  vaseline,  clotting  may  be 
delayed  for  even  a  longer  time.  These  differences  may  be  under- 
stood when  we  remember  that  clotting  is  a  complicated  process 
which  involves  a  series  of  preliminary  changes  or  reactions  in  the 
blood.  These  latter  reactions  may  be  accelerated  or  retarded 
according  to  the  conditions  under  which  the  blood  is  placed.  For 
clinical  purposes  various  simple  methods  have  been  devised  to 
determine  the  clotting  time  with  a  drop  or  two  of  blood,  such  as 
may  be  obtained  by  pricking  the  ear  or  the  finger.*  In  using  such 
methods  to  compare  normal  with  pathological  bloods,  it  is  necessary 
to  employ  always  the  same  method  and  to  keep  the  conditions  as 
uniform  as  possible.  Pathological  conditions  are  known  in  which 
the  coagulation  time  of  the  blood  is  greatly  prolonged.  This  is 
notably  the  case  in  the  class  of  persons  known  as  bleeders  (henKH 
philics) ,  whose  blood  clots  so  slowly  that  even  small  wounds  often 
cause  a  fatal  hemorrhage.  True  congenital  hemophilia  is  trans- 
missible by  heredity,  and  exhibits  the  interesting  peculiarity  that, 
as  a  rule,  it  affects  only  the  male,  but  is  transmitted  only  through 
the  female.  That  is  to  say,  a  man  who  is  hemophilic  does  not 
transmit  the  defect  to  his  sons  or  his  daughters,  but  the  latter  may 
carry  the  defect  in  a  latent  form  and  transmit  it  actively  to  their 
sons.  The  mortality  from  this  condition  is  very  high.  On  the 
other  hand,  cases  are  known  in  which  the  coagulability  of  the 
blood  is  so  much  augmented  that  spontaneous  clotting  occurs  at 
places  within  the  veins  or  arteries  (thrombosis),  leading  to  serious 
complications  or  even  to  death.  To  throw  light  on  these  cases  it  is 

*  For  clinical  methods  of  determining  the  coagulation  time  with  a  drop 
or  two  of  blood,  reference  may  be  made  to'  the  manuals  of  clinical  diagnosis. 
See  Addis,  "Quarterly  Journal  of  Exp.  Physiology,"  1908,  I,  305. 


456  BLOOD    AND    LYMPH. 

desirable,  of  course,  to  understand  the  process  of  clotting  as  fully 
as  possible.  The  problem  has  proved  to  be  a  difficult  and  com- 
plex one. 

General  Statement  of  Problem. — The  clotting  of  blood  is  such 
a  prominent  phenomenon  that  it  has  attracted  attention  at  all 
times,  and  as  a  result  numerous  theories  to  account  for  it  have  been 
advanced.  Most  of  these  theories  have  now  simply  an  historical 
interest.  In  recent  years  much  experimental  work  has  been  done 
upon  the  subject,  the  result  of  which  has  been  to  increase  greatly 
our  knowledge  of  the  process;  but  no  complete  explanation  has  yet 
been  reached.  It  is  generally  admitted  that  the  essential  constit- 
uent of  the  clot — namely,  the  fibrin — is  formed  from  the  fibrinogen 
normally  present  in  the  plasma,  and  that  without  this  fibrin- 
ogen clotting  is  impossible.  If,  for  instance,  blood  is  heated  to 
60°  C.,  a  temperature  sufficient  to  precipitate  the  fibrinogen  as  a 
heat  coagulum,  its  power  of  clotting  is  lost.  Clotting,  therefore,  is 
essentially  a  process  of  the  blood-plasma,  as  was  shown  indeed  by 
the  old  experimenters  (Hewson).  Moreover,  it  is  also  admitted 
that  the  conversion  of  the  soluble  fibrinogen  to  the  insoluble  fibrin 
is  accomplished  by  the  agency  of  a  substance,  known  as  thrombin 
or  fibrin  ferment,  which  is  not  present,  in  its  active  form  at  least, 
in  the  blood  while  in  the  blood-vessels,  but  is  formed  after  the 
blood  is  shed  or  under  certain  abnormal  conditions  within  the 
blood-vessels.  These  two  important  facts  we  owe  mainly  to 
the  investigations  of  Alexander  Schmidt,*  whose  work  com- 
pleted the  older  observations  of  Hewson,  Buchanan,  Denis, 
and  Briicke. 

Preparation  of  Solutions  of  Fibrinogen. — Fibrinogen  may 
be  obtained  readily  in  solution  free  from  other  proteins  by  the 
general  method  first  described  by  Hammarsten.  One  may  use 
the  plasma  of  horse's  blood  which  has  been  kept  from  clotting 
by  prompt  cooling,  and  in  which  the  corpuscles  have  been  thrown 
down  by  centrifugalizing  or  by  long  standing  at  low  temperature, 
but  it  is  more  convenient,  perhaps,  to  use  blood  which  has  been 
kept  from  clotting  by  allowing  the  blood,  as  it  escapes  from  the 
vessels,  to  run  into  a  solution  of  sodium  oxalate,  using  an  amount 
such  that  the  final  mixture  contains  0.1  per  cent,  of  the  oxalate. 
This  mixture  is  centrifugalized,  the  clear  plasma  is  removed,  and 
the  fibrinogen  in  it  is  precipitated  by  adding  an  equal  part  of  a 
saturated  solution  of  sodium  chlorid. 

The  method  in  some  detail  is  as  follows:  After  adding  to  the  clear  plasma 
an  equal  bulk  of  a  saturated  solution  of  sodium  chlorid  the  resulting  pre- 

*  "Archiv  f.  Anat.,  Physiologic,  u.  wiss.  Medicin,"  Reichert  u.  du  Bois- 
Reymond,  1864,  pp.  545,  675,  and  1862,  pp.  428,  533;  "Pfliiger's  Archiv.  f. 
d.  gesammte  Physiol.,"  6,  413,  1872;  "Zur  Blutlehre/'  Leipzig,  1892  and  1895. 


COAGULATION.  457 

cipitate  of  fibrinogen  is  centrifugalized,  the  supernatant  liquid  is  poured 
off,  the  precipitate  is  washed  with  a  little  of  a  half-saturated  solution  of 
sodium  chlorid,  and  then  dissolved  with  stirring  in  a  2  per  cent,  solution  of 
sodium  chlorid  and  filtered.  This  solution  is  again  precipitated  by  half- 
saturation  with  sodium  chlorid,  centrifugalized,  washed,  and  dissolved 
as  before  in  a  2  per  cent,  solution  of  sodium  chlorid.  The  process  may  be 
repeated  a  third  time,  and  the  washed  precipitate  is  finally  dissolved  in  a 
1  per  cent,  solution  of  sodium  chlorid.  It  frequently  happens  that  the  third 
or  even  the  second  precipitate  will  not  dissolve  in  the  dilute  sodium  chlorid, 
and  in  that  case  a  drop  or  two  of  a  0.5  per  cent,  solution  of  sodium  bicarbonate 
may  be  added  to  carry  it  into  solution.  If  care  is  taken  in  washing  the  centrif- 
ugalized precipitate,  two  precipitations  usually  suffice  to  give  a  fibrinogen 
solution,  which  will  not  clot  spontaneously  nor  after  the  addition  of  calcium 
salts,  but  clots  promptly  with  thrombin. 

A  solution  of  fibrinogen  prepared  as  above  clots  readily  upon 
the  addition  of  blood-serum  or  of  other  solutions  containing 
thrombin,  and  if  the  preparation  has  been  entirely  successful,  a 
genuine  clot,  that  is,  the  precipitation  of  the  fibrinogen  in  gelatin- 
ous form,  cannot  be  obtained  from  it  by  any  other  means.  As  a 
matter  of  fact,  solutions  of  fibrinogen  prepared  as  described  some- 
times clot,  although  much  more  slowly,  when  instead  of  a  throm- 
bin solution  one  adds  a  little  calcium  chlorid  or  a  solution  con- 
taining calcium  chlorid  and  sodium  bicarbonate  in  about  the 
proportion  found  in  a  Ringer's  mixture.  This  latter  fact  indicates 
that  the  fibrinogen  solution  in  such  cases  contains  a  trace  of  some 
material  from  which  thrombin  may  be  produced.  In  all  probability 
this  material  is  the  antecedent  form  of  thrombin,  that  is,  so-called 
prothrombin,  which,  as  we  shall  see,  is  converted  to  thrombin  by 
the  action  of  calcium  salts. 

Preparation  and  Properties  of  Thrombin. — Thrombin,  or  so- 
called  fibrin  ferment,  is  prepared  readily  by  the  method  first  de- 
scribed by  Schmidt.  Blood  is  allowed  to  clot,  and  the  serum  is  then 
precipitated  by  the  addition  of  a  large  excess  of  alcohol  (usually 
twenty  volumes).  After  standing  some  days  or  weeks  the  pre- 
cipitate is  drained  off  and  dried,  and  is  then  ground  up  and  ex- 
tracted with  water.  The  aqueous  extract  contains  proteins, 
salts,  and  other  things  in  addition  to  the  thrombin.  A  solution 
made  in  this  way  causes  a  prompt  coagulation  when  added  to 
a  solution  of  pure  fibrinogen.  That  the  thrombin  thus  obtained 
is  not  present  as  such  in  normal  blood,  but  is  formed  after  shed- 
ding, is  indicated  by  the  fact  that  if  the  animal's  blood  is  allowed 
to  flow  directly  from  the  artery  into  a  large  bulk  of  alcohol,  due 
care  being  taken  in  the  process,  the  precipitate  thus  obtained  when 
subsequently  dried  and  extracted  with  water  yields  little  or  no 
thrombin. 

Another,  perhaps  simpler,  method  of  obtaining  a  strong  prep- 
aration of  thrombin  is  to  treat  fibrin  with  an  8  per  cent,  solution  of 
sodium  chlorid  (Buchanan-Gamgee) .  Fibrin  obtained  from  a 


458  BLOOD    AND    LYMPH. 

slaughter-house  is  washed  thoroughly  in  running  water  until  the 
Hemoglobin  is  removed,  and  is  then  minced  and  extracted  at  a  low 
temperature  with  the  strong  salt  solution  for  several  days.  The 
filtered  extract  is  rich  in  thrombin,  but  contains  also  large  amounts 
of  dissolved  protein.  Starting  with  such  an  extract  the  author* 
has  shown  that  by  repeated  shakings  with  chloroform  the  coagu- 
lable  proteins  present  in  the  extract  may  be  removed  completely 
and  the  thrombin,  in  diminished  quantities,  be  left  behind  in 
apparently  pure  condition. 

A  simpler  method  of  obtaining  relatively  pure  preparations  of  thrombin 
in  permanent  form  for  experimental  work  and  demonstrations  may  be  de- 
scribed briefly  as  follows: 

1.  Fibrin  obtained  from  the  slaughter-house  is  washed  thoroughly  to  re- 
move all  hemoglobin.     The  mass  is  squeezed  to  remove  excess  of  water,  is 
then  cut  into  fine  pieces  with  scissors,  and  covered  with  an  8  per  cent,  solution 
of  sodium  chlorid.     The  mixture  is  left  for  forty-eight  hours  in  a  refrigerator, 
with  occasional  stirring. 

2.  The  salt  solution  is  drained  off  through  cheese-cloth. 

3.  The  filtrate  is  precipitated  by  the  addition  of  an  equal  volume  of  acetone, 
and  this  mixture  is  filtered  as  quickly  as  possible  through  a  number  of  small 
filters,  not  using  more  than  50  c.c.  to  a  filter.      After  the  liquid  has  run  through 
the  filters  are  opened,  and  the  precipitate  is  spread  as  thin  as  possible  with  a 
spatula.     The  niters  are  then  dried  rapidly  in  a  current  of  cold  air  before  an 
electric  fan. 

4.  The  dried  filters  may  be  kept  indefinitely  in  a  desiccator,  and  when 
thrombin  is  needed  may  be  extracted  with  a  little  water,  or  the  thrombin  may 
be  extracted  from  the  whole  mass  by  covering  the  filters  with  water,  al- 
lowing to  stand  for  one  or  two  hours,  and   then  filtering  without  squeezing 
the  filters.     The  clear  solution  of  fibrin  thus  obtained  may  be  distributed  in 
watch  glasses,  1  or  2  c.c.  to  a  glass,  and  be  dried  in  front  of  an  electric  fan. 
These  dried  preparations  may  be  kept  indefinitely  in  a  desiccator.     When 
needed  the  contents  of  each  glass  are  dissolved  in  2  or  3  c.c.  of  water  or  normal 
saline.     This  preparation  contains  a  little  coagulable  protein  in  addition  to 
thrombin.     If  desired  this  impurity  may  be  removed  by  dialyzing  and  shaking 
with  chloroform,  or  by  reprecipitation  with  acetone. 

Observations  made  upon  preparations  of  thrombin  purified 
as  just  described  show  that  it  has  the  following  properties:  it  is 
very  easily  soluble  in  water,  it  is  not  coagulated  by  boiling,  it  is 
precipitated  with  difficulty  by  alcohol  in  excess,  it  is  precipitated 
uninjured  by  half-saturation  with  ammonium  sulphate,  it  responds 
to  a  number  of  the  ordinary  protein  tests,  such  as  the  biuret,  the 
Millon's,  and  especially  the  tryptophan  (Adamkiewicz)  reaction. 
We  may  conclude,  therefore,  that  in  all  probability  thrombin  is  a 
protein  substance.  The  evidence  at  hand  indicates  that  thrombin 
as  such  does  not  exist  in  the  circulating  blood,  but  is  present  prob- 
ably in  an  antecedent  or  inactive  form  known  as  prothrombin  or 
thrombogen.  So  far  as  is  known  this  prothrombin  is  furnished  only 
by  the  blood-platelets,  the  bone-marrow,  f  and  possibly  the  lymph- 

*  Howell,  "American  Journal  of  Physiology,"  26,  453,  1910. 

t  C.  K.  and  K.  R.  Drinker,  "American  Journal  of  Physiology,"  41, 5, 1916. 


COAGULATION.  459 

glands.  When  the  blood  is  shed,  or  under  certain  abnormal  condi- 
tions while  circulating  in  the  vessels,  the  prothrombin  is  changed 
or  activated  to  thrombin.  The  nature  of  this  change  is  discussed 
below.  Once  the  thrombin  exists  in  active  condition  it  exhibits 
the  remarkable  property  of  precipitating  the  fibrinogen  in  the  form 
of  a  gelatinous  clot,  the  essential  part  of  the  clot  being  a  mesh  of 
fibrin  needles. 

Nature  of  the  Action  of  the  Thrombin  on  Fibrinogen. — Solu- 
tions of  fibrinogen  may  be  precipitated  readily  in  a  number  of  ways, 
but,  so  far  as  known,  only 'thrombin  is  capable  of  precipitating  it 
in  the  peculiar  way  necessary  to  form  a  gelatinous  clot.  The 
nature  of  this  reaction  is  obscure.  The  usual  view  in  physiology 
is  that  first  suggested  by  Schmidt,  namely,  that  the  thrombin  is 
an  enzyme  or  ferment,  fibrin  ferment.  If  this  view  is  correct,  then, 
in  accordance  with  our  idea  of  the  way  in  which  ferments  act,  the 
thrombin  should  not  be  used  up  in  the  reaction,  but  should  act 
over  and  over  again,  converting  new  fibrinogen  to  fibrin.  Moreover, 
the  fibrin  on  this  view  should  be  formed  entirely  from  the  fibrinogen, 
since  the  thrombin,  if  a  ferment,  does  not  constitute  a  part  of  the 
final  product.  Several  specific  hypotheses  have  been  proposed  to 
explain  the  nature  of  the  change  undergone  by  the  fibrinogen 
in  its  conversion  to  fibrin.  It  has  been  suggested  that  the  fibrino- 
gen undergoes  a  hydrolytic  cleavage,  with  the  formation  of  the 
insoluble  fibrin,  on  the  one  hand,  and  a  soluble  "  fibrin  globulin," 
on  the  other;  or  that  the  molecular  state  of  the  fibrinogen  undergoes 
a  change  similar  perhaps  to  that  caused  by  heating,  whereby  an 
insoluble  product  is  formed.  These  and  similar  hypotheses  have 
not  been  supported  by  experimental  evidence,  and,  indeed,  a  number 
of  observers  from  time  to  time  have  questioned  the  fundamental 
part  of  such  theories,  namely,  the  belief  that  thrombin  acts  like  a 
ferment.  Experiments  indicate  that,  unlike  the  ferments  in  general, 
thrombin  under  certain  conditions  (absence  of  salts)  withstands 
the  temperature  of  boiling  water,  and,  again,  unlike  the  ferments, 
a  small  amount  of  thrombin  allowed  to  act  upon  fibrinogen  pro- 
duces a  fixed  amount  of  fibrin  which  does  not  increase  with  the 
time  during  which  the  thrombin  is  allowed  to  act.  It  has  been 
suggested,  therefore,  as  an  alternative  hypothesis  that  the  throm- 
bin and  fibrinogen  form  a  combination  of  a  physical  or  physico- 
chemical  character  which  results  in  their  mutual  precipitation  as 
fibrin  (Nolf ) .  Such  a  theory  is  in  accord  with  the  fact  that  freshly 
formed  fibrin  when  subjected  to  prolonged  washing  with  water 
gives  off  little  or  no  thrombin,  but  when  subsequently  treated  with 
solutions  of  sodium  chlorid  (8  per  cent.)  a  portion  of  it  goes  into 
solution  and  this  solution  is  rich  in  thrombin. 

The  Influence  of  Calcium  Salts  in  Coagulation. — Many  ob- 


460  BLOOD    AND    LYMPH. 

servers  have  called  attention  to  the  fact  that  calcium  salts  in  cer- 
tain concentrations  influence  favorably  the  coagulation  of  blood. 
We  owe  to  Arthus  and  Pages,  however,  the  proof  that  calcium 
salts  are  essential  to  the  process  of  normal  coagulation.  These 
observers  showed  that  freshly  drawn  blood  allowed  to  flow  into 
an  oxalate  solution,  in  amounts  such  that  the  final  concentration 
in  oxalate  is  not  less  than  0.1  per  cent.,  will  remain  unclotted  in- 
definitely, but  may  be  made  to  clot  at  any  time  by  the  addition 
of  a  suitable  amount  of  calcium  salt.  Much  discussion  has  ensued 
in  regard  to  the  precise  role  played  by  calcium  in  the  process  of 
clotting.  The  outcome  of  this  work  justifies  the  statement  that 
calcium  is  not  concerned  in  the  final  stage  of  clotting;  namely,  the 
reaction  between  fibrinogen  and  thrombin,  but  takes  an  essential 
part  in  the  first  stage,  the  conversion  of  prothrombin  to  thrombin. 
According  to  the  terminology  used  at  present,  we  may  say  that 
calcium  is  necessary  for  the  activation  of  the  thrombin.  In  the 
oxalated  plasma  fibrinogen  and  prothrombin  or  inactive  thrombin 
are  present,  and  the  addition  of  calcium  salts  serves  simply  to  con- 
vert the  prothrombin  to  thrombin.  If  fully  formed  thrombin 
prepared  by  any  of  the  methods  described  is  added  to  oxalated 
plasma  clotting  occurs,  although  no  calcium  is  present. 

Influence  of  Tissue  Extracts  Upon  Coagulation. — Another  im- 
portant consideration  in  the  normal  clotting  of  blood  is  the  in- 
fluence of  extracts  of  tissues  upon  the  rapidity  of  the  process. 
Many  observers  have  shown  that  certain  substances  are  contained 
in  the  tissues  in  general,  including  the  blood-corpuscles,  which 
tend  to  accelerate  the  process  of  clotting.  Arthus,  for  example, 
found  that  blood  taken  directly  from  the  artery  of  a  mammal 
through  a  clean  tube  will  clot  within  a  certain  time,  while  if  allowed 
to  flow  first  over  the  wounded  surface,  as  happens  under  normal 
conditions,  the  time  of  clotting  is  much  accelerated.  This  in- 
fluence of  the  tissues  is  shown  in  an  extreme  way  when  we  consider 
the  blood  of  the  lower  vertebrates,  the  birds,  reptiles,  and  fishes. 
If  blood  is  drawn  from  an  artery  of  one  of  these  animals  through 
a  clean  tube  it  clots  with  great  slowness.  If  such  a  specimen  of 
blood  is  centrifugalized  promptly  the  supernatant  plasma,  when 
pipetted  off,  may  remain  unclotted  for  many  hours  or  fail  to  clot 
at  all.  If,  however,  the  drawn  blood  or  the  centrifugalized  plasma 
is  mixed  with  an  extract  from  the  animaPs  tissues,  the  muscles, 
for  example,  it  will  clot  within  a  few  minutes.  This  is,  of  course, 
what  happens  in  such  animals  when  wounded.  The  escaping 
blood  oozes  over  the  cut  surface  and  clotting  occurs  promptly. 
Mammalian  blood  differs  from  that  of  the  lower  vertebrates  in 
that  it  clots  within  a  relatively  short  time,  even  if  kept  from  coming 
in  contact  with  the  injured  tissues,  and  this  difference  may  be  ex- 


COAGULATION.  461 

plained  on  the  view  that  the  accelerating  substance  furnished 
by  the  tissues  in  the  lower  vertebrates  is  supplied  in  the  case 
of  the  mammal  by  the  corpuscles  in  its  own  blood,  most  prob- 
ably by  the  platelets  which,  as  is  well  known,  disintegrate  very 
rapidly  when  the  blood  is  shed.  The  mammalian  blood  (dog) 
may,  however,  be  brought  into  the  condition  of  the  bird's  blood 
very  easily  by  the  so-called  process  of  peptonization,  that  is 
to  say,  by  injecting  rapidly  into  the  circulation  a  certain  amount 
of  a  solution  of  Witte's  peptone  (see  below,  Antithrombin) .  If 
the  injection  is  successful,  <the  blood  when  drawn  remains  fluid 
for  many  hours,  and,  if  promptly  centrifugalized,  the  plasma  may 
fail  entirely  to  clot.  In  such  cases  the  addition  of  tissue  extracts 
may  cause  clotting  within  a  few  minutes,  as  in  the  case  of  the  bird's 
blood.  The  substance  or  substances  in  the  tissues  which  exhibit 
this  accelerating  influence  upon  clotting  have  received  various  names 
from  different  observers  in  accordance  with  the  special  theory  of 
coagulation  advocated.  They  have  been  called  zymoplastic  sub- 
stances, thromboplastic  substances,  coagulins,  cytozyms,  thrombo- 
kinase,  etc.  It  is  perhaps  most  convenient  to  speak  of  them  in 
general  as  thromboplastic  substances,  since  this  term  does  not  com- 
mit us  to  the  manner  of  their  action,  but  simply  implies  that  they 
are  of  importance  in  the  formation  of  the  clot.  It  has  long  been 
known  that  thromboplastic  substance  may  be  extracted  from  the 
tissues  by  the  action  of  ether,  or  of  alcohol  and  ether,  and  the 
author*  has  shown  that  the  active  substance  in  the  ether  extracts 
is  one  of  the  phosphatids,  corresponding  apparently  to  the  sub- 
stance which  has  been  designated  as  cephalin.  The  closely  related 
lecithin  has  no  thromboplastic  power.  In  aqueous  extracts  of  the 
tissues  the  cephalin  is  held  in  solution  in  combination  with  a  pro- 
tein which  is  precipitated  at  a  temperature  of  60°  C.  It  is  probable 
that  this  cephalin-protein  constitutes  the  active  thromboplastic 
substance  of  the  tissues.  As  regards  the  manner  in  which  it  par- 
ticipates in  the  process  of  clotting  several  views  have  been  pro- 
posed. Two  of  these  views  are  referred  to  in  some  detail  in  the 
next  paragraph. 

Theory  of  Coagulation. — Modern  theories  of  coagulation,  with 
some  exceptions  (Wooldridge,  Nolf),  accept  as  their  starting-point 
the  fact  that  fibrin  is  formed  eventually  by  the  action  of  thrombin 
upon  fibrinogen.  The  various  theories  proposed  differ  from  one 
another  largely  in  their  explanation  of  the  origin  of  the  thrombin 
and  of  the  parts  taken  by  the  calcium  and  the  thromboplastic 
substances  in  the  process  of  clotting.  The  simplest  of  these 
theories  assumes  that  the  prothrombin  in  the  blood  arises  from  the 
blood-plates  (and  leucocytes  ?)  and  is  activated  to  thrombin  by 
*  Howell,  "American  Journal  of  Physiology,"  31, 1, 1912,  and  32,  264, 1913. 


462  BLOOD    AND    LYMPH. 

the  calcium,  the  thrombin  then  reacting  with  the  fibrinogen.  The 
theory  which  seems  to  be  most  generally  accepted  at  present  is 
that  proposed  independently  by  Morawitz*  and  by  Fuld  and  Spiro  f 
Using  the  terminology  of  Morawitz,  this  theory  assumes  that  the 
thrombin  is  present  in  the  blood  in  an  inactive  form  which  he 
designates  as  thrombogen.  To  convert  this  thrombogen  (pro- 
thrombin)  to  thrombin  requires  the  action  both  of  calcium  salts 
and  of  an  organic  thromboplastic  substance  which  he  designates 
as  a  kinase  or  thrombokinase.  Thrombokinase  is  furnished  by  the 
tissue-cells  in  general,  especially  by  those  rich  in  nuclein,  and  is 
furnished  also  by  the  cellular  elements  of  the  blood.  In  the  cir- 
culating blood  calcium  salts  and  thrombogen  are  present,  but  no 
kinase.  When  the  blood  is  shed  the  disintegration  of  the  platelets 
and  leucocytes,  in  mammalian  blood,  or  of  the  cells  of  the  wounded 
tissues  in  the  blood  of  the  lower  vertebrates,  liberates  thrombo- 
kinase, which  then,  in  combination  with  the  calcium,  converts  the 
thrombogen  to  thrombin.  The  theory  may  be  expressed  in  dia- 
grammatic form  as  follows: 

Cellular  elements  — — *•  thrombokinase 

Thrombokinase  +  calcium  -f  thrombogen  =  thrombin 

Thrombin  +  fibrinogen  =  fibrin. 

Morawitz  has  made  no  suggestion  in  regard  to  the  chemical 
nature  of  thrombokinase,  but  under  this  term  he  refers  to  the 
active  substance  in  tissue  extracts,  which  has  been  explained  in  the 
preceding  paragraph  as  cephalin  or  a  cephalin-protein  compound. 

The  theory  explains  very  well  many  of  the  most  significant 
facts  known  in  regard  to  clotting,  but  it  may  be  said  that  the  cen- 
tral feature  of  the  theory,  the  existence  of  an  organic  kinase,  has 
not  been  supported  by  direct  experimental  evidence.  The  author 
has  been  led  by  his  own  work  J  to  adopt  a  different  point  of  view, 
which  may  be  expressed  briefly,  as  follows:  Prothrombin  may  be 
converted  to  active  thrombin  by  the  action  of  calcium  alone. 
This  activation  does  not  occur  in  the  circulating  blood  because  an 
inhibitory  substance  (antithrombin)  is  present  in  amounts  sufficient 
to  prevent  the  reaction.  In  shed  blood  the  tissue-cells  or  the  cells 
of  the  blood  (plates)  furnish  a  thromboplastic  substance  (cephalin- 
protein)  which  neutralizes  the  action  of  the  antithrombin  and  thus 
permits  the  calcium  to  react  with  the  prothrombin  to  form  throm- 
bin, which  in  turn  reacts  with  the  fibrinogen  to  form  fibrin.  Both 
theories  assume  that  the  process  of  clotting  in  shed  blood  is 

*  Morawitz,  Hofmeister's  "Beitrage,"  5,  133,  1904,  and  "Arch.  f.  klin. 
Med.,"  79,  1. 

t  Fuld  and  Spiro,  "Hofmeister's  Beitrage,"  5,  174,  1904. 

j  Howell,  loc.  tit.  and  "American  Journal  of  Physiology,"  29, 187,  1911. 


COAGULATION.  463 

initiated  by  the  production  of  a  new  substance,  the  thromboplastic 
substance,  furnished  by  the  cells  or  blood-corpuscles  (plates), 
but  on  one  view  this  substance  acts  as  a  kinase  which  participates 
directly  in  the  conversion  of  prothrombin  to  thrombin,  while  on 
the  other  view  the  substance  permits  this  conversion  to  occur 
indirectly  by  neutralizing  the  opposing  antithrombin. 

Several  other  theories  of  coagulation  are  proposed,  but  they  are  difficult 
to  explain  in  a  few  words.  Two  of  the  most  recent  of  these  theories  may  be 
referred  to  briefly.  According  to  Nolf*  the  essential  factors  of  coagulation 
are  three  colloids,  fibrinogen  an/i  thrombogen  furnished  by  the  liver  and 
thrombozym  derived  from  the  leucocytes.  These  colloids  unite  to  form  fibrin, 
but  in  order  for  the  reaction  to  take  place  calcium  must  be  present,  as  also 
thromboplastic  substance.  Bordet  and  Delangef  explain  the  formation  of 
thrombin  as  due  to  a  reaction  between  substances  designated  as  cytozym  and 
serozym.  The  cytozym  is  furnished  by  the  platelets  (and  tissues).  It  is  not 
destroyed  by  boiling.  The  serozym  is  a  substance  not  present  in  blood,  but 
formed  in  some  way  after  the  blood  is  shed.  It  is  destroyed  by  heating  to 
55°  C.  The  reaction  between  cytozym  and  serozym  requires  the  presence  of 
calcium  salts. 

Why  Blood  Does  Not  Clot  Within  the  Blood-vessels.— Anti- 
thrombin.— The  specific  explanation  of  the  fluidity  of  the  blood 
within  the  vessels  must  vary,  of  course,  with  the  theory  of  coagula- 
tion that  is  adopted.  In  general,  it  may  be  stated  with  confidence 
that  the  circulating  blood  contains  no  active  thrombin,  or  at  least 
not  enough  to  clot  the  blood,  and  the  real  difficulty  we  have  to  ex- 
plain is  how  the  prothrombin  is  kept  in  an  inactive  state  through- 
out life.  According  to  Morawitz,  everything  turns  on  the  fact 
that  thrombokinase  is  absent.  The  fibrinogen,  prothrombin,  and 
calcium  are  in  solution  in  the  blood-plasma,  but  according  to  his 
theory  the  kinase  is  essential  to  aid  the  calcium  in  activating  the 
prothrombin.  Cellular  elements,  platelets,  leucocytes,  erythro- 
cytes  doubtless  are  constantly  undergoing  disintegration  in  the 
circulation  and  thereby  furnish  some  kinase,  but  under  normal 
conditions  this  does  not  occur  in  mass,  as  is  the  case  in  shed  blood. 
The  explanation  is  logically  satisfactory,  if  we  accept  the  theory  of 
a  kinase,  although  it  does  not  accord  very  well  with  the  fact  that 
large  amounts  of  tissue  extracts,  containing  the  kinase,  may  be 
injected  into  the  circulation  without  producing  intravascu'ar 
clotting.  Another  point  of  view  is  that  the  normal  fluidity  of  the 
blood  is  maintained  by  the  constant  presence  of  an  inhibiting  sub- 
stance. Substances  of  this  kind  are  known.  The  one  that  is  most 
familiar  is  hirudin,  a  protein  body  prepared  from  the  salivary  gland 
of  the  leech  (Hirudo  medicinalis).  Hirudin  is  readily  soluble  in 
water  and  has  the  property  of  preventing  the  action  of  thrombin 
upon  fibrinogen.  It  may  be  designated  properly,  therefore,  as  an 
antithrombin.  It  is  much  used  in  experimental  work  when  it  is 

*  "Archives  internationales  de  physiol.,"  6,  115,  1908. 
t  "Annales  de  Tinstitut  Pasteur,"~26,  657  and  737,  1912. 


464  BLOOD    AND    LYMPH. 

desired  to  render  the  blood  of  an  animal  incoagulable.  A  substance 
having  a  similar  action  exists  in  blood.  Its  chemical  nature  is  not 
known,  so  that  it  must  be  designated  by  the  general  term  "anti- 
thrombin." The  quantity  present  in  any  given  specimen  of  blood 
may  be  estimated  with  some  degree  of  exactness  by  ascertaining  the 
extent  of  its  retarding  or  inhibitory  power  when  a  definite  amount 
of  plasma  is  added  to  a  known  mixture  of  thrombin  and  fibrinogen. 
Experiments  of  this  kind  have  shown  that  in  the  blood  of  birds  and 
reptiles  which  clots  slowly  (provided  it  does  not  come  into  contact 
with  the  tissues)  more  antithrombin  is  present  than  in  the  blood  of 
the  mammal.  In  dog's  blood  the  normal  amount  of  antithrombin 
may  be  increased  greatly  by  the  process  of  peptonization.  This 
process  consists  in  injecting  into  the  circulation  a  strong  solution  of 
Witte's  peptone  in  amounts  equal  to  0.3  to  0.4  gram  per  kilogram  of 
animal.  The  result  of  the  injection  is  to  render  the  dog's  blood  in- 
coagulable for  a  time,  and  this  effect  seems  to  be  explained  by  the 
large  increase  in  antithrombin.  Peptonized  blood  may  be  made  to 
clot  by  the  addition  of  a  solution  of  cephalin  or  of  the  extract  of  a 
tissue.  It  has  been  suggested  that  the  normal  fluidity  of  the  cir- 
culating blood  is  dependent  in  the  first  instance  upon  the  protecting 
influence  of  the  antithrombin,  and  that  when  the  blood  is  shed  the 
antithrombin  is  neutralized  by  the  thromboplastic  substance 
(cephalin)  liberated  by  the  disintegration  of  the  platelets  or  fur- 
nished by  the  surrounding  wounded  tissue.  The  whole  matter  of 
the  cause  of  the  normal  fluidity  of  the  blood  is  complicated  some- 
what by  the  discovery  that  other  substances  are  formed  in  the 
body  (liver,  heart,  etc.)  which  retard  or  prevent  coagulation  not, 
as  in  the  case  of  antithrombin,  by  preventing  a  reaction  between 
thrombin  and  fibrinogen,  but  by  opposing  the  activation  of  pro- 
thrombin  to  thrombin.*  In  other  words,  we  have  to  recognize  the 
existence  of  an  antiprothrombin  as  well  as  an  antithrombin.  The 
latter  is  known  to  occur  normally  in  the  blood,  but  whether  the 
former  is  also  present  in  blood  has  not  been  determined.  The  sub- 
stance which  has  an  antiprothrombin  action  belongs  chemically  to 
the  phosphatids,  but  the  chemical  nature  of  the  antithrombin  is 
unknown.  Doyon  f  believes  that  it  is  a  nucleic  acid  compound,  but 
this  view  is  not  in  accord  with  the  facts  known  in  regard  to  the  anti- 
thrombin of  blood.  Delezenne,  Wolf,  and  others  t  have  published 
experiments  which  indicate  that  the  blood  antithrombin  is  formed 
in  the  liver. 

Metathrombin. — In  the  serum  of  blood  after  clotting  ready- 
formed  thrombin  exists.    On  standing  the  amount  of  this  thrombin 

*  Howell,  "Harvey  Lectures,"  1916-17. 

t  Doyon,  "Comptes.  rend,  de  la  Soc.  de  Biologic,"  1911-13. 

j  Denny  and  Minot,  "American  Journal  of  Physiology,"  38,  233,  1915. 


COAGULATION.  465 

diminishes  sometimes  quite  rapidly,  so  that  after  a  certain  time  the 
serum  shows  little  or  no  power  to  cause  the  clotting  of  a  fibrinogen 
solution.  In  either  a  fresh  or  an  old  serum,  if  not  kept  too  long, 
the  thrombic  power  can  be  very  greatly  increased  if  it  is  treated 
with  an  equal  volume  of  a  decinormal  solution  of  sodium  hy- 
droxid  for  a  few  minutes  and  then  neutralized  with  acid  (Fuld  and 
Spiro  and  Morawitz).  When  this  same  method  of  alkali-acid 
treatment  is  applied  to  plasma  (oxalated  plasma)  no  yield  of  throm- 
bin  is  obtained.  It  is  evident  from  these  facts  that  serum  contains 
a  source  of  thrombin  other  than  prothrombin,  which  does  not  exist 
in  plasma.  Morawitz  designated  this  form  of  inactive  thrombin  as 
metathrombin.  Several  observers*  in  this  country  have  given  rea- 
sons for  believing  that  metathrombin  is  a  compound  of  thrombin 
and  antithrombin.  It  is  known  that  serum  has  a  large  capacity 
for  inactivating  thrombin.  When  the  latter  is  added  to  serum  it 
soon  disappears,  and  the  suggestion  made  is  that  it  combines  with 
antithrombin  to  form  metathrombin.  On  this  view  it  would  seem 
that  in  fresh  serum  there  is  present  some  active  thrombin  left  over 
from  the  coagulation,  and  two  forms  of  inactive  thrombin;  namely, 
some  prothrombin  not  converted  to  thrombin  in  the  act  of  clotting, 
and  some  metathrombin  formed  after  the  act  of  clotting  by  a  union 
of  free  thrombin  and  antithrombin.  The  prothrombin  of  serum 
may  be  converted  to  thrombin  by  adding  cephalin  or  tissue-extract, 
but  to  liberate  thrombin  from  metathrombin  requires  the  stronger 
alkali-acid  treatment  described  above.  It  has  been  suggested 
(Gasser)  that  the  formation  of  metathrombin  constitutes  normally 
a  safety  device  to  prevent  intra vascular  clotting;  that  is  to  say,  if 
thrombin  is  formed  in  small  quantities  in  the  circulating  blood  it 
may  be  seized  and  inactivated  by  the  antithrombin.  Under  the 
conditions  of  shed  blood  when  there  is  a  more  massive  production  of 
thrombin  this  protection  is  inadequate.  Clotting  takes  place,  but 
the  excess  of  thrombin  left  over  is  soon  inactivated  by  conversion 
to  metathrombin. 

Intravascular  Clotting. — As  is  well  known,  clots  may  form 
within  the  blood-vessels  in  consequence  of  the  introduction  of  for- 
eign material  of  any  kind.  Air,  for  instance,  that  has  gotten  into 
the  veins,  if  not  absorbed,  may  act  as  a  foreign  substance  and 
cause  the  same  chain  of  events  as  when  the  blood  is  shed, — namely, 
the  disintegration  of  formed  elements,  formation  of  thrombin,  and 
clotting.  So  also  when  the  internal  coat  of  a  blood-vessel  is  in- 
jured, as,  for  instance,  by  a  ligature,  the  altered  endothelial  cells 
act  as  a  foreign  substance.  If  the  circulatory  conditions  are  favor- 
able— for  instance,  if  the  ligated  artery  causes  a  stasis  of  blood  at 

*Weymouth,  "American  Journal  of  Physiology,"  32,  266,  1913;  Gasser, 
ibid.,  42,  378,  1917;  and  Rich,  ibid.,  43,  549,  1917. 

30 


466  BLOOD    AND    LYMPH. 

that  point — there  may  be  an  agglutination  of  the  blood  plates, 
starting  at  the  injured  surface,  and  the  subsequent  formation  of  a 
clot.  Intravascular  clotting  may  also  be  produced  by  the  injection 
of  various  substances.  From  our  knowledge  of  the  factors  con- 
cerned in  coagulation  we  should  suppose  that  the  normal  balance 
of  the  blood  might  be  overthrown  in  one  of  two  general  ways, 
by  injecting  active  thrombin  or  by  injecting  extracts  of  the  tissues 
(thromboplastic  substance).  As  a  matter  of  fact,  intravascular 
clotting  may  be  produced  by  either  of  these  methods,  but  experi- 
ments have  developed  the  somewhat  unexpected  result  that  the 
blood  or  the  body  can  protect  itself  within  wide  limits  from  the 
effects  of  such  injections.  Solutions  of  pure  thrombin,  or  serum 
or  defibrinated  blood  containing  active  thrombin,  may  be  intro- 
duced into  the  circulation  in  quantities  that  outside  would  suffice 
to  clot  the  whole  mass,  and  yet  no  harm  be  done.  The  explana- 
tion of  this  negative  result,  according  to  the  author's  experiments, 
is  that  the  excess  of  thrombin  within  the  living  animal  causes  the 
formation  of  a  compensatory  amount  of  antithrombin,  probably 
by  a  protective  reflex  secretion.  Tissue  extracts  or  solutions  of 
the  precipitated  thromboplastic  substance  (Wooldridge)  cause 
clotting  more  readily,  but  here  again  injections  of  this  kind,  instead 
of  hastening  the  clotting  of  blood,  may  at  times  have  just  the 
opposite  effect,  giving  what  older  observers  called  the  "negative 
phase  of  the  injection."  On  the  other  hand,  when  the  coagulability 
of  the  blood  is  diminished  experimentally  by  injecting  antithrom- 
bin (hirudin)  directly,  or  by  causing  the  body  to  produce  an  excess 
of  antithrombin  within  itself  (injection  of  Witte's  peptone)  the 
effect  soon  passes  off;  the  excess  of  antithrombin  is  removed  by 
some  procedure  which  is  not  yet  understood.  It  may  be  pointed 
out  that  these  attempts  to  devise  methods  by  means  of  which  the 
coagulability  of  the  blood  may  be  controlled  have  a  practical 
bearing  in  their  application  to  pathological  conditions  in  which 
the  balance  is  already  disturbed  in  the  direction  of  an  increased 
or  decreased  coagulability. 

Means  of  Hastening  or  of  Retarding  Coagulation. — Blood 
coagulates  normally  within  a  few  minutes,  but  the  process  may  be 
hastened  by  increasing  the  extent  of  foreign  surface  with  which  it 
comes  in  contact.  Thus,  agitating  the  liquid  when  in  quantity,  or 
the  application  of  a  sponge  or  a  handkerchief  to  a  wound,  hastens 
the  onset  of  clotting.  This  is  easily  understood  when  it  is  remem- 
bered that  the  breaking  down  of  leucocytes  and  blood-plates  is 
hastened  by  contact  with  foreign  surfaces.  It  has  been  proposed 
also  to  hasten  clotting  in  case  of  hemorrhage  by  the  use  of  throm- 
bin solutions  or  of  tissue  extracts  containing  some  thromboplastic 
substance.  Hot  sponges  or  cloths  applied  to  a  wound  hasten 


COAGULATION.  467 

clotting,  probably  by  accelerating  the  formation  of  thrombin  and 
the  chemical  changes  of  clotting.  Coagulation  may  be  retarded 
or  be  prevented  altogether  by  a  variety  of  means,  of  which  the 
following  are  the  most  important: 

1.  By  Cooling. — This  method  succeeds  well    only  in  blood 
that  clots  slowly — for  example,  the  blood  of  the  horse,  bird,  or 
terrapin.     Blood  from  these  animals  received  into  narrow  vessels 
surrounded  by  crushed  ice  may  be  kept  fluid  for  an  indefinite 
time.     The  blood  corpuscles  soon  sink,  so  that  by  this  means 
one  may  readily  obtain  pure  blood-plasma.     The  cooling  probably 
prevents  clotting  by  keeping  the  corpuscles  intact. 

2.  By  the  Use  of  Oiled  or  Paraffined  Vessels. — If  blood,  when 
withdrawn  from  the  vessels,  is  allowed  to  come  into  contact  only 
with  oiled  or  paraffined  surfaces  its  clotting  is  very  much  delayed. 
Under   ordinary    conditions    blood    brought    into    contact   with 
foreign  surfaces  clots  rapidly,  because  the  platelets  quickly  agglu- 
tinate and  dissolve,  yielding  to  the  plasma  a  supply  of  prothrom- 
bin  and  thromboplastic  substance.     An  oiled  or  paraffined  surface 
is  one  which  the  liquid  of  the  blood  cannot  wet,  and  under  these 
conditions  the  platelets  do  not  undergo  the  rapid   change  in 
surface  properties  that  causes  them  to  break  down.     The  cannula 
used  for  drawing  the  blood  and  the  vessel  for  receiving  it  may  be 
paraffined  conveniently  by  filling  with  a  dilute  solution  of  paraffin 
in  ether,  then  pouring  off  the  solution  and  allowing  to  dry  for  a 
few  minutes.     In  this  way  the  glass  surface  is  coated  with  a  thin, 
uniform  layer  of  paraffin. 

3.  By  the  Action  of  Neutral  Salts. — Blood  received  at  once 
from  the  blood-vessels  into  a  solution  of  such  neutral  salts  as 
sodium  sulphate  or  magnesium  sulphate,  and  well  mixed,  does 
not  clot.     In  this  case  also  the  corpuscles  settle  slowly,  or  they 
may  be  centrifugalized,  and  specimens  of  plasma  be  obtained. 
For  this  purpose  horses'  or  cats'  blood  is  to  be  preferred.     Such 
plasma  is  known  as  " salted  plasma";  it  is  frequently  used  in 
experiments  in  coagulation — for  example,  in  testing  the  efficacy 
of  a  given  thrombin  solution.     The  best  salt  to  use  is  magnesium 
sulphate  in  solutions  of  27  per  cent.:  1  part  by  volume  of  this 
solution  is  usually  mixed  with  4  parts  of  blood;  if  cats'  blood  is 
used,  a  smaller  amount  may  be  taken — 1  part  of  the  solution  to 
9  of  blood.     Salted  plasma   or   salted  blood   again  clots  when 
diluted  sufficiently  with  water  or  when  thrombin  solutions  are 
added  to  it.     Sinc.e  the  action  of  thrombin  on  fibrinogen  is  not 
prevented  by  neutral   salts  in  these  concentrations,  while  an  oxa- 
lated  plasma  which  clots  readily  on  the  addition  of  calcium  is 
prevented  from  so   clotting  when  sodium  chlorid  or  magnesium 
sulphate  is  added  previously  to  a  concentration  of  4  or  5  per  cent., 


468  BLOOD    AND    LYMPH. 

it  follows  that  in  all  probability  the  neutral  salts  exert  a  restraining 
effect  on  the  process  of  clotting  because  they  prevent  or  retard  the 
activation  of  the  prothrombin  by  the  calcium. 

4.  By  the  Action  of  Oxalate  Solutions. — If  blood  as  it  flows  from 
the  vessels  is  mixed  with  solutions  of  potassium  or  sodium  oxalate 
in  proportion  sufficient  to  make  a  total  strength  of  0.1  per  cent, 
or  more  of  these  salts,  coagulation  is  prevented  entirely.    Addi- 
tion of  an  excess  of  water  does  not  produce  clotting  in  this  case, 
but  solutions  of  any  soluble  calcium  salt  quickly  start  the  process. 
The  explanation  of  the  action  of  the  oxalate  solutions  is  simple; 
they  are  supposed  to  precipitate  the  calcium  as  insoluble  calcium 
oxalate. 

5.  By  the  Action  of  Sodium  Fluorid  and  Sodium  Citrate. — Blood 
drawn  directly  into  a  solution  of  sodium  fluorid  does  not  clot.     It  is 
best  to  use  a  3  per  cent,  solution  of  the  fluorid,  and  to  take  1  part 
of  the  solution  to  9  parts  of  blood.     Addition  of  thrombin  to  this 
fluorid  blood  causes  clotting,  while  calcium  salts  are  usually  stated 
to  be  without  effect.     As  a  matter  of  fact,  calcium  salts  cause  a 
precipitate  of  a  portion  of  the  protein,  but  if  added  cautiously  in 
excess  they  induce  clotting,  as  in  the  case  of  the  oxalated  blood. 
The  fluorid  plasma  may  be  made  to  clot  also  by  dialysis.     We 
may  believe  that  the  fluorid,  like  the  oxalate,  prevents  clotting 
by  removing  the  calcium.     The  calcium  is  not  precipitated,  but  is 
held  bound  as  a  fluorid  in  combination  with  a  portion  of  the 
protein  (Rettger).     Coagulation  is  prevented  in  a  similar  way  by 
solutions  of  sodium  citrate.     In  the  case  of  the  citrate  one  uses  a  2 
per  cent,  solution  and  takes  1  part  to  4  of  the  blood.     As  in  the  case 
of  the  fluorid,  the  citrate  solutions  do  not  cause  an  actual  precipitate 
of  calcium.     One  explanation  given  for  their  efficiency  in  prevent- 
ing clotting  is  that  the  calcium  salt  formed  has  a  very  small  dis- 
sociation constant,  .so  that  the  concentration  of  calcium  ions  is 
reduced  below  the  minimum  necessary  to  activate  prothrombin  to 
thrombin.* 

6.  By  the  Injection  of  Certain  Organic  Substances. — There  are  a 
number  of  substances  which  when  injected  into  the  blood  retard 
or  prevent  its   coagulation.     For   instance,  solutions  of  ordinary 
preparations   of   pepsin,    trypsin,    peptone,    snake    venom,   leech 
extracts,  etc.     Snake  venom  may  be  wonderfully  potent  in  this 
particular;  it  is  stated  that  so  little  as  0.00001  gm.  to  each  kilogram 
of  animal  suffices,  to  destroy  the  coagulability  of  the  blood.     Of 
these  various  bodies  solutions  of  peptone  have  received  the  most 
attention  from  investigators.     Peptone,  as  usually  obtained  by 
digestion   experiments,   is  in   reality   a  mixture  of  proposes  and 
peptones.     When  injected  into  the  circulation  in  the  proportion  of 

*  Sabbatani,  "Archives  ital.  de  Biologie,"  39,  333,  1903. 


COAGULATION.  469 

0.3  gm.  to  each  kilogram  of  animal  the  coagulability  of  the  blood  is 
very  greatly  diminished  for  a  brief  period  of  half  an  hour  or  more. 
When,  however,  such  solutions  are  added  to  freshly  drawn  blood 
they  exercise  no  influence  upon  the  coagulation.  Evidently, 
therefore,  when  injected  into  the  blood  they  provoke  a  reaction  of 
some  sort,  the  products  of  which  prevent  coagulation.  There  is 
evidence  to  show  that  this  reaction  takes  place  in  the  liver,  and  in 
accordance  with  this  view  it  is  found  that  much  smaller  quantities 
of  the  peptone  solution  suffice  to  give  a  delayed  coagulation  when 
injected  directly  into  the ,.  portal  vein.  As  stated  in  the  pre- 
ceding paragraphs,  the  blood  of  the  peptonized  animal  shows 
upon  examination  the  presence  of  an  increased  amount  of  anti- 
thrombin, and  probably  the  loss  or  diminution  in  the  coagula- 
bility of  the  blood  is  due  to  the  excess  of  this  substance.  We  may 
believe,  therefore,  that  the  peptone  solution  has  in  some  way,  di- 
rectly or  indirectly,  stimulated  the  body  to  produce  antithrombin. 
Pick  and  Spiro*  state  that  this  action  of  peptone  solutions  is 
not  due  to  the  peptone  or  the  albumoses  contained  in  it.  When 
obtained  in  purified  form  these  substances  have  no  such  effect. 
They  attribute  the  action  to  a  substance,  derived  probably  from 
the  tissues  used  in  the  preparation  of  the  peptone,  and  for  which 
they  suggest  the  name  of  peptozym. 

In  obtaining  so-called  peptone  plasma  by  injecting  solutions  of  Witte's 
peptone,  of  the  strength  named,  into  the  arteries  of  a  dog  it  happens  sometimes 
that  a  negative  result  is  obtained.  Some  specimens  of  Witte's  peptone  are 
effective  and  some  are  not.  This  fact  accords  with  the  results  of  the  investi- 
gation made  by  Pick  and  Spiro  in  indicating  that  the  reaction  is  not  due  to  the 
peptones  or  proteoses,  but  to  some  unknown  constituent  present  which  may  be 
regarded  as  an  impurity. 

Leech  extracts  differ  from  solutions  containing  peptozym  in 
that  they  prevent  the  clotting  of  the  blood  when  added  to  it  out- 
side the  body.  They  evidently  contain  already  formed  a  substance 
whose  action  prevents  coagulation.  This  substance  is  secreted  by 
the  salivary  glands  of  the  leech.  It  has  been  prepared  from  the 
glands  in  a  more  or  less  pure  form,  and  is  designated  as  hirudin., 
It  is  a  body  belonging  apparently  to  the  groups  of  albumoses  and 
is  supposed  to  antagonize  the  action  of  thrombin.  As  stated  above, 
a  similar  antithrombin  occurs  normally  in  circulating  blood. 

Total  Quantity  of  Blood  in  the  Body. — The  total  quantity  of 
blood  in  the  body  has  been  determined  approximately  for  man 
and  a  number  of  the  lower  animals.  The  method  (Welcker) 
used  in  such  determinations  consists  essentially  in  first  bleeding 
the  animal  as  thoroughly  as  possible  and  weighing  the  quantity 
of  blood  thus  obtained,  and  afterward  washing  out  the  blood- 
*  "Zeitschrift  f.  physiol.  Chemie,"  31,  235,  1900. 


470  BLOOD    AND    LYMPH. 

vessels  with  water  and  estimating  the  amount  of  hemoglobin 
in  the  washings. 

GrShant  ("Journal  de  1'Anat.  et  de  Physiol.,"  1882,  564)  has  devised  an- 
other method  which  may  be  used  upon  the  living  animal,  as  follows  :  A 
specimen  of  blood  is  taken  from  the  animal  and  the  volume  per  cent,  of 
oxygen  is  determined  by  extraction  with  a  gas-pump.  The  animal  is  then 
made  to  breathe  a  known  volume  of  carbon  monoxid  for  a  certain  time,  and 
the  total  amount  of  this  carbon  monoxid  that  is  absorbed  is  ascertained  by 
analysis.  A  second  specimen  of  blood  is  then  taken  and  its  volume  per  cent, 
in  oxygen  is  again  determined.  The  difference  between  this  volume  per  cent, 
of  oxygen  and  that  obtained  before  the  administration  of  the  carbon  monoxid 
gives  the  volume  per  cent,  of  carbon  monoxid  in  the  blood,  since  the  latter 
gas  displaces  an  equal  volume  of  oxygen.  If  the  total  amount  of  carbon 
monoxid  absorbed  by  the  blood  is  indicated  by  V  and  the  volume  per  cent., 
that  is,  the  number  of  c.c.  to  each  100  c.c.  of  blood,  is  indicated  by  v,  then  the 

total  quantity  of  the  blood  will  be  given  by  the  formula  —  X  100. 

The  average  results  obtained  from  numerous  experiments  are 
as  follows:  The  ratio  of  weight  of  blood  to  weight  of  body  is,  in  the 
dog,  7.7  per  cent.;  rabbit  and  cat,  5  per  cent.;  birds,  10  per  cent. 
On  man  we  have  upon  record  two  determinations  on  guillotined 
criminals  made  by  Bischoff,  which  gave  7.7  and  7.2  per  cent. 
Haldane  and  Smith,*  however,  have  devised  a  modification  of 
Gre*hant's  carbon  monoxid  method,  which  they  have  applied  to 
living  men.  The  results  of  some  74  experiments  gave  them  an 
average  value  of  only  5  per  cent,  for  man.  The  distribution  of 
this  blood  in  the  tissues  of  the  body  at  any  time  has  been  esti- 
mated by  Ranke,t  from  experiments  on  freshly  killed  rabbits,  as 
follows : 

Spleen 0.23  per  cent. 

Brain  and  cord 1.24    "       " 

Kidneys 1.63    "       " 

Skin 2.10 

Intestines 6.30 

Bones 8.24 

Heart,  lungs,  and  great  blood-vessels  .......  22.76 

Resting  muscles ; 29.20 

Liver 29.30 

It  will  be  seen  from  inspection  of  this  table  that  in  the  rabbit  the 
blood  of  the  body  is  distributed  at  any  one  time  about  as  follows: 
One-fourth  to  the  heart,  lungs,  and  great  blood-vessels;  one-fourth 
to  the  liver;  one-fourth  to  the  resting  muscles;  and  one-fourth  to  the 
remaining  organs. 

Regeneration  of  the  Blood  after  Hemorrhage. — A  large 
portion  of  the  entire  quantity  of  blood  in  the  body  may  be  lost 

*  Haldane  and  Smith,  "Journal  of  Physiology,"  25,  331,  1900;  also  Zuntz 
and  Pletsch,  "Biochemische  Zeitschrift,"  47,  1908. 

t  Taken  from  Vierordt's  "Anatomische,  physiologische,  und  physikalische 
Daten  und  Tabellen,"  Jena,  1893. 


REGENERATION  AND  HEMORRHAGE. 


471 


suddenly  by  hemorrhage  without  producing  a  fatal  result.  The 
extent  of  hemorrhage  that  may  be  recovered  from  safely  has  been 
investigated  upon  a  number  of  animals.  Although  the  results 
show  more  or  less  individual  variation,  it  may  be  said  that  in  dogs 
a  hemorrhage  of  from  2  to  3  per  cent,  of  the  body-weight*  is  re- 
covered from  easily,  while  a  loss  of  4.5  per  cent.,  more  than  half 
the  entire  blood,  will  probably  prove  fatal.  In  cats  a  hemorrhage 
of  from  2  to  3  per  cent,  of  the  body-weight  is  not  usually  followed 
by  a  fatal  result.  Just  what  percentage  of  loss  may  be  borne  by  the 
human  being  has  not  been  ^determined,  but  it  is  probable  that  a 
healthy  individual  may  recover  without  serious  difficulty  from  the 
loss  of  a  quantity  of  blood  amounting  to  as  much  as  3  per  cent,  of 


Fig.  187. — To  show  the  effect  of  hemorrhage  upon  the  number  of  red  and  white  cor- 
puscles and  the  amount  of  hemoglobin. — (Dawson.)  The  ordinates  express  the  numbera 
of  corpuscles  and  also  the  percentages  of  hemoglobin  as  stated  in  the  figures  to  the  left. 
The  abscissas  give  the  days  after  hemorrhage.  The  experiment  was  made  upon  a  dog  of 
8.1  kgms.  The  hemorrhage,  which  lasted  2.3  minutes,  was  equal  to  4.3  per  cent,  of  the 
body-weight.  An  equal  amount  of  physiological  saline  (NaCl,  0.8  per  cent.)  was  injected 
immediately. 

the  body-weight.  If  a  hemorrhage  has  not  been  fatal,  experi- 
ments on  lower  animals  show  that  the  plasma  of  the  blood  is 
regenerated  with  some  rapidity,  the  blood  regaining  its  normal  vol- 
ume within  a  few  hours  in  slight  hemorrhages,  and  in  from  twenty- 
four  to  forty-eight  hours  if  the  loss  of  blood  has  been  severe;  but 
the  number  of  red  corpuscles  and  the  hemoglobin  are  restored 
more  slowly,  getting  back  to  normal  only  after  a  number  of  days  or 
after  several  weeks.  The  accompanying  curves  illustrate  the  results 
*  Frederic,  "Travaux  du  Laboratoire"  (Universite  de  Liege),  1,  189,  1885. 


472  BLOOD    AND    LYMPH. 

of  a  severe  hemorrhage  (4.3  per  cent,  of  the  body-weight)  followed 
by  transfusion  of  an  equal  volume  of  physiological  saline.  So  far 
as  the  red  corpuscles  and  the  amount  of  hemoglobin  are  concerned, 
it  will  be  noticed  that  the  large  sudden  fall  from  the  hemorrhage, 
first  day,  is  followed  by  a  slower  drop  in  both  factors  during  the 
second  and  third  days.  This  latter  phenomenon  constitutes  what 
is  known  as  the  posthemorrhagic  fall.* 

Blood-transfusion. — Shortly  after  the  discovery  of  the  circu- 
lation of  the  blood  (Harvey,  1628),  the  operation  was  introduced 
of  transfusing  blood  from  one  individual  to  another  or  from  some 
of  the  lower  animals  to  man.  Extravagant  hopes  were  held  as  to 
the  value  of  such  transfusion  not  only  as  a  means  of  replacing  the 
blood  lost  by  hemorrhage,  but  also  as  a  cure  for  various  infirmities 
and  diseases.  Then  and  subsequently  fatal  as  well  as  successful 
results  followed  the  operation.  So  far  as  the  use  of  the  blood  of 
another  animal  is  concerned,  it  is  now  known  to  be  a  dangerous 
undertaking,  mainly  because  the  serum  of  one  animal  may  be 
toxic  to  another  or  cause  a  destruction  of  its  blood  corpuscles. 
Owing  to  this  hemolytic  and  toxic  action,  which  has  previously 
been  referred  to  (p.  424),  the  injection  of  foreign  blood  is  likely  to 
be  directly  injurious  instead  of  beneficial.  In  human  surgery 
modern  technic  (Carrel)  has  overcome  some  of  the  difficulties 
formerly  encounterd  in  the  transfusion  of  blood  from  one  human 
being  to  another.  Anastomoses  may  be  made  between  the  blood- 
vessels of  the  "donor"  and  the  "recipient,"  so  that  the  blood  passes 
from  one  to  the  other  without  coming  into  contact  with  a  foreign 
surface  and,  therefore,  without  danger  of  coagulation  or  the  for- 
mation of  thrombin.  Other  simpler  methods  are  used  success- 
fully for  the  same  purpose.  For  example,  the  blood  may  be  taken 
from  the  vein  of  a  "donor"  with  a  syringe,  coagulation  being  pre- 
vented by  the  use  of  a  proper  amount  of  sodium  citrate  solution. 
This  citrated  blood  is  then  introduced  directly  into  a  vein  of  the 
"recipient."  Such  methods  of  transfusion  are  used  very  frequently 
at  the  present  time  and  often  with  good  results.  In  cases  of  loss 
of  blood  from  severe  hemorrhage  it  is  simpler  to  inject  a  neutral 
liquid,  such  as  the  so-called  "physiological  salt  solution" — a  solu- 
tion of  sodium  chlorid  of  such  a  strength  (0.7  to  0.9)  as  will  suffice 
to  prevent  hemolysis  of  the  red  corpuscles.  This  method,  how- 
ever, has  the  disadvantages  that  its  good  effects  are  temporary. 
The  new  fluid  introduced  into  the  circulation  soon  escapes  into  the 
tissues,  rendering  the  latter  edematous.  We  may  explain  this  fact 
on  the  assumption  that  the  filtration  from  the  vessels  into  the 
tissues  is  not  compensated  by  an  absorption  of  water  from  the 
tissues  into  the  blood.  This  latter  act  depends  largely  on  the  low 
*  Dawson,  "American  Journal  of  Phyciology,"  4,  1,  1900. 


BLOOD-TRANSFUSION.  473 

but  steady  osmotic  pressure  exerted  by  the  proteins  of  the  blood 
which,  of  course,  are  much  diluted  when  a  salt  solution  is  transfused 
into  the  veins.  To  overcome  this  difficulty  it  has  been  suggested 
that  solutions  of  gum  arabic  having  the  same  viscosity  as  the 
blood  (6  to  7  per  cent.)  may  be  used,  after  they  are  made  isotonic 
by  the  addition  of  sodium  chlorid  or  sodium  bicarbonate.  Accord- 
ing to  the  reports  made,  transfusions  with  such  solutions  give  more 
favorable  and  permanent  results  than  solutions  containing  only 
crystalloid  bodies.  * 

*  See  Bayliss,  "Proceedings  &oyal  Society,"  89  B,  381,  1916;  also  "Report 
to  Medical  Research  Committee,"  No.  1,  November  25,  1917. 


CHAPTER  XXIV. 
COMPOSITION  AND  FORMATION  OF  LYMPH. 

Lymph  is  a  colorless  liquid  found  in  the  lymph- vessels  as  well 
as  in  the  extravascular  spaces  of  the  body.  All  the  tissue  elements, 
in  fact,  may  be  regarded  as  being  bathed  in  lymph.  To  understand 
its  occurrence  in  the  body  one  has  only  to  bear  in  mind  its  method 
of  origin  from  the  blood.  Throughout  the  entire  body  there  is  a 
rich  supply  of  blood-vessels  penetrating  every  tissue  with  the  ex- 
ception of  the  epidermis  and  some  epidermal  structures,  as  the  nails 
and  the  hair.  The  plasma  of  the  blood  makes  its  way  through  the 
thin  walls  of  the  capillaries,  and  is  thus  brought  into  immedi- 
ate contact  with  the  tissues,  to  which  it  brings  the  nourishment 
and  oxygen  of  the  blood  and  from  which  it  removes  the  waste 
products  of  metabolism.  This  extravascular  lymph  is  col- 
lected into  small  capillary  spaces  which,  in  turn,  open  into  defi- 
nite lymphatic  vessels.  It  is  still  a  question  among  the  his- 
tologists  whether  the  lymph- vessels  form  a  closed  system  or  are  in 
direct  anatomical  connection  with  the  tissue  spaces.  Modern 
work*  supports  the  view  that  the  lymph  capillaries  are  closed 
vessels  similar  in  structure  to  the  blood  capillaries.  They  end 
in  the  tissues  generally,  but  are  not  in  open  communication  with 
the  spaces  between  the  cellular  elements  or  with  the  larger  serous 
cavities  between  the  folds  of  the  peritoneum,  pleura,  etc.,  or 
with  the  spaces  between  the  meningeal  membranes  surrounding 
the  central  nervous  system.  From  the  physiological  standpoint, 
however,  the  liquid  in  these  latter  cavities,  the  cerebrospinal 
liquid  and  the  liquid  bathing  the  tissue  elements,  must  be 
regarded  as  a  part  of  the  general  supply  of  lymph  and  as  being 
in  communication  with  the  liquid  contained  in  the  lymph- 
vessels.  That  is  to  say,  the  water  and  the  dissolved  substances 
contained  in  the  tissue  spaces  interchange  more  or  less  freely 
with  the  lymph  proper  found  in  the  formed  lymph-vessels.  The 
lymph-vessels  unite  to  form  larger  and  larger  trunks,  making 
eventually  one  main  trunk,  the  thoracic  or  left  lymphatic  duct, 

*  See  Sabin,  "American  Journal  of  Anatomy,"  1,  367,  1902,  and  3,  183, 
1904;  also  " General  and  Special  Anatomy  of  the  Lymphatics,"  from  Poirier 
and  Charpy,  translated  by  Leaf,  1904. 

474 


COMPOSITION    AND    FORMATION    OF    LYMPH.  475 

and  a  second  smaller  right  lymphatic  duct,  which  open  into  the 
blood-vessels,  each  on  its  own  side,  at  the  junction  of  the  sub- 
clavian  and  internal  jugular  veins.  While  the  supply  of  lymph 
in  the  lymph-vessels  may  be  considered  as  being  derived  ulti- 
mately entirely  from  the  blood-plasma,  it  is  well  to  bear  in  mind 
that  at  any  given  moment  this  supply  may  be  altered  by  direct 
interchange  with  the  plasma  on  one  side  and  the  extravascular 
lymph  permeating  the  tissue  elements  on  the  other.  The 
intravascular  lymph  may  be  augmented,  for  example,  by  a 
flow  of  water  from  the  bloo^-plasma  into  the  lymph-spaces,  and 
thence  into  the  lymph-vessels,  or  by  a  flow  from  the  tissue 
elements  into  the  lymph-spaces  that  surround  them.  The  lymph 
movement  is  from  the  tissues  to  the  veins,  and  the  flow  is  main- 
tained chiefly  by  the  difference  in  pressure  between  the  lymph 
at  its  origin  in  the  tissues  and  in  the  large  lymphatic  vessels. 
The  continual  formation  of  lymph  in  the  tissues  leads  to  the 
development  of  a  relatively  high  pressure  in  the  lymph  capil- 
laries, and  as  a  result  of  this  the  lymph  is  forced  toward  the 
point  of  lowest  pressure — namely,  the  points  of  junction  of  the 
large  lymph-ducts  with  the  venous  system.  A  brief  discussion 
of  the  factors  concerned  in  the  movement  of  lymph  will  be  found 
in  the  section  on  Circulation.  As  would  be  inferred  from  its 
origin,  the  composition  of  the  intravascular  lymph  is  essentially 
the  same  as  that  of  blood-plasma.  It  contains  the  three  blood 
proteins,  the  extractives  (urea,  fat,  lecithin,  cholesterin,  sugar), 
and  inorganic  salts.  The  salts  are  found  in  the  same  propor- 
tions as  in  the  plasma;  the  proteins  are  usually  stated  to  be 
less  in  amount.  Histological  examination  shows  that  the  lymph 
contains  many  leucocytes  almost  all  of  which  belong  to  the  group 
of  small  lymphocytes.  Red  corpuscles  are  frequently  found, 
especially  when  the  flow  of  lymph  has  been  stimulated  by  arti- 
ficial means.  It  is  believed  usually  that  these  red  corpuscles  are 
not  a  normal  or  constant  element  of  the  lymph,  but  represent,  so 
to  speak,  an  accidental  constituent.  When  red  corpuscles  for 
any  reason  get  through  the  capillary  walls  into  the  tissue-spaces 
they  are  gathered  up  in  the  lymph-stream.  Blood-platelets  seem 
to  be  entirely  lacking.  Lymph,  like  blood,  coagulates  when  removed 
from  the  lymph-vessels.  Ordinarily  the  clotting  is  slower  than 
with  blood,  and  the  clot  is  not  so  firm.  If,  however,  tissue  extract 
is  added  to  the  lymph,  it  clots  rapidly  and  firmly.  Chemical  ex- 
amination shows  that,  like  the  blood,  the  lymph  contains  fibrinogen, 
prothrombin,  antithrombin,  and  calcium  salts.  When  collected 
without  contamination  with  tissue-juice,  its  slower  and  feebler 
clotting  as  compared  with  the  blood  may  be  explained  by  the 
absence  of  the  blood-platelets.  The  composition  of  the  exuda- 


476  BLOOD    AND    LYMPH. 

live  liquids  of  the  body,  such  as  the  pericardial  liquid,  the  syno- 
vial  liquid,  the  aqueous  humor,  the  cerebrospinal  liquid,  etc., 
which  are  sometimes  classed  under  the  general  term  " lymph,"  may 
Vary  greatly;  thus,  the  cerebrospinal  liquid  possesses  no  morpho- 
logical elements,  contains  no  fibrinogen,  and,  therefore,  does  not 
clot,  and,  indeed,  has  only  minute  traces  of  protein  of  any  kind. 

Formation  of  Lymph. — The  careful  researches  of  Ludwig  and 
his  pupils  were  formerly  believed  to  prove  that  the  lymph  is  derived 
directly  from  the  plasma  of  the  blood  mainly  by  nitration  through 
the  capillary  walls.  Emphasis  was  laid  on  the  undoubted  fact  that 
the  blood  within  the  capillaries  is  under  a  pressure  higher  than  that 
prevailing  in  the  tissues  outside,  and  it  was  supposed  that  this  excess 
of  pressure  is  sufficient  to  squeeze  the  plasma  of  the  blood  through 
the  very  thin  capillary  walls.  Various  conditions  that  alter  the 
pressure  of  the  blood  were  shown  to  influence  the  amount  of  lymph 
formed  in  accordance  with  the  demands  of  a  theory  of  nitration. 
Moreover,  the  composition  of  lymph  as  usually  given  seems  to  sup- 
port such  a  theory,  inasmuch  as  the  inorganic  salts  contained  in  it 
are  in  the  same  concentration,  approximately,  as  in  blood-plasma, 
while  the  proteins  are  in  less  concentration,  following  the  well- 
known  law  that  in  the  nitration  of  colloids  through  animal  mem- 
branes the  nitrate  is  more  dilute  than  the  original  solution.  This 
simple  and  apparently  satisfactory  theory  has  been  subjected  to 
critical  examination  within  recent  years,  and  it  has  been  shown  that 
filtration  alone  does  not  suffice  to  explain  the  composition  of  the 
lymph  under  all  circumstances.  At  present  two  divergent  views 
are  held  upon  the  subject.  According  to  some  physiologists,  all 
the  facts  known  with  regard  to  the  composition  of  lymph  may  be 
satisfactorily  explained  if  we  suppose  that  this  liquid  is  formed 
from  blood-plasma  by  the  combined  action  of  the  physical  processes 
of  nitration,  diffusion,  and  osmosis.  According  to  others,  it  is 
believed  that,  in  addition  to  nitration  and  diffusion,  it  is  necessary 
to  assume  an  active  secretory  process  on  the  part  of  the  endothe- 
lial  cells  composing  the  capillary  walls.  The  actual  condition  of  our 
knowledge  of  the  subject  can  be  presented  most  easily  by  briefly 
stating  some  of  the  objections  that  have  been  raised  by  Heidenhain  * 
to  a  pure  filtration-and-diffusion  theory,  and  indicating  how  these 
objections  have  been  met. 

1 .  Heidenhain  showed  by  simple  calculations  that  an  impossible 
formation  of  lymph  would  be  required,  upon  the  filtration  theory, 
to  supply  the  chemical  needs  of  the  organs  in  various  organic  and  in- 
organic constituents.  Thus,  to  take  an  illustration  that  has  been 
much  discussed,  one  kilogram  of  cows'  milk  contains  1.7  gms.  CaO 
and  the  entire  milk  of  twenty-four  hours  would  contain,  in  round 
*  "Archiv  f.  die  gesammte  Physiologic,"  49,  209,  1891. 


COMPOSITION    AND    FORMATION    OF    LYMPH.  4/7 

numbers,  42.5  gms.  CaO.  Since  the  lymph  contains  normally 
about  0.18  part  of  CaO  per  thousand,  IT-  would  require  236  liters  of 
lymph  per  day  to  supply  the  necessary  CaO  to  the  mammary  glands. 
Heidenhain  himself  suggests  that  the  difficulty  in  this  case  may  be 
met  by  assuming  active  diffusion  processes  in  connection  with 
filtration.  If,  for  instance,  in  the  case  cited,  we  suppose  that  the 
calcium  of  the  lymph  is  quickly  combined  by  the  tissues  of  the  mam- 
mary gland,  then  the  diffusion  tension  of  calcium  salts  in  the  tissue 
will  be  kept  at  zero,  and  an  active  diffusion  of  calcium  into  the 
lymph  will  occur  so  long  as  tne  gland  is  secreting.  In  other  words, 
the  gland  will  receive  its  calcium  by  much  the  same  process  as  it 
receives  its  oxygen,  and  will  get  its  daily  supply  from  a  compara- 
tively small  bulk  of  lymph.  Strictly  speaking,  therefore,  the 
difficulty  we  are  dealing  with  here  shows  only  the  insufficiency  of  a 
pure  filtration  theory.  It  seems  possible  that  filtration  and 
diffusion  together  would  suffice  to  supply  the  organs,  so  far  at 
least  as  the  diffusible  substances  are  concerned. 

2.  Heidenhain  found  that  occlusion  of  the  inferior  vena  cava 
causes  not  only  an  increase  in  the  flow  of  lymph — as  might  be  ex- 
pected, on  the  filtration  theory,  from  the  consequent  rise  of  pressure 
in  the  capillary  regions — but  also  an  increased  concentration  in  the 
percentage  of  protein  in  the  lymph.     This  latter  fact  has  been 
satisfactorily  explained  by  the  experiments  of  Starling.*     Accord- 
ing to  this  observer,  the  lymph  formed  in  the  liver  is  normally  more 
concentrated  than  that  of  the  rest  of  the  body.     The  occlusion  of 
the  vena  cava  causes  a  marked  rise  in  the  capillary  pressure  in  the 
liver,  and  most  of  the  increased  lymph-flow  under  these  circum- 
stances comes  from  the  liver;    hence  the  greater  concentration. 
The  results  of  this  experiment,  therefore,  do  not  antagonize  the 
filtration-and-diffusion  theory. 

3.  Heidenhain  discovered  that  extracts  of  various  substances, 
which  he  designated  as  "  lymphagogues  of  the  first  class/'  cause  a 
marked  increase  in  the  flow  of  lymph  from  the  thoracic  duct,  the 
lymph  being  more  concentrated  than  normal,  and  the  increased  flow 
continuing  for  a  long  period.     Nevertheless,  these  substances  cause 
little,  if  any,  increase  in  general  arterial  pressure;  in  fact,  if  injected 
in  sufficient  quantity  they  produce  usually  a  fall  of  arterial  pressure. 
The  substances  belonging  to  this  class  comprise  such  things  as  pep- 
tone, egg-albumin,  extracts  of  liver  and  intestine,  and  especially 
extracts  of  the  muscles  of  crabs,  crayfish,  mussels,  and  leeches. 
Heidenhain    supposed    that    these    extracts    contain    an   organic 
substance  which  acts  as  a  specific  stimulus  to  the  endothelial  cells 
of  the  capillaries  and  increases  their  secretory  action.     The  results 
of  the  action  of  these  substances  has  been  differently  explained  by 

*  "Journal  of  Physiology,"  16,  234,  1894. 


478 


BLOOD    AND    LYMPH. 


those  who  are  unwilling  to  believe  in  the  secretion  theory.  Starling* 
finds  experimentally  that  the  increased  flow  of  lymph  in  this  case,  as 
after  obstruction  of  the  vena  cava,  comes  mainly  from  the  liver. 
There  is  at  the  same  time  in  the  portal  area  an  increased  pressure 
that  may  account  in  part  for  the  greater  flow  of  lymph;  but,  since 
this  effect  upon  the  portal  pressure  lasts  but  a,  short  time,  while 
the  greater  flow  of  lymph  may  continue  for  one  or  two  hours,  it  is 
obvious  that  this  factor  alone  does  not  suffice  to  explain  the  result 
of  the  injections.  Starling  suggests,  therefore,  that  these  extracts 
act  pathologically  upon  the  blood  capillaries,  particularly  those  of 
the  liver,  and  render  them  more  permeable,  so  that  a  greater 
quantity  of  concentrated  lymph  flows  through  them.  Starling's 
explanation  is  supported  by  the  experiments  of  Popoff.f  According 
to  this  observer,  if  the  lymph  is  collected  simultaneously  from  the 
lower  portion  of  the  thoracic  duct,  which  conveys  the  lymph  from 
the  abdominal  organs,  and  from  the  upper  part,  which  contains  the 
lymph  from  the  head,  neck,  etc.,  it  is  found  that  injection  of 
peptone  increases  the  flow  only  from  the  abdominal  organs.  Popoff 
finds  also  that  the  peptone  causes  a  dilatation  in  the  intestinal 
circulation  and  a  marked  rise  in  the  portal  pressure.  At  the  same 
time  there  is  some  evidence  of  injury  to  the  walls  of  the  blood- 
vessels from  the  occurrence  of  extravasations  in  the  intestine.  As 
far,  therefore,  as  the  action  of  the  lymphagogues  of  the  first  class  is 
concerned,  it  may  be  said  that  the  advocates  of  the  filtration-and- 
diffusion  theory  have  suggested  a  plausible  explanation  in  accord 
with  their  theory.  The  facts  emphasized  by  Heidenhain  with 
regard  to  this  class  of  substances  do  not  compel  us  to  assume  a 
secretory  function  for  the  endothelial  cells. 

4.  Injection  of  certain  crystalline  substances — such  as  sugar, 
sodium  chlorid  and  other  neutral  salts — causes  a  marked  increase 
in  the  flow  of  lymph  from  the  thoracic  duct.  The  lymph  in  these 
cases  is  more  dilute  than  normal,  and  the  blood-plasma  also  becomes 
more  watery,  thus  indicating  that  the  increase  in  water  comes  from 
the  tissues  themselves.  Heidenhain  designated  these  bodies  as 
"lymphagogues  of  the  second  class."  His  explanation  of  their 
action  is  that  the  crystalloid  materials  introduced  into  the  blood  are 
eliminated  by  the  secretory  activity  of  the  endothelial  cells,  and  that 
they  then  attract  water  from  the  tissue  liquid,  thus  augmenting 
the  flow  of  lymph.  These  substances  cause  but  little  change  in 
arterial  blood-pressure ;  hence  Heidenhain  thought  that  the  greater 
flow  of  lymph  can  not  be  explained  by  an  increased  filtration. 
Starling  f  has  shown,  however,  that,  although  these  bodies  may  not 

*  "Journal  of  Physiology,"  17,  30,  1894. 
t  "Centralblatt  f .  Physiologic,"  9,  No.  2,  1895. 
Loc.  tit. 


COMPOSITION    AND    FORMATION    OF    LYMPH.  479 

seriously  alter  general  arterial  pressure,  they  may  greatly  augment 
intracapillary  pressure,  particularly  in  the  abdominal  organs.  His 
explanation  of  the  greater  flow  of  lymph  in  these  cases  is  as  follows : 
"On  their  injection  into  the  blood  the  osmotic  pressure  of  the  circu- 
lating fluid  is  largely  increased.  In  consequence  of  this  increase 
water  is  attracted  from  lymph  and  tissues  into  the  blood  by  a  process 
of  osmosis,  until  the  osmotic  pressure  of  the  circulating  fluid  is 
restored  to  normal.  A  condition  of  hydremic  plethora  is  thereby 
produced,  attended  with  a  rise  of  pressure  in  the  capillaries  generally, 
especially  in  those  of  the  abctominal  viscera.  This  rise  of  pressure 
will  be  proportional  to  the  increase  in  the  volume  of  the  blood,  and 
therefore  to  the  osmotic  pressure  of  the  solutions  injected.  The 
rise  of  capillary  pressure  causes  great  increase  in  the  transudation 
of  fluid  from  the  capillaries,  and  therefore  in  the  lymph-flow  from 
the  thoracic  duct."  This  explanation  is  well  supported  by  experi- 
ments, and  seems  to  obviate  the  necessity  of  assuming  a  secretory 
action  on  the  part  of  the  capillary  walls. 

5.  Numerous  other  experiments  have  been  devised  by  Heidenhain 
and  his  followers  to  show  that  the  physical  laws  of  filtration,  diffu- 
sion, and  osmosis  do  not  suffice  to  explain  the  production  of  lymph ; 
but  in  all  these  cases  possible  explanations  have  been  suggested 
in  terms  of  the  physical  laws,  so  that  it  may  be  said  that  the 
facts  do  not  compel  us  to  assume  a  secretory  activity  on  the 
part  of  the  endothelial  cells  of  the  capillaries.  Asher*  and  his 
co-workers  have  brought  forward  many  facts  to  show  that  the  lymph 
is  controlled  as  to  its  amount  by  the  activity  of  the  tissue  elements 
and  may  be  considered  as  a  product  of  the  activity  of  the  tissues,  as 
a  secretion,  in  fact,  of  the  working  cells.  When  the  salivary  glands, 
the  liver,  etc.,  are  in  greater  functional  activity  the  flow  of  lymph 
from  them  is  increased  beyond  doubt,  so  that  the  activity  of  the 
organs  does  influence  most  markedly  the  production  of  lymph. 
Most  physiologists,  however,  prefer  to  explain  this  relationship  on 
the  view  suggested  by  Koranyi,  Starling,  and  others, — namely,  that 
in  the  metabolic  changes  of  functional  activity  the  large  molecules 
of  protein,  fat,  etc.,  are  broken  down  to  a  number  of  simpler  ones, 
the  number  of  particles  in  solution  is  increased  and  therefore  the 
osmotic  pressure  is  increased.  According  to  most  observers 
the  molecular  concentration  of  the  lymph  in  the  thoracic  duct, 
and,  therefore,  the  osmotic  pressure,  is  greater  than  that  of  the 
blood.  Thus  Botazzi,t  in  one  experiment,  reports  that  the 
lowering  of  the  freezing-point  of  the  blood-serum  was  A  =0.595° 
C.,  while  that  of  the  lymph  from  the  thoracic  duct  of  the  same 

*  "Zeitschrift  f.  Biologie,"  vols.  xxxvi-xl,  1897  to  1900. 
t  Quoted  from  Magnus,  "Handbuch  der  Biochemie,"  1908,  vol.  ii.2  (For- 
mation of  Lymph). 


BLOOD    AND    LYMPH. 

animal  was  A  =  0.615°  C.  Back  in  the  tissues,  where  phys- 
iological oxidations  are  going  on,  this  difference  is  probably 
greater,  and  greater  in  proportion  to  the  activity  of  the  tissues. 
We  can  understand  that  in  this  way  functional  activity  of  an 
organ  may  result  in  attracting  more  water  from  the  blood-capil- 
laries into  the  tissue  spaces  and  may  thus  cause  an  augmented 
'flow  of  lymph.  It  is  to  be  borne  in  mind  that  the  liquid  of  the 
tissues  may  be  drained  off  not  only  through  the  lymph-vessels 
but  also  through  the  blood-vessels.  That  liquids  injected  directly 
into  the  tissues  or  special  substances  dissolved  in  such  liquids  may 
be  absorbed  directly  by  the  blood  has  long  been  known.  Magendie, 
for  example,  proved  that  when  a  poison  was  injected  into  an  organ 
which  was  connected  with  the  rest  of  the  body  only  by  its  blood- 
vessels, the  animal  quickly  showed  the  symptoms  of  a  correspond- 
ing intoxication.  Ordinary  hypodermic  injections  are  absorbed 
much  more  quickly  into  the  general  circulation  than  would  be 
the  case  if  they  were  obliged  to  traverse  the  lymph-vessels  and 
enter  the  blood  through  the  thoracic  duct.  Meltzer  has  shown 
that  this  absorption  by  the  blood  from  the  tissue  spaces  takes 
place  with  especial  promptness  if  the  injection  is  made  into  a 
mass  of  muscular  tissue. 

The  liquid  in  the  extravascular  tissue  spaces  is,  in  fact,  sub- 
ject to  a  play  of  influences  from  several  sides,  and  it  is  the  bal- 
ance among  these  competing  influences  which  determines  at  any 
time  the  amount  and  composition  of  this  tissue  lymph.  Thus, 
the  supply  of  this  liquid  is  furnished,  on  the  one  hand,  by  water 
and  dissolved  substances  coming  to  it  from  the  blood  in  the 
capillaries,  on  the  other  hand,  by  water  and  dissolved  substances 
derived  from  the  great  reservoir  contained  in  the  tissue  cells. 
The  amount  of  the  tissue  lymph  is  continually  depleted  on  the 
other  side  by  water  and  dissolved  substances  passing  back  into 
the  capillaries,  or  into  the  tissue  elements,  or,  finally,  into  the 
lymph  capillaries.  In  fact,  we  may  assume  that  as  blood  flows 
through  the  capillaries  of  any  tissue  there  is  a  twofold  movement  of 
water;  a  movement  of  water  from  the  inside  of  the  capillaries  to 
the  outside,  this  flow  being  due  to  filtration,  that  is,  to  the  excess 
of  pressure  inside  the  capillary,  and  a  movement  of  water  from  the 
outside  to  the  inside  of  the  capillaries,  this  flow  being  due  to  absorp- 
tion caused  by  the  greater  osmotic  pressure  of  the  blood  within  the 
capillaries.  An  important  factor  in  this  absorption  is  the  osmotic 
pressure  exerted  by  the  proteins  of  the  blood,  a  small  but  constant 
factor.  Under  usual  conditions  we  may  assume  that  the  filtration 
stream  exceeds  the  absorption  stream,  so  that  the  blood  flows  away 
from  the  tissue  slightly  more  concentrated.  The  water  lost  by  fil- 
tration is  picked  up  by  the  lymphatics  and  returned  to  the  blood 
by  way  of  the  right  and  left  lymphatic  ducts. 


ro.M  POSITION    AND    FORMATION    OF    LYMPH.  481 

Summary  of  the  Factors  Controlling  the  Flow  of  Lymph.— 
We  rriuy  adopt,,  provisionally  at,  least,  the;  so-called  mechanical, 
theory  of  the  origin  of  lymph.  Upon  this  theory  the  forces  in 
activity  are,  first,  the  intracupillary  pressure  tending  to  filter 
the  plasma  through  the  eiidotholial  cells  composing  the  walls 
of  the  capillaries,  and  second,  that  form  of  molecular  energy  which 
gives  rise  to  the  phenomena  of  diffusion  and  osmotic  pressure. 
By  the  action  of  this  force,  the  flow  of  water  from  one  place  to 
another  is  influenced  in  accordance  with  the  difference  in  concen- 
tration of  the  dissolved  substances.  These  two  forces  acting 
everywhere  control  primarily  the  amount  and  composition  of  the 
lymph;  but  still  another  factor  must  be  considered;  for  when  we 
come  to  examine  the  flow  of  lymph  in  different  parts  of  the  body 
striking  differences  are  found.  It  has  been  shown,  for  instance, 
that  in  the  limbs,  under  normal  conditions,  the  flow  is  extremely 
scanty,  while  from  the  liver  and  the  intestinal  area  it  is  relatively 
abundant.  In  fact,  the  lymph  of  the  thoracic  duct  may  be  con- 
sidered as  being  derived  almost  entirely  from  the  latter  two 
regions.  Moreover,  the  lymph  from  the  liver  is  characterized  by 
a  greater  percentage  of  proteins.  To  account  for  these  differences 
Starling  suggests  the  plausible  explanation  of  a  variation  in  permea- 
bility in  the  capillary  walls.  This  factor  is  evidently  one  of  great 
importance,  although  it  is  not  possible  to  state  the  character  of  the 
changes  supposed  to  occur.  One  helpful  suggestion  that  rests 
upon  experimental  evidence  is  that  the  concentration  of  bases, 
especially  of  the  calcium,  contained  in  the  substance  of  the  vessel- 
walls,  affects  greatly  their  physical  properties  and  permeability. 
It  is  evident  that  constituents  of  this  kind  may  vary  with  the 
character  of  the  food,  or  in  general  with  the  composition  of  the 
blood.  The  idea  that  the  permeability  of  the  capillaries  may  vary 
under  different  conditions  has  long  been  used  in  pathology  to 
explain  the  production  of  that  excess  of  lymph  which  gives  rise 
to  the  condition  of  dropsy  or  edema.  The  theories  and  experi- 
ments made  in  connection  with  this  pathological  condition  have, 
in  fact,  a  direct  bearing  upon  the  theories  of  lymph  formation.* 
Under  normal  conditions  the  lymph  is  drained  off  as  it  is  formed, 
while  under  pathological  conditions  it  may  accumulate  in  the 
tissues  owing  either  to  an  excessive  formation  of  lymph,  or  to  some 
diminution  in  the  process  of  absorption,  or  to  some  interruption  in 
its  circulation. 

The  scanty  flow  of  lymph  from  the  limbs  has  been  referred 
by  Magnus  f  to  another  possible  cause,  namely,  to  the  great 

*  Consult  Mcltzer,  "Edema"  ("Harrington  Lectures"),  "American  Medi- 
cine," 8,  Nos.  1,  2,  4,  and  5,  1904. 
t  Magnus,  Loc.  cit. 

31 


482  BLOOD    AND    LYMPH. 

capacity  of  the  muscular  tissue  to  imbibe  water  (and  salts). 
According  to  this  author  the  tissues,  particularly  the  muscular 
tissues,  constitute  great  reservoirs  in  which  excess  of  water  and 
salts  may  be  stored.  If,  for  example,  a  hypotonic  solution  of 
sodium  chloride  is  injected  into  the  circulation,  most  of  the 
water  added  will  be  removed  from  the  circulation  by  imbibition 
into  the  muscular  tissues.  In  the  limbs,  with  their  large  supply 
of  muscular  tissue,  it  may  be  that  lymph  is  formed  as  elsewhere 
from  the  blood  plasma,  but  it  is  held  back  from  the  lymph-vessels 
by  absorption  into  the  muscular  mass. 

From  the  foregoing  considerations  it  is  evident  that  changes 
in  capillary  pressure,  however  produced,  may  alter  the  flow  of 
lymph  from  the  blood-vessels  to  the  tissues,  by  increasing  or 
decreasing,  as  the  case  may  be,  the  amount  of  nitration;  changes  in 
the  composition  of  the  blood,  such  as  follow  periods  of  digestion, 
will  cause  diffusion  and  osmotic  streams  tending  to  equalize  the 
composition  of  blood  and  lymph;  and  changes  in  the  tissues  them- 
selves following  upon  physiological  or  pathological  activity  will 
also  disturb  the  equilibrium  of  composition,  and,  therefore,  set  up 
diffusion  and  osmotic  currents.  In  this  way  a  continual  interchange 
is  taking  place  by  means  of  which  the  nutrition  of  the  tissues  is 
effected,  each  according  to  its  needs.  The  details  of  this  interchange 
must  of  necessity  be  very  complex  when  we  consider  the  possibilities 
of  local  effects  in  different  parts  of  the  body.  The  total  effects  of 
general  changes,  such  as  may  be  produced  experimentally,  are 
simpler,  and,  as  we  have  seen,  are  explained  satisfactorily  by  the 
physical  and  chemical  factors  enumerated. 


SECTION  V. 

PHYSIOLOGY  OF  THE  ORGANS  OF  CIRCULA- 
TION OF  THE, BLOOD  AND  LYMPH. 

The  heart  and  the  blood-vessels  form  a  closed  vascular  system 
Containing  a  certain  amount  of  blood.  This  blood  is  kept  in  endless 
circulation  mainly  by  the  force  of  the  muscular  contractions  of  the 
heart.  But  the  bed  through  which  it  flows  varies  greatly  in  width 
at  different  parts  of  the  circuit,  and  the  resistance  offered  to  the 
moving  blood  is  very  much  greater  in  the  capillaries  than  in  the 
large  vessels.  It  follows  from  the  irregularities  in  size  of  the  chan- 
nels through  which  it  flows  that  the  blood-stream  is  not  uniform  in 
character  throughout  the  entire  circuit;  indeed,  just  the  opposite  is 
true.  From  point  to  point  in  the  branching  system  of  vessels  the 
blood  varies  in  regard  to  its  velocity,  its  head  of  pressure,  etc. 
These  variations  are  connected  in  part  with  the  fixed  structure  of  the 
system  and  in  part  are  dependent  upon  the  changing  properties  of 
the  living  matter  of  which  the  system  is  composed.  It  is  con- 
venient to  consider  the  subject  under  three  general  heads:  (1) 
The  purely  physical  factors  of  the  circulation, — that  is,  the  me- 
chanics and  hydrodynamics  of  the  flow  of  a  definite  quantity  of 
blood  through  a  set  of  fixed  tubes  of  varying  caliber  under  certain 
fixed  conditions.  (2)  The  general  physiology  of  the  heart  and  the 
blood-vessels, — that  is,  mainly  the  special  properties  of  the  heart 
muscle  and  the  plain  muscle  of  the  blood-vessels.  (3)  The  innerva- 
tion  of  the  heart  and  the  blood-vessels, — that  is,  the  variations  in 
the  circulation  produced  by  the  action  of  the  nervous  system. 


CHAPTER  XXV. 
THE  VELOCITY  AND  PRESSURE  OF  THE  BLOOD-FLOW. 

The  Circulation  as  Seen  Under  the  Microscope. — It  is  a 

comparatively  easy  matter  to  arrange  a  thin  membrane  in  a  living 
animal  so  that  the  flowing  blood  may  be  observed  with  the  aid  of  a 
microscope.  For  such  a  purpose  one  generally  employs  the  web 
between  the  toes  of  a  frog,  or  better  still  the  mesentery,  lungs,  or 
bladder  of  the  same  animal.  With  a  good  preparation  many 

483 


484  CIRCULATION  OF  BLOOD   AND  LYMPH. 

important  peculiarities  in  the  blood-flow  may  be  observed  directly. 
If  the  field  is  properly  chosen  one  may  see  at  the  same  time  the  flow 
in  arteries,  capillaries,  and  veins.  It  will  be  noticed  that  in  the 
arteries  the  flow  is  very  rapid  and  somewhat  intermittent, — that  is, 
there  is  a  slight  acceleration  of  velocity,  a  pulse,  with  each  heart 
beat.  In  the  capillaries,  on  the  contrary,  the  flow  is  relatively  very 
slow;  the  change  from  the  rushing  arterial  stream  to  the  deliber- 
ate current  in  the  capillaries  takes  place,  indeed,  with  some 
suddenness.  The  capillary  flow,  as  a  rule,  shows  no  pulses  corre- 
sponding with  the  heart  beats,  but  it  may  be  more  or  less  irregular, 
— that  is,  the  flow  may  nearly  cease  at  times  in  some  capillaries, 
while  again  it  becomes  distinct  and  uniform.  In  the  veins  the 
flow  increases  markedly  in  rapidity,  and,  indeed,  it  may  be  ob- 
served that  the  larger  the  vein,  the  more  rapid  is  the  flow.  There 
is  not,  however,  as  a  rule,  any  indication  of  an  intermittence  or 
pulse  in  this  flow — the  velocity  is  entirely  uniform.  In  both 
arteries  and  veins  it  will  be  noticed  that  the  red  corpuscles  form  a 
solid  column  or  core  in  the  middle  of  the  vessel,  and  that  between 
them  and  the  inner  wall  there  is  a  layer  of  plasma  containing  only, 
under  normal  conditions,  an  occasional  leucocyte.  The  accumula- 
tion of  corpuscles  in  the  middle  of  the  stream  makes  what  is  known 
as  the  axial  stream,  while  the  clear  layer  of  plasma  is  designated  as 
the  inert  layer.  The  phenomenon  is  readily  explained  by  physical 
causes.  As  the  blood  flows  rapidly  through  the  small  vessels  the 
layers  nearer  the  wall  are  slowed  by  adhesion,  so  that  the  greatest 
velocity  is  attained  in  the  middle  or  axis  of  the  vessel.  The  cor- 
puscles, being  heavier  than  the  plasma,  are  drawn  into  this  rapid 
part  of  the  current.  It  has  been  shown  by  physical  experiments 
that,  when  particles  of  different  specific  gravities  are  present  in  a 
liquid  flowing  rapidly  through  tubes,  the  heavier  particles  will  be 
found  in  the  axis  and  the  lighter  ones  toward  the  periphery.  In 
accordance  with  this  fact,  leucocytes,  which  are  lighter  than  the 
red  corpuscles,  may  be  found  in  the  inert  layer.  When  the  con- 
ditions become  slightly  abnormal  (incipient  inflammation)  the 
leucocytes  increase  in  number  in  the  inert  layer  sometimes  to  a 
very  great  extent,  owing  apparently  to  some  alteration  in  the 
endothelial  walls  whereby  the  leucocytes  are  rendered  more  ad- 
hesive. The  accumulation  of  the  leucocytes  in  conditions  of  in- 
flammation and  their  migration  through  the  walls  into  the  sur- 
rounding tissues  are  described  in  works  on  Pathology. 

The  Velocity  and  Volume  of  the  Blood-flow. — The  microscopical 
observations  described  above  show  that  the  velocity  of  the  blood- 
current  varies  widely,  being  rapid  in  the  arteries  and  veins  arid  slow 
in  the  capillaries.  To  ascertain  the  actual  velocity  in  the  larger 
vessels  and  the  variations  in  vessels  of  different  sizes  experimental 
determinations  are  necessary.  While  the  general  principle  involved 


VELOCITY    AND    PRESSURE    OF    BLOOD-FLOW. 


485 


in  these  determinations  is  simple,  their  actual  execution  in  an 
experiment  is  attended  with 
some  difficulties,  and  various 
devices  have  been  adopted. 
The  most  direct  method  per- 
haps is  that  used  in  the  in- 
strument devised  by  Ludwig, — 
namely,  the  stromuhr.  The  prin- 
ciple used  is  to  cut  an  artery 
or  vein  of  a  known  size  and,,de- 
termine  how  much  blood  flows 
out  in  a  given  time.  We  may 
define  the  velocity  of  the  blood 
at  any  point  as  the  length  of 
the  column  of  blood  flowing  by 
that  point  in  a  second.  If  we 
cut  the  artery  there  a  cylindri- 
cal column  of  blood  of  a  defi- 
nite length  and  with  a  cross-area 
equal  to  that  of  the  lumen  of 
the  artery  will  flow  out  in  a 
second.  The  volume  of  the 
outflow  can  be  determined  di- 
rectly by  catching  the  blood. 
Knowing  this  volume  and  the 
cross-area  of  the  artery,  we  can 
determine  the  length  of  the 
column — that  is,  the  velocity 
of  the  flow — since  in  a  cylinder 
the  volume,  V,  is  equal  to  the 
product  of  the  length  into  the 
cross-area. 


V  =  length  X  cross-area,  or 
len^th  -  croslarea 


Fig.  188. — Lud wig's  stromuhr:  a  and  b, 
The  glass  bulbs;  a  is  filled  with  oil  to  the 
mark  (5  c.c.),  while  6  and  the  neck  are  filled 
with  salt  solution  or  defibrinated  blood ;  p, 
the  movable  plate  by  means  of  which  the 
bulbs  may  be  turned  through  180  degrees, 
c,  c,  for  the  cannulas  inserted  into  the  artery; 
«.  the  thumb  screw  for  turning  the  bulbs; 
h,  the  holder.  When  in  place  the  clamps 
on  the  arteries  are  removed,  blood  flows 
through  c  into  a,  driving  out  the  oil  and 
forcing  the  salt  solution  in  6  into  the  head 
end  of  the  artery  through  c7.  When  the 
blood  entering  a  reaches  the  mark,  the  bulb' 
are  turned  through  180  degrees  so  that  6  lies- 
over  c.  The  blood  flows  into  6  and  drives 
the  oil  back  into  a.  When  it  just  fills  this 
bulb,  they  are  again  rotated  through  180 
degrees,  and  so  on.  The  oil  is  driven  out  of 
and  into  a  a  given  number  of  times,  each 
movement  being  equal  to  an  outflow  of  5  c.c. 
of  blood.  When  the  instrument  has  been 
turned,  say,  ten  times,  50  c.c.  of  blood  have 
flowed  out.  Knowing  the  time  and  the 
caliber  of  the  artery,  the  calculation  is  made 
as  described  in  the  text.  Several  modifi- 
cations of  the  form  of  this  instrument  have 
been  devised.* 


We  cannot,  of  course,  make 
the  experiment  in  this  simple 
way  upon  a  living  animal;  the 
loss  of  so  much  blood  would  at 
once  change  the  physical  and  physiological  conditions  of  the  circula- 
tion, and  would  give  us  a  set  of  conditions  at  the  end  of  the  experi- 
ment different  from  those  at  the  beginning.  By  means  of  the 
stromuhr,  however,  this  experiment  can  be  made,  with  this  important 

*  A  modification  by  Tigerstedt  is  described  in  the  "  Skandinavisches 
Archiv  f.  Physiol.,"  3,  152,  1891.  One  by  Burton-Opitz  in  the  "Arch.  f.  d. 
ges.  Physiologic,"  121,  151,  1908- 


486 


CIRCULATION    OF    BLOOD    AND    LYMPH. 


variation,  that  the  blood  that  flows  from  the  central  end  of  the  cut 
artery  is  returned  to  the  peripheral  end  of  the  same  artery,  so  that 
the  circulation  is  not  blocked  nor  deprived  of  its  normal  volume  of 
liquid.  The  instrument,  as  is  explained  in  the  legend  of  Fig.  188, 
measures  the  volume  of  blood  that  flows  out  of  the  cut  end  of  an 
artery  in  a  definite  time.  The  calculation  for  velocity  is  made  as 

follows:  Suppose  that  the  capacity 
of  the  bulb  is  5  c.c.,  and  that  in  the 
experiment  it  has  been  filled  10 
times  in  50  seconds, — i.  e.,  the  bulbs 
have  been  reversed  10  times;  then 
obviously  10  X  5  or  50  c.c.  have 
flowed  out  of  the  artery  in  this 
time,  or  1  c.c.  in  1  second.  The 
diameter  of  the  vessel  can  be  meas- 
ured, and  if  found  equal,  say,  to  2 
mms.,  then  its  cross-area  is  -r2  = 
3.15  X  1  =  3.15.  Since  1  c.c.  equals 
1000  c.mm.,  the  length  of  our  cyl- 
inder of  blood  would  be  given  by 
the  quotient  of  |^?  =  317  mms. 
So  that  the  blood  in  this  case  was 
moving  with  the  velocity  of  317 
mms.  per  second.  Another  instru- 
ment that  has  been  employed  for 
the  same  purpose  is  the  dromograph 
or  hemodromograph  of  Chauveau. 
This  instrument  is  represented  in 
the  accompanying  figure  (Fig.  189). 
A  rigid  tube  (p-c)  is  placed  in  the 
course  of  the  artery  to  be  examined. 
This  tube  is  provided  with  an  offset 
(a)  the  opening  of  which  is  closed 
with  rubber  dam  (ra).  The  rubber 
dam  is  pierced  by  a  needle  the  lower 
end  of  which  terminates  in  a  small 
plate  lying  in  the  tube  (pi}.  When  the  instrument  is  in  place  and 
the  blood  is  allowed  to  stream  through  the  tube,  it  deflects  the 
needle,  which  turns  on  its  insertion  through  the  rubber  as  a  ful- 
crum. The  angle  of  deflection  of  the  free  end  of  the  needle  may 
be  measured  directly  upon  a  scale  or  it  may  be  transmitted 
through  tambours  and  recorded  upon  a  kymographion.  The  in- 
strument must,  of  course,  be  graduated  by  passing  through  it  cur- 
rents of  known  velocity,  so  that  the  angle  of  deflection  may  be 
expressed  in  terms  of  absolute  velocities.  It  possesses  a  great 
advantage  over  the  stromuhr  in  that  it  gives  not  simply  the  average 


Fig.  189. — Chauveau's  hemodromo- 
graph (after  Langendorff).  The  tube, 
p-c,  is  placed  in  the  course  of  an  ar- 
tery, the  blood  after  removal  of  clamps 
flowing  in  the  direction  shown  by  the 
arrow.  The  current  strikes  the  plate, 
pi,  and  forces  it  to  an  angle  varying 
with  the  velocity.  The  movement  or 
pi  is  transmitted  through  the  stem,  n, 
which  moves  in  a  rubber  membrane 
as  a  fulcrum,  m.  The  angular  move- 
ment of  the  projecting  end  of  n  may 
be  measured  directly  or  may  be  made 
to  act  upon  a  tambour,  as  shown  in 
the  figure,  and  thus  be  transmitted  to 
a  recording  drum. 


VELOCITY    AND    PRESSURE    OF    BLOOD-FLOW.  487 

velocity  during  a  given  time,  but  also  the  variations  in  velocity 
coincident  with  the  heart  beat  or  other  changes  that  may  occur 
during  the  period  of  observation.  By  means  of  instruments  of 
this  kind  it  is  possible  to  determine  not  only  the  velocity  in  any 
large  artery  or  vein  at  a  given  moment,  but  also  the  total  volume 
of  flow  into  or  out  of  an  organ  during  a  given  period  of  time. 
Data  of  the  latter  kind  give  us  an  idea  of  the  relative  quantity  of 
blood  supplied  to  each  organ  and  the  differences  in  this  respect 
between  the  several  organs.  Burton-Opitz*  on  the  basis  of  experi- 
ments made  by  himself  and  Others  gives  the  following  figures,  which 
express  the  blood-supply  per  minute  for  each  100  grams  of  organ: 

Posterior  extremity 5  c.c.  Spleen 58  c.c. 

Skeletal  muscle 12  c.c.  Liver  (venous) 59  c.c. 

Head 20  c.c.  Liver  (total) 84  c.c. 

Stomach 21  c.c.  Brain 136  c.c. 

Liver  (arterial) 25  c.c.  Kidney 150  c.c. 

Intestines 31  c.c.  Thyroid  Gland 560  c.c. 

Mean  Velocity  of  the  Blood-flow  in  the  Arteries,  Veins,  and 
Capillaries. — Actual  determinations  of  the  average  velocity  in  the 
large  arteries  and  veins  give  such  results  as  the  following:  Carotid 
of  horse  (Volkmann),  300  mms.  per  second;  (Chauveau)  297  mms. 
Carotid  of  the  dog  (Vierordt),  260  mms. 

The  flow  in  the  carotid,  as  in  the  other  large  arteries,  is  not, 
however,  uniform;  there  is  a  marked  acceleration  or  pulse  at  each 
systole  of  the  heart  during  which  the  velocity  is  greatly  augmented. 
Thus,  in  the  carotid  of  the  horse  it  has  been  shown  by  the  hemo- 
dromograph  that  during  the  systole  the  velocity  may  reach  520 
mms.  and  may  fall  to  150  mms.  during  the  diastole.  It  is  found,  also, 
that  this  difference  between  the  systolic  velocity  and  the  diastolic 
velocity  tends  to  disappear  as  the  arteries  become  smaller,  and,  as 
was  said  above,  disappears  altogether  in  the  capillaries,  in  which 
the  pulse  caused  by  the  heart  beat  is  lacking.  The  smaller  the  artery, 
therefore,  the  more  uniform  is  the  movement  of  the  blood. 

The  flow  in  the  large  veins  is  uniform  or  approximately 
uniform  and  increases  as  one  approaches  the  heart,  although  the 
velocity  in  the  large  veins  near  the  heart  is  somewhat  slower 
than  in  the  large  arteries  of  the  same  region,  owing  to  the  fact 
that  the  total  area  of  the  venous  bed  is  larger  than  that  of  the 
arterial  bed.  Burton-Opitz f  gives  the  following  average  figures 
obtained  from  experiments  upon  anesthetized  dogs.  Jugular, 
147  mms.;  femoral,  61.6  mms.;  renal,  63  mms.;  mesenteric  vein, 
84.9  mms.  In  the  capillaries,  however,  the  velocity  is  relatively 
very  small.  From  direct  observations  made  by  means  of  the 
microscope  and  from  indirect  observations  in  the  case  of  man, 

*  Burton-Opitz,  "Quarterly  Jour,  of  Experimental  Physiology,"  4, 117, 1911. 
t  Burton-Opitz,  "Am.  Journal  of  Physiology,"  vols.  7  and  9,  and  "Pfliiger's 
Archiv,"  vols.  123  and  124,  1908. 


488 


CIRCULATION    OF   BLOOD    AND    LYMPH. 


the  capillary  velocity  is  estimated  as  lying  between  0.5  mm. 
and  0.9  mm.  per  sec. 

Vierordt  reports  some  interesting  calculations  upon  the  velocity  of  the 
blood,  in  the  capillaries  of  his  own  eye.  Under  suitable  conditions,*  the 
movements'  of  the  corpuscles  in  the  retina  may  be  perceived  in  consequence 
of  the  shadows  that  they  throw  upon  the  rods  and  cones.  The  visual  images 
thus  produced  may  be  projected  upon  a  surface  at  a  known  distance  from  the 
eye  and  the  space  traversed  in  a  given  time  may  be  observed.  The  distance 
actually  covered  upon  the  retina  may  then  be  calculated  by  the  following  con- 
struction, in  which  A-B  =  the  distance  traveled  by  the  projected  image; 
A-n,  the  distance  of  the  surface  from  the  eye;  and  a-n.  the  distance  of  the 

retina  from  the  nodal  point 
of  the  eye.  We  have  then 
the  proportion  db  :  an  :: 

AB:An,  or  ab  =  AB  *  an- 

An 

According  to  this  method, 
Vierordt  calculated  that  the 
velocity  of  the  blood  in  the 
human  capillaries  is  equal  to 
about  0.6  to  0.9  mm.  per 
second. 

In  the  arteries,  more- 
over, it  may  be  observed 
that  the  average  velocity 
diminishes  the  farther 

one  goes  from  the  heart, — that  is,  the  smaller  the  artery, — and 
reaches  its  minimum  when  the  arteries  pass  into  the  capillaries. 
Thus,  Volkmann  reports  for  the  horse  the  following  figures:  Ca- 
rotid, 300  mms.;  maxillary,  232;  metatarsal,  56  mms.  In  the  veins 
also  the  same  fact  holds.  The  smaller  the  vein — that  is,  the  nearer 
it  is  to  the  capillary  region — the  smaller  is  its  velocity,  the  maxi- 


Fig.  190. — Diagram  of  the  eye  to  show  the  con- 
struction used  to  determine  the  size  of  the  retinal 
image  when  the  size  of  the  external  object  is  known: 
n,  The  nodal  point  of  the  eye.  See  text. 


Fig.  191. — Schematic  representation  of  the  relative  velocities  of  the  blood-current  in 
different  parts  of  the  vascular  system:  a,  The  arterial  side,  indicating  the  changes  with 
each  heart  beat  and  the  fall  of  mean  velocity  as  the  arterial  bed  widens;  c,  the  capillary 
region — the  great  diminution  in  velocity  corresponds  with  the  great  widening  of  the  bed ; 
v,  the  venous  side,  showing  the  gradual  increase  toward  the  heart,  and  represented  as 
entirely  uniform,  although,  as  a  matter  of  fact,  the  velocity  in  the  large  veins  is  affected  by 
the  respirations  and  to  a  small  extent  by  the  heart  beat,  owing  to  the  phenomenon  known 
as  the  venous  pulse  (p.  532). 

mum  velocity  being  found  in  the  vena  cava.     The  general  rela- 
tions of  the  velocity  of  the  blood  in  the  arteries,  capillaries,  and 
*  "Archiv  f.  physiologische  Heilkunde/'  15,  255,  1856. 


VELOCITY    AND    PRESSURE    OF    BLOOD-FLOW.  489 

veins  may  be  expressed,  therefore,  by  a  curve  such  as  is  shown 
in  Fig.  191. 

Explanation  of  the  Variations  in  Velocity. — The  general  rela- 
tionship between  the  velocities  in  the  different  parts  of  the  vascular 
system  is  explained  by  the  difference  in  the  width  of  the  bed  in 
which  the  blood  flows.  In  the  systemic  circulation  the  main  stem, 
the  aorta,  branches  into  arteries  which,  taken  individually,  are  smaller 
and  smaller  as  we  approach  the  capillaries.  But  each  time  that 
an  artery  branches  the  sum  of  the  areas  of  the  two  branches  is 
greater  than  that  of  the  main  stem.  The  arterial  system  may  be 
compared,  in  fact,  to  a  tree,  the  sum  of  the  cross-areas  of  all  the 
twigs  is  greater  than  that  of  the  main  trunk.  It  follows,  there- 
fore, that  the  blood  as  it  passes  to  the  capillaries  flows  in  a  bed 
or  is  distributed  in  a  bed  which  becomes  wider  and  wider,  and  as  it 
returns  to  the  heart  in  the  veins  it  is  collected  into  a  bed  that  be- 
comes smaller  as  we  approach  the  heart.  Vierordt  estimates  that 
the  combined  calibers  of  all  the  capillaries  in  the  systemic  circula- 
tion would  make  a  tube  with  a  cross-area  about  800  times  as  large  as 
the  aorta.  If  the  circulation  is  proceeding  uniformly  it  follows 
that  for  any  given  unit  of  time  the  same  volume  of  blood  must 
pass  through  any  given  cross-section  of  the  system, — that  is,  at 
a  given  point  in  the  aorta  or  vena  cava  as  much  blood  must  flow 
by  in  a  second  as  passes  through  the  capillary  region — and  that 
consequently  where  the  cross-section  or  bed  is  widest  the  velocity 
is  correspondingly  diminished.  If  the  capillary  bed  is  800  times 
that  of  the  aorta,  then  the  velocity  in  the  capillaries  is  -g^-g-  of  that 
in  the  aorta, — say,  -g-J-g-  of  320  mms.  or  0.4  mm.  Just  as  a  stream 
of  water  flowing  under  a  constant  head  reaches  its  greatest  velocity 
where  its  bed  is  narrowest  and  flows  more  slowly  where  the  bed 
widens  to  the  dimensions  of  a  pool  or  lake. 

Variations  in  Velocity  with  Changes  in  the  Heart-beat  or 
the  Size  of  the  Vessels. — While  the  above  statement  holds  true  as 
an  explanation  of  the  general  relationship  between  the  velocities  in 
the  arteries,  veins,  and  capillaries  at  any  given  moment,  the  absolute 
velocities  in  the  different  parts  of  the  system  will,  of  course,  vary 
whenever  any  of  the  conditions  acting  upon  the  blood-flow  vary. 
In  the  large  arteries,  as  has  been  said,  there  are  extreme  fluctua- 
tions in  velocity  at  each  heart  beat;  but  if  we  consider  only  the 
average  velocities  it  may  be  said  that  these  will  vary  throughout 
the  system  with  the  force  and  rate  of  the  heart  beat,  or  with  the 
variations  in  size  of  the  small  arteries  and  the  resulting  changes  in 
blood-pressure  in  the  arteries.  Marey*  gives  the  two  following 
laws:  (1)  Whatever  increases  or  diminishes  the  force  with  which 
the  blood  is  driven  from  the  heart  toward  the  periphery  will  cause 
the  velocity  of  the  blood  and  the  pressure  in  the  arteries  to  vary  in 
*  "La  Circulation  du  Sang/'  Paris,  1881,  p.  321. 


490  CIRCULATION    OF    BLOOD    AND    LYMPH. 

the  same  sense.  (2)  Whatever  increases  or  diminishes  the  resis- 
tance offered  to  the  blood  in  passing  from  the  arteries  (to  the  veins) 
will  cause  the  velocity  and  the  arterial  pressure  to  vary  in  an 
inverse  sense  as  regards  each  other.  That  is,  an  increased  re- 
sistance diminishes  the  velocity  in  the  arteries  while  increasing 
the  pressure,  and  vice  versa. 

The  Time  Necessary  for  a  Complete  Circulation  of  the 
Blood. — It  is  a  matter  of  interest  in  connection  with  many  physio- 
logical questions  to  have  an  approximate  idea  of  the  time  necessary 
for  the  blood  to  make  a  complete  circuit  of  the  vascular  system, — 
that  is,  starting  from  any  one  point  to  determine  how  long  it  will 
take  for  a  particle  of  blood  to  arrive  again  at  the  same  spot.  In 
considering  such  a  question  it  must  be  borne  in  mind  that  many 
different  paths  are  open  to  the  blood,  and  that  the  time  for  a 
complete  circulation  will  vary  somewhat  with  the  circuit  actually 
followed.  For  example,  blood  leaving  the  left  ventricle  may  pass 
through  the  coronary  system  to  the  right  heart  and  thence  through 
the  pulmonary  system  to  the  left  heart  again,  or  it  may  pass  to  the 
extremities  of  the  toes  before  getting  to  the  right  heart,  or  it  may  pass 
through  the  intestines,  in  which  case  it  will  have  to  traverse  three 
capillary  areas  before  completing  the  circuit.  It  is  obvious,  there- 
fore, that  any  figures  obtained  can  only  be  regarded  as  approxima- 
tions more  or  less  exact.  The  experiments  that  have  been  made, 
however,  are  valuable  in  indicating  how  very  rapidly  any  substance 
that  enters  the  blood  may  be  distributed  over  the  body.  The 
method  first  employed  by  Hering  was  to  inject  into  the  jugu- 
lar vein  of  one  side  a  solution  of  potassium  ferrocyanid,  and  then 
from  time  to  time  specimens  of  blood  were  taken  from  the  jugular 
vein  of  the  opposite  side.  The  first  specimen  in  which  the  ferrocy- 
anid could  be  detected  by  its  reaction  with  iron  salts  gave  the  least 
time  necessary  for  a  complete  circuit.  The  method  was  subse- 
quently improved  in  its  technical  details  by  Vierordt,  and  such 
results  as  the  following  were  obtained:  Dog,  16.32  seconds;  horse, 
28.8  seconds;  rabbit,  7.46  seconds;  man  (calculated),  23  seconds. 
The  time  required  is  less  in  the  small  than  in  the  large  animals,  and 
Hering  and  Vierordt  concluded  that  in  general  it  requires  from  26  to 
28  beats  of  the  heart  to  effect  a  complete  circulation.  Stewart  has 
devised  a  simpler  and  better  method,*  based  upon  the  electrical  con- 
ductivity of  the  blood.  If  a  solution  of  a  neutral  salt,  such  as  sodium 
chlorid,  more  concentrated  than  the  blood,  is  injected  into  the  circu- 
lation, the  conductivity  of  the  blood  is  increased.  If  the  injection  is 
made  at  a  given  moment  and  a  portion  of  the  vessel  to  be  examined 
is  properly  connected  with  a  galvanometer  so  as  to  measure  the  elec- 
trical conductivity  through  it,  then  the  instant  that  the  solution  of 
salt  reaches  this  latter  vessel  the  fact  will  be  indicated  by  a  deflection 
*"  Journal  of  Physiology,"  15,  1,  1894. 


VELOCITY    AND    PRESSURE    OF    BLOOD-FLOW.  491 

of  the  galvanometer.  Using  this  method,  Stewart  was  able  to  show 
that  in  the  lesser  circulation  (the  pulmonary  circuit)  the  velocity 
is  very  great  compared  with  that  of  the  systemic  circulation — 
only  about  one-fifth  of  the  time  required  for  a  complete  circuit 
is  spent  in  the  lesser  circulation.  Attention  may  also  be  called  to 
the  fact  that  the  important  part  of  the  circulation,  as  regards  the 
nutritive  activity  of  the  blood,  is  the  capillary  path.  It  is  while 
flowing  through  the  capillaries  that  the  chief  exchange  of  gases 
and  food  material  takes  place.  The  average  length  of  a  capillary 
is  estimated  at  0.5  mm.;  s6  that  with  a  velocity  of  0.5  mm.  per 
second  the  average  duration  of  the  flow  of  any  particle  of  blood 
through  the  capillary  area  is  only  about  1  sec. 

The  Pressure  Relations  in  the  Vascular  System. — That  the 
blood  is  under  different  pressures  in  the  several  parts  of  the  vascu- 
lar system  has  long  been  known  and  is  easily  demonstrated.  When 
an  artery  is  cut  the  blood  flows  out  in  a  forcible  stream  and  with 
spurts  corresponding  to  the  heart  beats.  When  a  large  vein  is 
wounded,  on  the  contrary,  although  the  blood  flows  out  rapidly, 
the  stream  has  little  force.  Exact  measurements  of  the  hydrostatic 
pressure  under  which  the  blood  exists  in  the  large  arteries  and  veins 
were  first  published  by  Rev.  Dr.  Stephen  Hales,  an  English  clergy- 
man, in  his  famous  book  entitled  "  Statical  Essays,  containing 
Hsemosta  ticks,"  1733.*  This  observer  measured  the  static  pressure 
of  the  blood  in  the  arteries  and  veins  by  the  simplest  direct  method 
possible.  After  tying  the  femoral  artery  in  a  horse  he  connected 
it  to  a  glass  tube  9  feet  in  length.  On  opening  the  vessel  the  blood 
mounted  in  the  tube  to  a  height  of  8  feet  3  inches,  showing  that 
normally  in  the  closed  artery  the  blood  is  under  a  tension  or  pressure 
sufficient  to  support  the  weight  of  a  column  of  blood  of  this  height. 
A  similar  experiment  made  upon  the  vein  showed  a  rise  of  only  12 
inches. 

Methods  of  Recording  Blood-pressure. — Since  Hales's  work 
the  chief  improvements  in  method  which  have  marked  and  caused 
the  development  of  this  part  of  the  subject  have  been  the  application 
of  the  mercury  manometer  by  Poiseuillef  (1828),  the  invention  of 
the  recording  manometer  and  kymographion  by  Ludwigf  (1847), 
and  the  later  numerous  improvements  by  many  physiologists,  and 
latterly  the  development  of  methods  for  measuring  blood-pressures 
directly  in  man.  The  Hales  method  of  measuring  arterial  pressure 
directly  in  terms  of  a  column  of  blood  is  inconvenient  on  account 
of  the  great  height,  large  fluctuations,  and  rapid  clotting.  The 
two  former  disadvantages  are  overcome  by  using  a  column  of  mer- 
cury. Since  this  metal  is  13.5  times  as  heavy  as  blood,  the  column 

*  For  an  account  of  the  life  and  works  of  this  physiologist  see  Dawson, 
"The  Johns  Hopkins  Hospital  Bulletin,"  vol.  xv,  Nos.  159  to  161,  1904. 
f  Poiseuille,  "Recherches  sur  la  force  du  coeur  aortique."    Paris,  1828. 
j  Ludwig,  "Miiller's  Archiv  f.  Anatomic,  Physiologic,  etc.,"  1847,  p.  242 


492 


CIRCULATION    OF    BLOOD    AND    LYMPH. 


which  will  be  supported  by  the  blood  will  be  correspondingly  shorter 
and  all  the  fluctuations  will  be  similarly  reduced.  Poiseuille 
placed  the  mercury  in  a  U  tube  of  the  general  form  shown  in  Fig. 
192,  M.  One  leg  was  connected  with  the  interior  of  an  artery  by 
appropriate  tubing  filled  with  liquid  and  when  the  clamp  was 
removed  from  the  vessel  its  pressure  displaced  the  mercury  in  the 
limbs  by  a  certain  amount.  The  difference  in  height  between  the 
levels  of  the  mercury  in  the  two  limbs  in  each  experiment  gives  the 
blood  pressure,  which  is  therefore  usually  expressed  as  being  equal 
to  so  many  millimeters  of  mercury.  By  this  expression  it  is  meant 
that  the  pressure  within  the  artery  is  able  to  support  a  column 


Fig.  192. — A,  Schema  to  show  the  recording  mercury  manometer  and  its  connection 
with  the  artery:  M,  The  manometer  with  the  position  of  the  mercury  represented  in  black 
(the  pressure  is  given  by  the  distance  in  millimeters  between  the  levels  1  and  2;  one-half  of 
this  distance  is  recorded  on  the  kymographion  by  the  pen,  P) ;  F,  the  float  resting  upon  the 
surface  of  the  mercury ;  G,  the  cap  through  which  the  stem  carrying  the  pen  moves;  E,  offset 
for  driving  air  out  of  the  manometer  and  for  filling  or  washing  out  the  tube  to  the  artery ; 
R,  the  receptacle  containing  the  soJution  of  sodium  carbonate ;  c,  the  cannula  for  insertion 
into  the  artery;  w,  the  washout  arrangement  shown  in  detail  in  B. 

B,  The  washout  cannula:  c,  the  glass  cannula  inserted  into  the  artery;  r,  the  stem 
connected  with  the  reservoir  of  carbonate  solution ;  o,  the  stem  connected  with  the  manom- 
eter. The  arrows  show  the  current  of  carbonate  solution  during  the  process  of  washing 
out,  the  artery  at  that  time  being  closed  by  a  clamp. 


of  mercury  that  many  millimeters  in  height,  and  by  multiplying 
this  value  by  13.5  the  pressure  can  be  obtained,  when  desirable, 
in  terms  of  a  column  of  blood  0?  water.  For  continuous  obser- 
vations and  permanent  records  the  height  of  the  column  of  mercury 
and  its  variations  during  an  experiment  are  recorded  by  the  device 
represented  in  Fig.  192. 


VELOCITY    AND    PRESSURE    OF    BLOOD-FLOW.  493 

The  distal  limb  of  the  U  tube  in  which  the  mercury  rises  carries  a  float 
of  hard  rubber,  aluminum,  or  some  other  substance  lighter  than  the  mercury. 
The  float  in  turn  bears  an  upright  steel  wire  which  at  the  end  of  the  glass  tube 
plays  through  a  small  opening  in  a  metal  or  glass  cap.  At  its  free  end  it  bears 
a  pen  to  trace  the  record.  If  smoked  paper  is  used  the  pen  is  simply  a  smooth- 
pointed  glass  or  metal  arm,  while  if  white  paper  is  employed  the  wire  carries 
a  small  glass  pen  with  a  capillary  tube,  which  writes  the  record  in  ink.  The 
tube  connecting  the  proximal  end  of  the  manometer  to  the  artery  of  the  ani- 
mal must  be  filled  with  a  solution  that  retards  the  coagulation  of  blood.  For 
this  purpose  one  employs  ordinarily  a  saturated  solution  of  sodium  carbonate 
and  bicarbonate  or  a  5  per  cent,  solution  of  sodium  citrate.  This  tube 
is  connected  also  by  a  T  piece  to  a  reservoir  containing  the  carbonate  solu- 
tion, and  by  varying  the  height  of  this  latter  the  pressure  in  the  tube  and 
the  manometer  may  be  adjusted  beforehand  to  the  pressure  that  is  sup- 
posed or  known  to  exist  in  the  artery  under  experiment.  By  this  means 
the  blood,  when  connections  are  made  with  the  manometer,  does  not  pen- 
etrate far  into  the  tube,  and  clotting  is  thereby  delayed.  In  long  obser- 
vations it  is  most  convenient  to  use  what  is  known  as  a  washout  cannula, 
the  structure  of  which  is  represented  in  Fig.  192,  B.  When  this  instru- 
ment is  attached  to  the  cannula  inserted  into  the  blood-vessel  one  can,  after 
first  clamping  off  the  artery,  wash  out  the  connections  between  the  artery 
and  the  manometer  with  fresh  carbonate  solution  as  often  as  desired.  By 
such  means  continuous  records  of  arterial  pressure  may  be  obtained  during 
many  hours.  Determinations  of  the  pressure  in  the  veins  may  be  made  with  a 
similar  apparatus,  but  owing  to  the  low  values  that  prevail  on  this  side  of 
the  circulation  it  is  more  convenient  to  use  some  form  of  water  manometer 
and  thus  record  the  venous  pressures  in  terms  of  the  height  of  the  water  column 
supported.  It  should  be  added  also  that  when  it  is  necessary  to  know  the 
pressure  in  any  special  artery  or  vein  the  connections  of  the  manometer  are 
made  usually  to  a  side  branch  opening  more  or  less  at  right  angles  into  the 
vessel  under  investigation,  or  if  this  is  not  possible  then  a  T  tube  is  inserted 
and  the  manometer  is  connected  with  the  side  branch.  The  reason  for  this 
procedure  is  that  if  the  artery  itselt  is  ligated  and  the  manometer  is  con- 
nected with  its  central  stump,  the  flow  in  it  and  its  dependent  system  of  capil- 
laries and  veins  is  cut  off;  the  stump  of  the  artery  constitutes  simply  a  con- 
tinuation of  the  tube  from  the  manometer  and  serves  as  a  side  connection 
to  the  intact  artery  from  which  it  arises.  Thus,  when  a  manometer  is  inserted 
into  the  carotid  artery  the  pressure  that  is  measured  is  the  side-pressure  in 
the  innominate  or  aorta  from  which  it  arises,  while  a  cannula  in  the  central 
stump  of  a  femoral  artery  measures  the  pressure  in  the  iliac.  A  specimen  of 
what  is  known  as  a  blood-pressure  record  is  shown  in  Fig.  193.  The  exact 
pressure  at  any  instant,  in  millimeters  of  mercury,  is  obtained  by  measuring 
the  distance  between  the  base  line  and  the  record  and  multiplying  by  2. 
The  base  line  represents  the  position  of  the  recording  pen  when  it  is  at  its 
zero  position  for  the  conditions  of  the  experiment.  It  is  necessary  to  multiply 
the  distance  between  the  base  line  and  the  record  by  2,  because,  as  is  seen  in 
Fig.  191,  the  recording  apparatus  measures  only  the  rise  of  the  mercury  in 
one  limb  of  the  manometer;  there  is,  of  course,  an  equal  fall  hi  the  other  limb. 

The  blood-pressure  record  (Fig.  193)  shows  usually  large  rhyth- 
mical variations  corresponding  to  the  respiratory  movements  and  in 
addition  smaller  waves  caused  by  the  heart  beat.  The  causes  of  the 
respiratory  waves  of  pressure  are  discussed  in  the  section  on  respi- 
ration. Regarding  the  heart  waves  or  pulse  waves  the  usual  record 
obtained  by  means  of  a  mercury  manometer  gives  an  entirely  false 
picture  of  the  extent  of  the  variations  in  pressure  caused  by  the  heart 
beat.  The  mass  of  mercury  possesses  considerable  weight  and  iner- 
tia, which  unfits  it  for  following  accurately  very  rapid  changes  in 
pressure.  When  the  pressure  changes  are  slow,  as  in  the  case  of 


494 


CIRCULATION    OF    BLOOD    AND    LYMPH. 


the  long  respiratory  waves  seen  in  the  record,  the  manometer  un- 
doubtedly indicates  their  extent  with  entire  accuracy.  But  when 
these  changes  are  very  rapid,  as  in  the  beat  of  a  dog's  or  rabbit's 
heart,  the  mercury  does  not  register  either  extreme  in  the  variation, 
but  tends  to  record  the  mean  or  average  pressure.  The  full  extent 
of  the  variations  in  arterial  pressure  caused  by  the  heart  beat  can  be 


Fig.  193. — Typical  blood  pressure  record  with  mercury  manometer:  Bp,  The  record 
showing  the  heart  beats  and  the  larger  curves  due  to  the  respirations  (respiratory  waves 
of  blood-pressure)  and  still  longer  waves  due  to  vasomotor  changes;  T,  the  time  line,  giving 
the  time  in  seconds.  The  actual  arterial  pressure  at  any  moment  is  the  distance  from  the 
base  line — that  is,  the  line  of  zero  pressure — to  the  blood-pressure  line,  multiplied  by  two. 
These  values  are  indicated  in  the  vertical  line  drawn  to  the  right,  which  shows  that  the 
average  pressure  at  the  time  of  the  experiment  was  100  mms.  Hg.  The  small  size  of  the 
variations  in  pressure  due  to  each  heart  beat  is  altogether  a  false  picture  due  to  the  inertia 
of  the  mercury,  its  inability  to  follow  completely  the  quick  change.  Each  heart  beat,  instead 
of  being  lower,  should  be  higher  than  the  respiratory  waves. 


determined  by  other  means  (see  below),  and,  if  the  knowledge  thus 
obtained  is  applied  to  the  correction  of  the  record  of  the  mercury 
manometer,  the  tracing  given  in  Fig.  193  should  have,  so  far  as  the 
heart  beats  are  concerned,  somewhat  the  appearance  shown  in  Fig. 
194.  This  latter  figure  gives  a  more  accurate  mental  picture  of 
the  actual  conditions  of  pressure  in  the  large  arteries,  as  influenced  by 


VELOCITY  AND  PRESSURE  OF  BLOOD-FLOW.  495 

the  heart  beat.  These  arteries  are,  in  fact,  subject  to  very  rapid  and 
very  extensive  changes  in  pressure  at  each  beat  of  the  heart,  and 
these  changes  are  naturally  more  pronounced  when  the  force  of  the 
heart  beat  is  increased, — for  instance,  1  y  muscular  exercise. 

Systolic,  Diastolic,  and  Mean  Arterial  Pressure. — As  stated 
in  the  last  paragraph,  the  arterial  pressure  in  the  larger  arteries 
undergoes  extensive  variations  with  each  heart  beat.  The  maxi- 
mum pressure  caused  by  the  systole  of  the  heart,  the  apex  of  the 
pulse  wave,  is  spoken  of  as  systolic  pressure;  the  minimum  pressure 
in  the  artery — that  is,  the  pressure  at  the  end  of  the  diastole  of  the 
heart,  or  the  bottom  of  the  pulse-wave,  is  known  as  the  diastolic 
pressure.  In  a  dog  under  ordinary  conditions  of  experimentation 
the  systolic  (lateral)  pressure  in  the  aorta  may  be  as  much  as  168 
mms.,  while  the  diastolic  pressure  is  only  100  mms.  In  man  the 


<£i/stolic  or  ma&ttnwm. 

HO  mm, 
95  to.**- 
SOJnm. 
.  {,0mm- 
Jtomm. 
.  ZOfnni- 

^             l\     A    A 

I  \j  \y  \ 

frtottfffttc  or  TntnirruMtt- 
£ase  line 

Fig.  194. — Schematic  representation  of  the  pressure  change  caused  by  each  heart 
beat.  The  schema  represents  three  heart  beats  supposed  to  be  recorded  on  a  rapidly  moving 
surface  by  a  manometer  delicate  enough  t9  follow  the  pressure  changes  accurately.  The 
top  of  the  pulse  wave  measures  the  systolic  pressure;  the  bottom  the  diastolic  pressure. 

systolic  pressure  as  measured  in  the  brachial  artery  may  be  taken 
in  round  numbers  as  equal  to  110  to  116  mms.,  while  the  diastolic 
pressure  is  only  65  to  75  mms.  The  difference  between  the 
systolic  and  the  diastolic  pressure  has  been  designated  con- 
veniently as  the  pulse  pressure.  It  measures,  of  course,  the 
variation  in  pressure  in  any  given  artery  caused  by  the  heart  beat, 
and  so  far  as  that  artery  is  concerned  it  gives  the  force  of  the 
heart  beat  except  for  the  small  component  used  to  accelerate 
the  movement  of  the  blood.  From  the  figures  given  above  it 
will  be  seen  that  the  pulse  pressure  in  the  brachial  artery  of 
man  averages  45  mms.  Hg.  Each  systole  of  the  'heart  distends 
this  artery,  therefore,  by  a  sudden  increase  in  pressure  equal 
to  the  weight  of  a  column  of  mercury  45  mms.  high.  As  we 
go  outward  in  the  arterial  tree  the  pulse  pressure  becomes  less 
and  less,  the  oscillations  in  pressure  with  each  heart  beat 
are  less  marked,  until,  finally,  in  the  smallest  arteries  and 


496 


CIRCULATION  OF  BLOOD  AND  LYMPH. 


capillaries  and  in  the  veins  there  is  no  pulse  wave,  and  no  difference 
between  systolic  and  diastolic  pressure.  In  speaking  of  the  pressure 
in  the  blood-vessels  we  refer  usually  to  what  is  called  the  mean 
pressure.  It  is  obvious  that,  so  far  as  the  larger  arteries  are  con- 
cerned, the  mean  pressure  is  only  a  convenient  expression  for  the 
average  pressure  during  a  certain  period.  If,  by  the  methods 
described  below,  we  determine  the  systolic  and  diastolic  pressures 
in  the  artery  of  a  man,  and  assume  that  there  has  been  no  general 
variation  between  the  two  observations,  we  can  estimate  the  mean 
pressure  with  approximate  accuracy  by  taking  the  arithmetical 
mean  of  the  two  figures,  or  by  adding  to  the  diastolic  pressure  one- 
half  of  the  pulse  pressure. 

The  arithmetical  mean  of  systolic  and  diastolic  pressures  during  any  given 
heart-beat  does  not  give  the  true  mean  pressure,  owing  to  the  form  of  the 
pulse  wave  (see  Fig.  214) .  If  the  rise  from  diastolic  to  systolic  pressure  and 
the  succeeding  fall  took  place  uniformly,  so  that  the  pulse  curve  constituted 


Fig.  195. — Schema  to  indicate  the  general  relations  of  systolic,  mean,  and  diastolie 
pressures  throughout  the  arterial  system:  «,  Systolic;  m,  mean;  d,  diastolic;  c,  pressure 
at  beginning  of  the  capillaries.  The  distance  from  8  to  d  represents  the  pulse  pressure  at 
different  parts  of  the  arterial  system. 


a  true  triangle,  the  true  mean  pressure  would  be  given  by  the  arithmetical 
mean  of  the  two  pressures.  As  a  matter  of  fact,  the  descending  limb 
of  the  pulse  curve  is  not  a  straight  but  a  curved  line,  and  it  is  broken, 
moreover,  by  secondary  waves.  The  position  of  the  mean  pressure  during 
any  given  heart-beat  will  vary,  therefore,  with  the  form  of  the  pulse  curve. 
Generally  speaking,  it  lies  nearer  to  the  diastolic  than  to  the  systolic  level.* 

In  physiological  observations,  as  a  rule,  no  attempt  is  made  to 
estimate  the  mean  pressure  for  any  given  time  with  mathematical 
accuracy.  In  the  ordinaiy  tracing  as  given  by  the  mercury  man- 
ometer (Fig.  193)  the  mean  pressure  for  any  given  period  during 
which  the  variations  have  been  symmetrical  and  not  extreme  is 
estimated  as  the  arithmetical  mean  of  the  highest  and  lowest 
points  reached.  When  desirable,  the  mean  pressure  may  be 
recorded  by  introducing  a  resistance  (narrowing  the  tube  by  means 
of  a  stopcock)  between  the  artery  and  the  manometer.  The  latter 
*  See  Dawson,  "British  Medical  Journal,"  1906,  996. 


VELOCITY  AND   PRESSURE  OF  BLOOD-FLOW. 


497 


Fig.  196. — Diagram  showing  construction  of  Hurthle's  manometer. — (After  Curtis.) 
The  interior  of  the  heart  or  the  artery  is  connected  by  rigid  tubing  to  a  very  small  tambour, 
T.  The  tubing  and  the  tambour  are  filled  with  liquid.  The  movements  of  the  rubber  dam 
covering  the  tambour  are  greatly  magnified  by  a  compound  lever,  S.  t  The  tendency  of  this 
lever  to  "fling"  may  be  prevented  by  an  arrangement  not  shown  in  the  diagram.  The 
essential  principles  of  the  recorder  are,  first,  liquid  conduction  from  heart  to  tambour; 
second,  a  very  small  tambour  and  membrane  so  that  a  minimal  volume  of  liquid  escapes 
from  the  heart  into  the  tambour. 


will  then  record  mean  pressure  and  show  no  variations 
with  the  heart-beat.  A  general  idea  of  the  variations  in 
systolic,  diastolic,  and  mean  pressures,  throughout  the 
arterial  system,  may  be  obtained  from  the  schema  given 
in  Fig.  195. 

Method  of  Measuring  Systolic  and  Diastolic  Pres- 
sure in  Animals. — In  animals  a  manometer  may  be  con- 
nected directly  with  the  artery  and  systolic  and  diastolic 
pressures  may  be  obtained  in  one  of  two  general  ways: 
(1)  By  using  some  form  of  pressure  recorder  or  manom- 
eter sufficiently  mobile  to  follow  very  quick  changes  of 


To  the  artery. 


Fig.  197. — Schema  to  illustrate  the  use  of  valves  in  determining  maximum  (systolic) 
and  minimum  (diastolic)  blood-pressure.  When  stopcock  a  is  open  the  heart  beats  are 
transmitted  through  the  maximum  valve  and  the  mercury  in  the  manometer  is  prevented 
from  falling  between  beats.  The  manometer  will  record  the  highest  pressure  reached  during 
the  period  of  observation.  The  reverse  occurs  when  valve  6  alone  is  open. 

32 


498 


CIRCULATION    OF    BLOOD    AND    LYMPH. 


pressure.  (2)  By  using  a  mercury  manometer  provided  with 
maximum  and  minimum  valves.  Of  the  manometers  that  have 
been  devised  to  register  the  quick  changes  in  pressure  exhibited 
in  the  cavity  of  the  heart  itself,  or  in  the  pulsations  of  the  arteries 
due  to  the  heart-beat,  the  ones  that  have  given  the  most  accurate 
results  are  the  membrane-manometer  of  Htirthle  and  the  optical 
manometers  which  depend  upon  the  use  of  the  segment-capsule 
devised  by  Frank. 

The  principle  made  use  of  in  the  Hurthle  manometer  is  illustrated 
by  the  diagram  in  Fig.  196.  The  instrument  consists  essentially  of  a  small 
box  or  tambour  of  very  limited  capacity;  the  top  of  the  tambour  is  covered 
with  thin  rubber  dam  and  the  cavity  is  filled  with  liquid  and  connected  by 
rigid  tubing,  also  filled  with  liquid,  with  the  interior  of  the  artery  or  heart. 
Variations  in  pressure  in  the  artery  are  transmitted  through  the  column  of 
liquid  to  the  rubber  membrane  of  the  tambour,  and  the  movements  of  this 
latter  are  greatly  magnified  by  a  sensitive  lever  attached  to  it.  The  liquid 
conduction  and  the  small  size  of  the  tambour,  which  prevents  any  notice- 
able outflow  of  liquid,  combine  to  make  a  sensitive  and  very  prompt  recorder 
of  pressure  changes.  It  is  necessary  to  calibrate  this  instrument  whenever 
used  in  order  to  give  absolute  values  to  the  records  obtained.  A  specimen 


Fig.  198.— Blood-pressure  record  from  a  dog  with  a  Hurthle  manometer.  The  size 
of  the  heart  beats  is  relatively  much  greater  than  with  a  mercury  manometer.  In  this  case 
the  systolic  pressure  is  about  150  mms.  Hg;  the  diastolic,  100  mms.;  and  the  heart  beat  or 
pulse  pressure,  50  mms. 

Plate 


A  B 

Fig.  198a.— A,  The  segment  capsule.  One  side  of  a  recording  tambour  is  flattened  so  that 
a  segment  is  cut  off.  Thin  rubber-dam  is  stretched  over  the  capsule.  A  small  trapezoidal  piece 
of  thin  celluloid  (c)  is  cemented  to  the  rubber,  so  that  its  broad  side  pivots  on  the  chord  side 
of  the  circle.  On  this,  in  turn,  is  cemented  a  small  mirror  (m) ,  so  that  its  diameter  also  pivots 
on  the  chord  side  of  the  circle. 

B,  Diagram  to  show  the  band  of  light  reflected  from  the  mirror  of  the  segment  capsule  to 
a  photographic  plate.  In  this  way  a  photographic  record  is  obtained  of  the  movements  of  the 
mirror  caused  by  the  pressure  changes  transmitted  to  the  segment-capsule.— (From  Wiggers.) 

of  a  blood-pressure  record  obtained  with  this  instrument  is  shown  in  Fig.  198. 
It  will  be  noticed  that  the  size  of  the  heart-beat,  relative  to  the  distance  from 


VELOCITY    AND    PRESSURE    OF    BLOOD-FLOW. 


499 


the  base  line,  is  much  greater  than  in  the  record  obtained  with  the  mercury 
manometer,  Fig.  193. 

In  the  optical  manometers  the  errors  due  to  the  mass  and  friction  of  levers 
are  avoided  by  making  use  of  a  beam  of  light  which  is  reflected  from  a  small 
mirror  attached  to  a  segment-capsule.  The  construction  of  the  segment-cap- 


S\> 


C-M 


190 


too 


L<L 


Fig.  199. — Curve  showing  the  results  of  actual  measurement  of  systolic,  diastolic,  and 
mean  pressure  (lateral  pressures)  along  the  a9rta  and  femoral  of  the  dog.  The  branches 
through  which  the  lateral  pressures  were  obtained  are  indicated  as  follows:  Sb,  Left  sub- 
clavian ;  C-M,  celiac  and  superior  mesenteric ;  R,  left  renal ;  F,  left  femoral  (Ellenberger 
and  Baum),  external  iliac;  P,  profunda  branch  of  femoral;  S,  saphena.  The  pressure  in 
millimeters  is  given  along  the  ordinates  to  the  left.  It  will  be  noted  that  the  mean  and 
the  diastolic  pressures  remain  practically  the  same  through9Ut  the  descending  aorta  and 
into  the  femoral.  The  systolic  pressure  shows  a  marked  increase  at  the  lower  end  of 
the  aorta  and  then  falls  off  rapidly.  The  pulse  pressure  at  the  inferior  end  of  the  descend- 
ing aorta  is  much  larger  than  at  the  arch. — (Dawson.) 

eule  and  a  diagram  of  the  optical  method  of  using  it  are  shown  in  Fig.  198a.* 

The  method  that  depends  upon  the  use  of  maximum  and  minimum  valves 
may  be  understood  by  reference  to  Fig.  197.  On  the  path  between  the  artery 

*  See  Wiggers, "  Modern  Aspects  of  the  Circulation  in  Health  and  Disease," 
1915;  also  "Journal  of  the  American  Medical  Association,"  April  17,  1915. 


500  CIRCULATION    OF    BLOOD   AND    LYMPH. 

and  the  manometer  one  may  place  a  maximum  and  a  minimum  valve  so  ar- 
ranged that  the  blood-pressure  and  heart  beat  may  be  transmitted  through 
either  valve.  As  is  shown  by  the  figure,  if  the  connection  is  maintained 
through  the  maximum  valve  for  a  certain  time  the  highest  pressure  reached 
during  that  period  will  be  recorded,  while,  when  the  minimum  valve  is  used 
the  lowest  pressure  reached  will  be  indicated. 

Such  valves,  of  course,  act  slowly  and  can  not  be  used  to  determine  the 
maximum  and  minimum  pressure  in  the  artery  during  a  single  heart  beat' 
they  record  the  highest  and  lowest  point  reached  during  a  certain  given 
interval. 

Actual  Data  as  to  the  Mean  Pressure  in  Arteries,  Veins, 
and  Capillaries. — The  mean  value  of  the  pressure  in  the  aorta 
has  been  determined  for  many  mammals.  It  is  fpund  that  the  artuaJ 
figures  vary  with  the  conditions  under  which  the  results  have  been 
obtained.  Such  values  as  the  following  may  be  quoted:* 

Horse 321  mms.  to  150  mms.  Hg. 

Dog 172  "  104      "       " 

Sheep 206  "  156      "       " 

Cat 150 


Rabbit 108 

Man  (probable,  Tigerstedt) 150 


90 


It  appears  from  these  figures  that  there  is  no  proportion  between 
the  size  of  an  animal  and  the  amount  of  mean  arterial  pressure.  It 
is  probable  that  there  may  be  a  general  relationship  between  the 
size  of  the  animal — that  is,  the  size  of  the  heart — and  the  amount 
of  pulse  pressure  or  the  oscillation  of  pressure  with  each  heart  beat, 
but  sufficient  data  are  not  at  hand  to  determine  this  point.  As 
we  pass  from  the  aorta  to  the  smaller  arteries  the  mean  pressure 
decreases  somewhat,  although  not  very  rapidly,  while  the  pulse 
pressure  decreases  also  and  to  a  more  noticeable  extent. 

This  fact  is  illustrated  in  Fig.  199,  which  gives  a  graphic 
representation  of  a  number  of  experimental  determinations f  of. 
systolic  and  diastolic  pressures  in  the  large  arteries  of  the  dog. 

If  we  turn  to  the  other  end  of  the  vascular  system,  the  veins, 
we  find  that  the  lowest  pressure  is  in  the  venae  cavae  and  that  it 
increases  gradually  as  we  go  toward  the  capillary  area.  Accord- 
ing to  one  observer,  {  the  fall  in  pressure  from  periphery  toward 
the  heart  is  at  the  rate  of  1  mm.  Hg  for  every  35  mms.  of  distance. 
We  have  such  figures  as  the  following: 

DOG  (OPITZ).  SHEEP. 

Superior  vena  cava  (near  Jugular  vein 0.2  mm.    Hg. 

auricle) =  —2.96  mms.  Hg.        Facial  vein 3.0  mms.   " 

Superior  vena  cava  more  Branch  of  brachial    ...    9.0 


distal =  —1.38 

External  jugular  (left)  .   .  =      0.52  mm. 

Right  brachial =      3.90  mms. 

Left  facial =      5.12      " 

Left  femoral =      5.39      ' 

Left  saphenous     .   .   .   .   .  =      7.42     " 


Crural 11.4 


*  See  Volkmann.  "Die  Haemodynamik,"  1850. 

t  Dawson,  "American  Journal  of  Physiology,"  9,  198,  1903. 

j  Burton-Opitz,  "American  Journal  of  Physiology,"  9,  198,  1903. 


VELOCITY    AND    PRESSURE    OF    BLOOD-FLOW.  501 

At  the  heart,  therefore,  the  pressure  of  the  blood  upon  the  walls 
of  the  veins  is  very  small,  and,  indeed,  owing  to  the  circumstance 
that  the  large  veins  lie  in  the  thoracic  cavity,  in  which  the  pres- 
sure is  below  that  of  the  atmosphere,  the  pressure  of  the  blood  in 
them  may  also  be  below  atmospheric  pressure,  although  doubt- 
less at  this  point  (vena  cava)  the  pressure  within  the  vein  is 
greater  than  the  pressure  on  its  exterior  (intrathoracic  pressure). 
Taking  into  account  the  negative  intrathoracic  pressure  (p.  662) 
it  may  be  estimated  that  the  difference  in  pressure  between  the 
blood  in  the  veins  of  the  neck  and  that  in  the  superior  vena  cava 
is  equal  to  4  or  5  mms.  Hg.,  and  this  difference  is  sufficient  to  drive 
the  blood  into  the  heart  and  to  fill  and  distend  it  rapidly  during 
diastole*  To  complete  the  general  conception  of  the  pressure 
relations  in  the  vascular  system  it  is  necessary  to  know  the  pressure 
of  the  blood  in  the  smallest  arteries  and  veins  and  in  the  capillaries. 


Fig.  200.— Schematic  representation  of  the  general  relations  of  blood-pressure  (side 
pressure)  in  different  parts  of  the  vascular  system:  a,  The  arteries;  c,  the  capillaries;  v, 
the  veins.  The  mean  and  diastolic  pressures  remain  nearly  constant  in  the  arterial  system, 
as  far  as  they  can  be  measured  accurately.  The  pressures  in  the  veins  are  represented  as 
uniform  at  any  one  point.  In  the  large  veins  near  the  heart  there  are  variations  of  pressure 
with  each  respiration  and  with  each  heart  beat  (Venous  Pulse,  p.  532\ 

It  is  not  possible — in  the  cases  of  the  capillaries,  for  instance — to 
connect  a  manometer  directly  with  the  vessels,  and  recourse  has 
been  had  to  a  less  direct  and  certain  method.  The  pressure  in  the 
capillaries  in  different  regions  of  the  skin  has  been  estimated  by 
determining  the  pressure  necessary  to  obliterate  them — that  is,  to 
blanch  the  skin.  A  glass  plate  is  laid  upon  the  skin  or  mucous 
membrane  and  weights  are  added  until  a  distinct  change  in  the 
color  of  the  skin  is  noted  f  Knowing  the  necessary  weight  to  pro- 
duce this  effect  and  the  area  submitted  to  compression,  the  pressure 
may  be  expressed  in  terms  of  millimeters  of  mercury  or  blood. 

The  following  example  may  be  used  to  illustrate  this  method.  Suppose 
that  the  glass  plate  has  an  area  of  4  sq.mms.,  and  that  to  blaneh  the  skin  under 
it  a  weight  of  1  gm.  is  necessary;  1  gm.  of  water  =  1  c.c.  or  1000  c.  mms.1 

*  Henderson  and  Barringer,  "Amer.  Journal  of  Physiology/'  31,  352,  1913. 
t  V.  Kries  "Berichte  d.  Sachs.  Gesellschaft  d.  Wiss.  Math.-phys.  Classe  " 
1875,  p.  138. 


502 


CIRCULATION    OF    BLOOD    AND    LYMPH. 


Therefore  to  blanch  this  area  would  require  a  column  of  water  contain- 
ing 1000  c.mms.  with  a  cross-area  of  4  sq.mms.  The  height  of  this  column 
would  therefore  be  equal  to  ^^  or  250  mms.  of  water, — that  is,  18.5  mms. 
Hg. 

The  results  obtained  by  this  method  are  not  very  constant  and 
can  only  be  considered  as  approximate.  It  would  appear,  how- 
ever, that  the  pressure  lies  somewhere  between  20  and  40  mms. 
of  mercury.  Thus,  upon  the  gums  of  a  rabbit  von  Kries  found  a 
capillary  pressure  of  33  mms.  Hg. 

By  means  of  a  more  adjustable  instrument  von  Reckling- 
hausenf  estimates  that  in  man  the  pressure  within  the  capil- 
laries of  the  finger-tips  or,  to  be  more  accurate,  within  the  small 
arteries  supplying  these  capillaries,  is  equal  to  55  mms.  Hg. 
(See  p.  510.) 

The  general  relations  of  the  pressures  in  arteries,  veins,  and 
capillaries  may  be  expressed  in  a  curve  such  as  is  shown  in  Fig. 
200. 

It  should  be  added  that  in  this  curve  and  in  all  the  figures 
so  far  quoted  in  regard  to  the  actual  pressure  within  the  different 


d 


Fig.  201. — Figure  of  the  Riva-Rocci  apparatus  (Sahl-i) :  a,  The  leather  collar  with 
inside  rubber  bag  to  go  on  the  arm ;  c,  the  bulb  for  blowing  up  the  rubber  bag  and  thus 
compressing  the  artery;  d,  the  manometer  dipping  into  the  reservoir  of  mercury,  6,  to  meas- 
sure  the  amount  of  pressure. 

arteries  and  veins,  it  is  assumed  that  the  animal  is  in  a  recumbent 
posture.  In  an  animal  standing  upon  his  feet,  especially  in  an 
upright  animal  like  man,  it  is  obvious  that  the  effect  of  gravity 
will  modify  greatly  the  actual  figures  of  pressure.  Upon  the  arte- 
ries and  veins  of  the  feet,  for  example,  there  will  be  exerted  a 
*  Von  Recklinghausen,  "Archiv  f.  exp.  Path.  u.  Pharmak.,"  55,  375,  1907. 


VELOCITY    AND    PRESSURE    OF    BLOOD-FLOW.  503 

hydrostatic  pressure  equal  to  the  height  of  the  column  of  liquid 
between  the  feet  and  the  heart,  which  adds  itself  to  the  pressure 
resulting  from  the  circulation  as  caused  by  the  heart.  When  the 
animal  is  in  a  recumbent  position  the  hydrostatic  factor  practi- 
cally disappears.  (See  p.  518.) 

The  Method  of  Determining  Blood-pressure  in  the  Largd 
Arteries  of  Man. — It  is  a  matter  of  interest  and  practical  impor- 
tance to  ascertain  even  approximately  the  arterial  pressure  in  mail 
and  its  variations  in  health  and  disease.  The  first  practical  method 
for  determining  this  point  upon  man  was  suggested  by  von  Basch 
(1887),  who  devised  an  instrument  for  this  purpose,  the  sphygmo- 
manometer.  Since  that  time  a  number  of  different  instruments 
have  been  described,  but  attention  may  be  called  to  two  only,  which 
illustrate  sufficiently  well  the  principles  involved.  In  the  first 
place,  it  must  be  clearly  recognized  that  the  arterial  pressure  in 
the  large  arteries  of  man  shows  marked  variations  with  the  heart 
beat;  the  pressure  during  the  beat  of  the  heart  rises  suddenly 
to  a  much  higher  level  than  during  the  diastole.  The  relation  of 
the  systolic  (or  maximum)  and  diastolic  (or  minimum)  pressures 
is  indicated  by  the  diagram  in  Fig.  195.  The  instruments  that 
have  been  invented  for  determining  human  blood-pressure  are  in 
reality  adapted,  more  or  less  accurately,  to  determine  one  or  the 
other  or  both  of  these  pressures.  No  instrument  has  been  devised 
for  determining  the  mean  pressure,  and  as  a  matter  of  fact  such 
a  thing  as  mean  pressure  does  not  exist  in  the  large  arteries,  it  is 
simply  an  abstraction.  What  really  occurs  in  these  arteries  is  a 
rapid  swing  of  pressure  with  each  heart-beat  from  the  diastolic 
to  the  systolic  level,  and  to  interpret  fully  our  records  it  is  impor- 
tant to  determine  each  of  these  values.  The  methods  that  have 
been  proposed  for  this  purpose  have  undergone  a  gradual  evolu- 
tion and  improvement.  The  determinations  of  systolic  pressure 
were  first  made,  according  to  the  principle  suggested  by  von  Basch, 
by  ascertaining  the  pressure  that  is  just  sufficient  to  occlude  an 
artery,  so  that  a  pulse  wave  cannot  pass  through.  The  simplest 
form  of  apparatus  for  this  purpose  is  the  one  proposed  by  Riva- 
Rocci  and  represented  in  Fig.  201.  Instruments  of  this  kind  are 
known  as  sphygmomanometers. 

The  leather  or  canvas  band,  a,  is  buckled  snugly  around  the  arm.  On 
the  inner  surface  of  this  band  there  is  a  rubber  bag  which  communicates  with 
the  mercury  manometer,  d,  and  the  pressure  bulb,  c.  When  the  band  is  in 
place  rhythmical  compressions  of  c  will  force  air  into  the  rubber  bag  surround- 
ing the  arm.  This  bag  is  blown  up  and  exerts  pressure  upon  the  arm  and 
through  the  arm  tissue  upon  the  brachial  artery.  The  amount  of  pressure 
that  is  being  exerted  upon  the  arm  is  indicated  at  any  moment  by  the  mer- 
cury manometer.  The  moment  of  obliteration  of  the  artery  is  determined 
by  feeling  (or  recording)  the  pulse  in  the  radial  artery.  The  moment  that 
this  pulse  disappears,  as  the  pressure  upon  the  brachial  is  raised,  indicates  the 
maximum  or  systolic  pressure  in  the  brachial  artery.  As  the  pressure  is  low- 


504  CIRCULATION    OF    BLOOD    AND    LYMPH. 

ered  again  the  pulse  reappears.  Among  other  sources  of  error  involved  in 
this  method  it  is  to  be  remembered  that  trie  tactile  sensibility  is  not  sufficiently 
delicate  to  detect  a  minimal  pulse  in  the  artery.  Other  methods  of  determin- 
ing the  systolic  pressure  (see  below)  indicate,  as  a  matter  of  fact,  that  the 
pulse  continues  some  time  after  an  individual  of  average  tactile  sensibility  is 
unable  to  detect  it. 

For  practical  purposes,  a  great  improvement  was  made  by 
Korotkoff  in  the  introduction  of  the  auscultation  method  by  means 
of  which  both  systolic  and  diastolic  pressures  may  be  determined 
rapidly  with  approximate  accuracy.  In  this  method  the  cuff 
with  its  pneumatic  bag  (a)  is  placed  round  the  arm  above  the  elbow, 
and  by  means  of  a  bulb  (c)  or  pump  the  pressure  within  the  pneu- 
matic bag  is  raised  until  the  brachial  artery  is  completely  obliter- 
ated. A  stethoscope  is  now  applied  to  the  location  of  the  brachial 
artery  just  below  the  lower  edge  of  the  cuff,  and  by  means  of  a 
needle  valve  the  pressure  on  the  artery  is  allowed  to  drop  slowly. 
The  moment  that  the  pressure  falls  to  a  point  at  which  a  pulse 
wave  can  break  through  the  constricted  area  a  distinct  sound 
will  be  heard  in  the  stethoscope.  If  the  mercury  manometer  is 
read  at  this  point,  it  will  give  the  value  for  the  systolic  pressure. 
As  the  outside  pressure  continues  to  fall  the  sound  alters  in  char- 
acter. According  to  the  description  of  Ettinger*  it  passes  through 
five  phases:  1,  The  initial  sharp  clear  sound;  2,  muffled  with  the 
character  of  a  murmur;  3,  clear  and  loud;  4,  dull;  5,  cessation. 
Some  observers  have  thought  that  the  fifth  phase,  the  cessation  of 
the  sound,  marks  the  point  of  minimal  or  diastolic  pressure,  but 
later  workers  seem  to  agree  that  this  pressure  is  indicated  more 
accurately  by  the  transition  from  phase  3  to  phase  4,  at  the  begin- 
ning of  phase  4.  The  difference  in  pressure  between  this  point 
and  that  at  which  the  sound  disappears  may  be  slight  ordinarily, 
but  in  some  cases  may  be  considerable.!  If,  however,  for  any 
reason  it  is  desirable  to  obtain  a  record  of  the  systolic  and  dias- 
tolic pressures,  some  form  of  sphygmomanometer  must  be  employed 
in  which  the  pulse  from  the  artery  under  the  cuff  is  recorded  upon 
the  smoked  surface  of  a  kymographion.  Several  instruments  of 
this  kind  have  been  described,  but  the  one  devised  by  ErlangerJ 
is  probably  the  most  complete.  This  instrument  is  illustrated  in 
Figs.  203  and  204,  and  is  described  in  some  detail  below.  When 
the  pressure  in  the  cuff  is  raised  above  the  systolic  level  the  brachial 
artery  is  completely  closed,  but  the  pulsations  of  the  stump  above 

*  Ettinger,  "Weiner  Klin.  Wochenschrift,"  20,  992,  1907. 

t  Weysse  and  Lutz,  "American  Journal  of  Physiology,"  32,  427,  1913;  and 
Melvin  and  Murray,  "Quarterly  Journal  of  Experimental  Physiology,"  8,  125, 
1914. 

t" American  Journal  of  Physiology,"  "Proceedings  of  the  American 
Physiological  Society,"  6,  xxii.,  1902;  and  "Johns  Hopkins  Hospital  Reports," 
12,  53,  1904. 


VELOCITY    AND    PRESSURE    OF    BLOOD-FLOW. 


505 


the  closed  area  are  recorded  through  the  tambour  system  connected 
with  the  cuff.  By  means  of  a  suitable  stop-cock  the  pressure  in 
the  cuff  is  dropped,  5  mms.  at  a  time,  and  a  record  of  the  pulse  is 


Fig  202. — Rec9rd  (Erlanger)  to  show  the  maximum  size  of  the  recorded  pulse 
wave  when  the  outside  or  extravascular  pressure  is  equal  to  the  internal  diastolic  pressure. 
Ine  artery  is  compressed  first  with  a  pressure  above  systolic,  sufficient  to  obliterate  the 
lumen.  As  this  pressure  is  lowered  in  steps  of  5  mms.  the  recorded  pulse  wave  increases  in 
size  to  a  maximum  and  then  again  becomes  smaller.  The  outside  pressure  with  which  the 
maximum  pulse  is  obtained  measures  the  amount  of  the  internal  diastolic  pressure  (Marey*s 

taken  at  each  level.  The  point  of  systolic  pressure  is  indicated 
either  by  a  sudden  increase  in  the  size  of  the  pulse  or  by  a  sudden 
spreading  of  the  limbs  of  the  pulse  wave.  As  the  pressure  is 


Fig.  203. — Schema  showing  the  construction  of  the  Erlanger  apparatus:  a,  Rubber 
bag  of  the  arm  piece ;  c,  bulb  for  blowing  up  this  bag  and  putting  pressure  on  the  arm ;  6, 
the  manometer  for  measuring  the  pressure;  i,  two-way  stopcock  (when  turned  so  as  to 
communicate  with  the  capillary  opening,  k,  it  allows  the  pressure  in  a  to  fall  slowly) ;  e, 
a  rubber  bag  in  a  glass  chamber,  /;  e  communicates  with  a  when  stopcock  d  is  open _ and 
the  pulse  waves  from  a  are  transmitted  to  e;  the  pulsations  of  e  in  turn  are  transmitted 
k>  the  delicate  tambour,  h,  and  are  thus  recorded. 

dropped  in  steps  below  this  point  the  size  of  the  pulse  wave  in- 
creases to  a  maximum,  and  then  again  declines  (Fig.  202).  The 
pressure  at  which  the  maximum  pulse  waves  are  obtained  or  (Er- 
langer) the  first  decrease  in  the  size  of  the  waves  indicates  diastolic 


506 


CIRCULATION    OF    BLOOD    AND    LYMPH. 


pressure,  according  to  the  principle  first  suggested  by  Marey.  This 
principle  assumes  that  when  the  pressure  on  the  outside  of  an  artery 
is  just  equal  to  the  diastolic  pressure  on  the  inside,  that  is  to  say,  to 
the  pressure  in  between  the  pulse  beats,  the  arterial  wall  is  in  a  posi- 
tion in  which  it  will  give  the  widest  excursion  for  any  given  force  of 
heart  beat.  The  correctness  of  this  principle  has  been  demonstrated 
upon  the  exposed  artery.  In  the  living  person  a  certain  amount 
of  soft  compressible  tissue  intervenes  between  the  cuff  and  the 


Fig.  204. — Erlanger  apparatus.     The  collar  for  the  arm  is  not  shown.     The  parts  may  be 
understood  by  reference  to  the  schema  given  in  Fig.  203. 

brachial  artery,  and  a  portion  of  the  external  pressure  is  used  in 
overcoming  the  resistance  of  this  tissue.  The  readings  as  made 
are,  therefore,  probably  somewhat  above  the  actual  diastolic  pres- 
sure by  an  amount  that  has  been  estimated  at  from  6  to  10  mms. 
of  mercury.  As  these  instruments  are  usually  employed,  measure- 
ments are  made  upon  the  brachial  artery  at  the  level  of  the  heart, 
and  consequently  no  correction  need  be  made  for  a  hydrostatic 


VELOCITY    AND    PRESSURE    OF    BLOOD-FLOW.  507 

factor,  such  as  would  be  necessary,  for  example,  if  the  determi- 
nations were  made  on  an  artery  in  the  leg  in  a  person  standing 
erect. 

The  way  in  which  the  Erlanger  apparatus  is  used  may  be  understood  from 
the  schematic  Fig.  203.  a  is  the  rubber  bag,  which  is  buckled  upon  the  arm 
by  a  leather  strap.  This  bag  communicates  with  the  mercury  manometer,  b, 
with  a  pressure  bag,  c,  through  the  two-way  stopcock,  i,  and  through  the 
stopcock  d  with  a  rubber  bag,  e,  contained  in  a  glass  chamber,  .f.  This  glass 


Fig.  205. — To  show  the  method  of  detecting  the  systolic  pressure  upon  the  tracing  given 
by  the  Erlanger  sphygmomanometer.  The  pressure  upon  the  arm  is  raised  above  systolic 
pressure  and  is  then  dropped  5  mm.  at  a  time,  a  short  record  being  taken  after  each  drop. 
Records  are  shown  for  130,  125,  120,  115,  and  110  mm.  At  115  mm.  it  will  be  seen  that 
the  limbs  of  the  pulse-wave  show  the  separation  or  spreading  which  indicates  the  first  pulse- 
wave  to  get  through  the  occluded  artery,  and  therefore  the  systolic  pressure. 

chamber  communicates  above  with  a  sensitive  tambour,  h,  and  by  means  of  the 
stopcock  g  can  be  placed  in  communication  with  the  outside  air.  The  systolic 
pressure  may  be  determined  in  two  ways:  By  one  method  only  the  mercury 
manometer  is  necessary,  the  instrument  corresponding  with  the  Riva-Rocci 
apparatus  described  above.  By  means  of  the  pressure  bag,  c,  the  bag,  a,  up 
the  arm  is  blown  up  until  the  pressure  is  above  the  systolic  pressure  and  the 
radial  pulse  below  disappears.  By  turning  stopcock  i  properly  the  system  is 
allowed  to  communicate  with  the  air  through  a  capillary  opening,  k.  Conse- 
quently the  pressure  upon  the  artery  in  the  arm  falls  slowly,  and  by  palpating 
the  radial  artery  one  can  determine  the  pressure,  as  measured  by  the  mercury 
manometer,  at  which  the  pulse  just  gets  through.  This  pressure  will  measure 
approximately  the  systolic  pressure.  The  second  method  (method  of  v. 
Recklinghausen)  gives  higher  and  doubtless  more  accurate  results.  In  this 
method  the  pressure  is  at  first  raised  above  systolic  pressure  with  stopcocks 
d  and  g  open,  a,  e,  and  b  are  under  the  same  pressure.  If  stopcock  g  is  now 
turned  off,  the  pulsations  in  a  are  transmitted  to  e  and  through  it  to  the 
tambour,  h,  and  the  lever  of  the  tambour  writes  these  pulsations  on  a  kymo- 
graphion.  It  should  be  explained  that  pulsations  are  obtained  even  when 
the  pressure  on  the  arm  is  much  more  than  sufficient  to  completely  obliterate 
the  brachial  artery.  The  reason  for  this  is  that  the  pulsations  of  the  central 
stump  of  the  closed  artery  will  be  communicated  to  bag  a.  When  the  pressure 
is  suprasystolic  these  pulsations  are  small.  If  now  the  pressure  in  the  system 
is  diminished  slowly  by  turning  stopcock  i  so  as  to  communicate  with  the 
capillary  opening,  k,  it  will  be  found  that  at  a  certain  point  the  pulsations 
suddenly  increase  in  height  (Fig.  205) .  This  point  marks  the  moment  when 
the  pulse  wave  is  first  able  to  break  through  the  brachial  artery,  and  it  gives, 
therefore,  the  systolic  pressure.  In  many  cases  this  method  of  determining 


508  CIRCULATION    OF    BLOOD    AND    LYMPH. 

the  point  of  systolic  pressure  is  not  satisfactory,  since  the  pulse  waves  increase 
gradually  in  amplitude  without  a  sudden  break,  or  perhaps  there  is  more 
than  one  place  at  which  a  sudden  increase  occurs.  A  more  reliable  method 
according  to  Erlanger  is  to  note  the  point  at  which  the  ascending  and  descend- 
ing limbs  of  the  pulse  wave  show  a  noticeable  separation  (Fig.  205).  "At 
the  moment  the  pressure  on  the  artery  falls  below  systolic,  blood  succeeds  in 
making  its  way  beneath  the  cuff.  This  must  be  squeezed  out  before  the  lever 
can  return  to  the  base  line,  whereas  at  higher  pressures  the  lever  is  raised 
only  through  the  hydraulic-ram  action  of  the  pulse  wave  upon  the  upper 
edge  of  the  cuff."  After  finding  the  systolic  pressure  the  diastolic  pressure 
is  obtained  by  allowing  the  pressure  to  drop  still  further.  The  pulsations 
increase  in  height  to  a  maximum  size  and  then  decrease.  The  pressure  at 
which  the  maximum  pulse  wave  is  obtained  marks  the  diastolic  pressure. 
It  is  better  perhaps  in  dropping  the  pressure  for  this  last  purpose  to  manipu- 
late stopcock  i  so  as  to  drop  the  pressure  5  mms.  at  a  time,  recording  the  pulse 
wave  at  each  pressure.  In  this  way  a  record  is  obtained  such  as  is  given  in 
Fig.  202.  It  should  be  added,  also,  that  in  order  to  keep  the  lever  of  the 
tambour  horizontal  while  the  pressure  in  the  system  is  being  lowered  there 
is  a  minute  pinhole  in  the  metal  bottom  of  the  tambour.  Through  this 
pinhole  the  pressure  in  the  tambour  and  chamber,  /,  is  kept  atmospheric 
throughout,  except  during  the  quick  changes  caused  by  the  pulse  waves. 
By  means  of  this  instrument  one  can  determine  within  a  minute  or  so  the 
amount  of  the  systolic  and  diastolic  pressure  in  the  brachial  artery,  and  also, 
of  course,  the  difference  between  the  two,  the  pulse  pressure,  which  may  be 
taken  as  an  indication  of  the  force  of  the  heart-beat. 

The  Normal  Arterial  Pressure  in  Man  and  Its  Variations.— 
By  means  of  one  or  other  of  the  instruments  devised  for  the 
purpose,  numerous  results  have  been  obtained  regarding  the 
blood-pressure  in  man  at  different  ages  and  under  varying  normal 
and  abnormal  conditions.  Unfortunately,  the  methods  used  have 
not  always  been  complete.  Some  authors  give  only  systolic 
pressures,  for  example.  In  such  experiments  also  a  troublesome 
factor  is  always  the  psychical  element.  The  mental  interest 
that  the  individual  experimented  upon  takes  in  the  procedure 
almost  always  causes  a  rise  of  pressure  and  perhaps  a  changed 
heart  rate.  Results,  as  a  rule,  upon  any  individual  show  lower 
values  after  the  novelty  of  the  procedure  has  worn  off,  and  the 
patient  submits  to  the  process  as  an  uninteresting  routine.  Under 
normal  conditions,  Potain*  estimated  the  systolic  pressure  in  the 
radial  of  the  adult  at  about  170  mms.  of  mercury  and  the  varia- 
tions for  different  ages  he  expressed  in  the  following  figures: 

Age 6-10        15        20        25        30        40        50        60        80 

Pressure  (systolic).    89      135      150      170      180      190      200      210      220 

Without  the  other  side  of  the  picture — that  is,  the  diastolic  pres- 
sure and  the  force  of  the  heart  beat  (pulse  pressure) — it  is  difficult 
to  interpret  these  figures.  The  rapid  increase  up  to  maturity 
probably  represents  chiefly  the  larger  output  of  blood  from  the  heart; 
the  slower  and  more  regular  increase  from  maturity  to  old  age  is 
due  possibly  to  the  gradual  hardening  of  the  arteries,  since  the  less 
*  "La  pression  arterielle  del'homme/'  Paris,  1902. 


VELOCITY   AND    PRESSURE    OF    BLOOD-FLOW.  509 

elastic  the  arteries  become,  the  greater  will  be  the  systolic  rise  with 
each  heart  beat.  Owing  to  the  method  Potain  used  these  figures 
are  all  undoubtedly  too  high,  but  the  relative  values  are  probably 
correct.  With  his  more  complete  apparatus  Erlanger  reports 
that  in  the  adult  (20  to  25),  when  the  psychical  factor  is  ex- 
cluded, the  average  pressure  in  the  brachial  is  110  mms.,  systolic, 
and  65  mms.,  diastolic, — figures  much  lower  than  those  given  by 
Potain.  Von  Recklinghausen's  figures  for  the  same  artery  are, 
systolic  pressure  116  mms.  Hg,  diastolic  pressure  73  mms.  Hg. 

Erlanger  and  Hooker  report  observations  upon  the  effect 
of  meals,  of  baths,  of  posture,  the  diurnal  rhythm,  etc.* 

The  effect  of  meals  is  particularly  instructive  in  that  it  illustrates 
admirably  the  play  of  the  compensatory  mechanisms  of  the  circu- 
lation by  means  of  which  the  heart  and  the  blood-vessels  are  ad- 
justed to  each  other's  activity.  During  a  meal  there  is  a  dilatation 
of  the  blood-vessels  in  the  abdominal  area,  or,  as  it  is  frequently 
called  in  physiology,  the  splanchnic  area,  since  it  receives  its 
vasomotor  fibers  through  the  splanchnic  nerve.  The  natural 
effect  of  this  dilatation,  if  the  other  factors  of  the  circulation 
remained  constant,  would  be  a  fall  of  pressure  in  the  aorta  and  a 
diminution  in  blood-flow  to  other  organs,  such  as  the  skin  and  the 
brain.  This  tendency  seems  to  be  compensated,  however,  by  an 
increased  output  of  blood  from  the  heart.  Observations  with  the 
sphygmomanometer  show  that  after  full  meals  there  is  a  marked 
increase  in  the  pulse  pressure,  indicating  a  more  effective  beat  of  the 
heart.  So  far  as  the  effect  on  the  heart  is  concerned,  the  result  of  a 
meal  is  similar  to  that  of  muscular  exercise,  and  this  reaction  may 
account  for  the  fact,  not  infrequently  observed,  that  in  elderly 
people  whose  arteries  are  rigid  an  apoplectic  stroke  may  follow  a 
heavy  meal. 

The  Method  of  Determining  Venous  Pressures  and  Capillary 
Pressures  in  Man. — A  number  of  methods  have  been  proposed 
for  determining  venous  pressures  in  man,  the  simplest  being 
that  described  by  Gaertner.f  It  consists  simply  in  raising 
slowly  the  arm  of  the  patient  until  the  veins  on  the  back  of  the 
hand  just  disappear.  The  height  above  the  heart  at  which  this 
occurs  gives  the  venous  pressure  in  the  right  auricle,  since  the 
vein  may  be  considered  as  a  manometer  tube  ending  in  the 
auricle.  In  this  and  in  other  methods  of  measuring  venous 
pressures,  and  the  same  is  true,  of  course,  of  arterial  and  capillary 
pressures,  there  must  be  some  agreement  as  to  what  constitutes 
the  heart-level,  since  the  highest  and  lowest  points  of  the  heart 
when  the  individual  is  standing  or  sitting  may  differ  by  as  much 

*  Erlanger  and  Hooker,  "The  Johns  Hopkins  Hospital  Report,"  vol.  xii, 
1904. 

t  Muench.  mediz.  Wochenschrift,"  1903,  1904. 


510  CIRCULATION    OF    BLOOD    AND    LYMPH. 

as  15  centimeters,  von  Recklinghausen  proposes  the  level 
made  by  a  dorsoventral  line  drawn  from  the  bottom  of  the 
sternum  (costal  angle)  to  the  spinal  column.  This  author*  has 
devised  a  simple  apparatus  for  determining  venous  and  capillary 
pressures,  the  principle  of  which  is  shown  by  the  schema  repre- 
sented in  Fig.  206. 

A  circular  bag  of  thin  rubber  with  a  diameter  of  about  5j  cm.  is  provided 
with  a  central  opening  of  2  cm.  The  bag  is  connected  with  a  pump  so  that 
it  can  be  blown  up,  and  the  degree  of  pressure  exerted  is  measured  by  an 
attached  manometer.  This  bag,  moistened  with  glycerine,  is  laid  upon  a 
vein,  as  represented  in  the  diagram.  It  is  covered  by  a  glass  plate  held  firmly 
in  position  and  the  bag  is  then  blown  up  until  the  vein  disappears;  the  pressure 
at  which  this  happens  is  shown  by  the  manometer  and  marks  the  pressure 


Fig.  206. — To  illustrate  the  method  of  measuring  venous  pressure:  H,  The  back  of 
the  hand  in  which  a  single  vein  is  represented;  B,  the  circular  rubber  bag  with  central 
opening,  and  with  a  tube,  T,  which  leads  to  the  pump  and  the  manometer;  G,  glass  plate 
held  over  the  rubber  bag.  The  bag,  B,  is  blown  up  by  pressure  through  the  tube  T  until 
the  vein  is  collapsed.  The  pressure  at  which  this  occurs,  or  the  pressure  at  which  the 
vein  reappears  as  the  bag  is  allowed  to  empty,  gives  the  pressure  within  the  vein. —  (von 
Recklinghausen.) 

within  the  vein.  A  convenient  modification  of  this  apparatus,  which  has 
been  described  by  Hooker,  +  is  shown  in  Fig.  207.  A  small  glass  chamber  is 
fastened  on  the  hand  over  a  vein  by  means  of  a  film  of  collodion  solution. 
The  interior  of  the  chamber  is  connected  by  rubber  tubing  with  a  water 
manometer  and  a  pressure  bulb.  By  means  of  the  latter  the  air  pressure  on 
the  vein  may  be  raised  until  the  vein  is  just  obliterated  and  the  pressure  used 
is  indicated  on  the  manometer  in  centimeters  of  water. 

With  instruments  of  this  kind  the  degree  of  pressure  neces- 
sary to  obliterate  a  given  vein  in  the  arm,  hand,  or  foot  can 
be  determined  readily  in  terms  of  a  column  of  water,  but  it 
is  obvious  that  for  any  given  vein  this  pressure  will  vary  with 
the  position  of  the  vein.  When  the  hand  hangs  pendent  at 
the  side  the  pressure  within  its  veins  will  be  greater  than  when 
the  hand  is  raised  to  the  heart-level.  The  pressure  actually 
measured  for  any  given  position  of  the  hand  or  foot  must, 
therefore,  be  corrected  for  the  heart-level  by  determining  the 
vertical  distance  between  the  vein  and  the  heart  (costal  angle), 
and  subtracting  this  distance,  expressed  in  centimeters,  from 

*  Von  Recklinghausen,  "Archiv  f.  exper.  Pathol.  u.  Pharmakol.,"  55,  470, 
1906. 

t  Hooker,  "American  Journal  of  Physiology,"  35,  73,  1914;  also  Eyster  and 
Hooker,  "Johns  Hopkins  Hospital  Bulletin,"  274,  1908. 


VELOCITY    AND    PRESSURE    OF    BLOOD-FLOW. 


511 


the  pressure,  also  expressed  in  centimeters,  which  was  found, 
necessary  to  obliterate  the  vein.  Measurements  made  by  this 
method  and  corrected  for  the  heart-level  show  that  in  the  normal 
person  the  pressure  within  the  small  veins  of  the  hand  or  arm 
varies  in  general,  for  the  adult,  between  10  and  20  cm.  of  water. 
The  average  pressure  seems  to  increase  progressively  during  life, 
from  a  value  of  8  cm.  in  early  youth  to  25  cm.  in  old  age.*  Un- 


rig. 207. — Hooker's  venous  pressure  apparatus.  A  glass  capsule,  A,  is  fastened  to  the  skin 
over  a  vein  by  means  of  a  solution  of  collodion.  This  capsule  is  connected  by  rubber  tubing 
with  a  pressur^bulb,  C,  and  a  water  manometer,  M .  By  means  of  the  bulb  the  pressure  is 
raised  in  A  until  the  vein  is  obliterated.  The  pressure  at  which  this  occurs  is  shown  by  the 
level  of  the  liquid  in  the  manometer.  This  pressure,  expressed  in  centimeters  of  water,  is  cor- 
rected by  subtracting  the  distance  between  the  vein  and  the  costal  angle,  as  indicated  on  the 
metal  rod  supporting  the  hand.  B  gives  an  enlarged  view  of  the  glass  capsule. 

usual  or  pathological  conditions  which  cause  a  congestion  in  the 
venous  side  of  the  heart  will  raise  the  venous  pressure  correspond- 
ingly, f 

When  the  venous  pressure  is  measured  in  the  small  veins  of  the  feet  in  a 
person  while  standing  we  should  suppose  that  after  a  reduction  to  the  heart 
level  it  would  be  about  the  same  as  that  noted  for  the  veins  of  the  hands, 
since  the  vessels  are  of  about  the  same  order  with  reference  to  their  distance 


loc. 


512  CIRCULATION    OF    BLOOD    AND    LYMPH. 

from  the  capillary  bed.  In  a  series  of  observations  of  this  kind,  reported  by 
von  Recklinghausen,  it  was  found,  on  the  contrary,  that  after  subtracting  the 
distance  between  the  foot  and  the  heart,  the  pressure  within  the  veins  was 
negative  by  as  much  as  40  cm.  The  author  explains  this  unexpected  result 
by  supposing  that  the  flow  through  the  foot  got  up  only  enough  pressure  in 
the  veins  to  lift  the  blood  to  the  level  of  the  pelvis,  and  that  the  complete 
closure  of  the  venous  valves  at  this  level  protected  the  veins  from  the  full 
pressure  of  the  column  of  blood.  Eventually,  no  doubt,  the  pressure  in  the  veins 
would  have  risen  sufficiently  to  lift  the  blood  to  the  heart-level,  but  it  seems 
probable  that  under  the  ordinary  conditions  of  life  this  result  is  effected  by 
the  cooperation  of  the  muscles  of  the  legs  and  the  respiratory  movements  of  the 
thorax  (see  p..  520) .  The  contractions  of  these  muscles,  aided  by  the  venous 
valves,  squeeze  the  blood  upward  to  the  heart.  The  fact  that  in  standing 
quietly  the  flow  through  the  feet  may  be  suspended  or  impeded,  for  a  time 
at  least,  throws  some  light,  as  von  Recklinghausen  suggests,  upon  the  fact 
that  it  is  so  difficult  to  stand  for  any  length  of  time  without  moving. 

The  apparatus  described  above  may  be  used  for  determining 
capillary  as  well  as  venous  pressures,  according  to  the  principle 
described  on  p.  501.  For  this  purpose  the  pressure  box  is  laid 
upon  a  given  skin  area  and  the  pressure  is  raised  until  the  skin 
beneath  is  blanched.  The  pressure  is  then  lowered  slowly  until 
the  skin  again  reddens,  showing  the  reestablishment  of  the  capil- 
lary flow.  The  pressure  thus  obtained  is  corrected  as  described 
for  the  level  of  the  heart.* 

*  For  some  technical  details,  see  von  Recklinghausen,  loc.  cit. 


CHAPTER  XXVI. 

THE  PHYSICAL  FACTORS  CONCERNED  IN  THE  PRO- 
DUCTION  OF  BLOOD-PRESSURE  AND  BLOOD- 
VELOCITY. 

$ 

In  the  preceding  pages  some  of  the  essential  facts  have  been 
stated  regarding  the  pressure  and  the  velocity  of  the  blood  in  the 
different  parts  of  the  vascular  system.  We  may  now  consider  the 
physical  factors  that  are  concerned  in  the  production  and  main- 
tenance of  these  peculiarities.  The  problem  as  it  actually  exists  in 
the  circulation,  with  its  elastic  vessels  varying  in  size  from  the 
aorta,  with  an  internal  diameter  of  nearly  20  mms.,  to  the  capil- 
laries, with  a  diameter  of  0.009  mm.,  is  extremely  complex,  but  the 
general  static  and  dynamic  principles  involved  are  simple  and  easily 
understood. 

Side  Pressure  and  Velocity  Pressure. — When  water  flows 
through  a  tube  under,  let  us  say,  a  constant  head  of  pressure  it 
encounters  a  resistance  due  to  the  friction  between  the  walls  of  the 
vessel  and  the  particles  of  water.  This  resistance  will  be  greater, 
the  narrower  the  tube.  A  part  of  the  head  of  pressure  used  to  drive 
the  liquid  along  the  tube  will  be  used  in  overcoming  this  resistance 
to  its  movement,  and  the  volume  of  the  outflow  will  be  correspond- 
ingly diminished.  If  we  use  an  apparatus  such  as  is  represented  in 
Fig.  208,  consisting  of  a  reservoir,  H,  and  a  long  outflow  tube, 
1,  2,  3,  4,  5,  the  outflow  from  the  end  and  the  pressure  along  the 
tube  may  be  measured  directly.  We  must  suppose  that  the  head 
of  pressure — that  is,  the  height  of  the  water  in  H — is  kept  constant 
by  some  means.  The  resistance  or  tension  due  to  the  friction  in  the 
tube  may  be  measured  at  any  point  by  inserting  a  side-tube  or 
gauge  (piezometer)  at  that  point.  The  liquid  will  rise  in  this  tube 
to  a  level  corresponding  to  the  pressure  or  resistance  offered  to  the 
movement  of  the  liquid  at  that  point — that  is,  the  weight  of  the 
column  of  liquid  will  measure  the  pressure  at  that  point  upon  a 
surface  corresponding  to  the  cross-area  of  the  tube.  The  pressure 
or  tension  at  any  point  may  be  spoken  of  as  the  side  pressure  or 
lateral  pressure,  and  it  expresses  the  amount  of  resistance  offered 
to  the  flow  of  the  liquid  because  of  the  friction  exerted  upon  the 
water  by  the  walls  of  the  tube  between  that  point  and  the  exit. 
This  side  pressure  increases  in  a  straight  line  from  the  point  of  exit 
33  513 


514 


CIRCULATION    OF    BLOOD    AND    LYMPH. 


to  the  reservoir,  and  this  in  general  is  the  picture  presented  by 
the  circulation.  The  reservoir,  the  head  of  pressure,  is  represented 
by  the  aorta,  the  exit  for  the  outflow  by  the  opening  of  the  vense 
cavae  into  the  right  auricle,  and  the  side  pressure  or  internal  tension 
of  the  blood  due  to  friction  against  the  walls  of  the  vessels  increases 
from  the  vense  cavse  back  to  the  aorta.  If  from  aorta  to  vena  cava 
the  vessels  were  of  the  same  diameter  the  increase  would  be  in  a 
straight  line,  as  in  the  case  of  the  model.  In  this  model  it  will  be 
noticed  that  the  straight  line  showing  the  side  pressure  does  not 
strike  the  top  of  the  column  of  liquid  in  the  reservoir,  but  corre- 
sponds to  a  certain  height,  h'.  This  expresses  the  fact  that,  of  the 
total  head  of  pressure  in  the  reservoir,  which  we  may  designate  as 
H,  a  certain  portion  only,  but  a  large  portion,  h',  is  used  in  over- 


Fig.  208. — Schema  to  illustrate  the  side  pressure  due  to  resistance,  and  the  velocity  pres- 
sure (TigerstedO:  H,  A  reservoir  containing  water;  1,  2,  3,  4,  5,  the  outflow  tube  with 
gauges  set  at  right  angles  to  measure  the  side  pressure;  h',  the  portion  of  the  total  pressure 
used  in  overcoming  the  resistance  to  the  flow ;  h,  the  portion  of  the  total  pressure  used  in 
moving  the  column  of  liquid — the  velocity  pressure. 

coming  the  resistance  along  the  tube.  What  is  left — that  is,  H-h', 
represents  the  force  that  is  employed  in  driving  the  liquid  through 
the  tube  with  a  certain  velocity ;  this  portion  of  the  pressure  we  may 
speak  of  as  the  velocity  pressure,  h.  If  in  measuring  the  side  pressure 
at  any  point  the  gauge  were  prolonged  into  the  tube  and  bent  so  as 
to  face  the  stream,  this  velocity  pressure  would  add  itself  to  the 
side  pressure  at  that  point  and  the  water  would  rise  to  a  higher 
level  in  this  particular  tube.  There  are  two  important  differences 
between  the  circulation  as  it  exists  in  the  body  and  that  repre- 
sented by  the  model.  In  the  body,  in  the  first  place,  we  have 
the  area  of  capillaries,  small  arteries,  and  veins,  intercalated  be- 
tween the  large  arteries  on  one  side  and  the  veins  on  the  other; 
and,  in  the  second  place,  the  vessels,  especially  the  arteries,  are 
extensible  and  elastic.  The  effect  caused  by  the  first  of  these 


BLOOD-PRESSURE    AND    BLOOD-VELOCITY. 


515 


factors — namely,  a  great  resistance  placed  in  the  middle  of  the 
course — may  be  illustrated  by  the  model  shown  in  Fig.  209,  which 
differs  from  that  in  Fig.  208  in  having  a  stopcock  in  the  outflow 
tube,  which,  when  partly  turned  off,  makes  a  narrow  opening  and  a 
relatively  great  resistance.  When  the  stopcock  is  open  the  pressure 
falls  equally  throughout  the  tube,  provided  the  bore  of  the  stopcock 
is  equal  to  that  of  the  tube.  If,  however,  it  is  partially  turned  the 
side  pressure  is  much  increased  between  it  and  the  reservoir  on  what 
we  may  term  the  arterial  side  of  the  schema,  and  it  is  correspond- 
ingly diminished  between  the  stopcock  and  the  exit,  on  the  venous 
side  of  the  schema.  Substantially  this  condition  prevails  in  the  body. 
The  capillary  region,  including  the  smallest  arterioles  and  veins, 
offers  a  great  resistance  to  the  flow  of  blood,  and  this  resistance  is 
spoken  of  in  physiology  as  the  peripheral  resistance.  Its  effect  is  to 


Fig.  209. — Schema  like  the  preceding  except  that  a  stopcock  is  inserted  at  the  middle 
of  the  outflow  to  imitate  the  peripheral  resistance  of  the  capillary  area.  The  relations  of 
the  internal  pressure  on  the  arterial  and  venous  sides  of  this  special  resistance  is  shown  by 
the  height  of  the  water  in  the  gauges. 

raise  the  pressure  on  the  arterial  side  and  lower  it  on  the  venous  side. 
When  other  conditions  in  the  circulation  remain  constant  it  is  found 
that  an  increase  in  peripheral  resistance,  caused  usually  by  a  con- 
striction of  the  arterioles,  is  followed  by  a  rise  of  arterial  pressures 
and  a  fall  of  venous  pressures.  On  the  contrary,  a  dilatation  of  the 
arterioles  in  any  organ  is  followed  by  a  fall  of  pressure  in  its  artery  or 
arteries  and  a  rise  of  pressure  in  its  veins.  The  effect  of  the  elastic- 
ity of  the  arteries  is  of  importance  in  connection  with  the  fact  that 
in  reality  the  circulation  is  charged  with  blood  not  from  a  constant 
reservoir  as  in  the  models,  Figs.  208  and  209,  but  by  the  rhythmical 
beats  of  the  heart.  If  the  vascular  system  were  perfectly  rigid  each 
rhythmical  charge  into  the  aorta  would  be  followed  by  an  equal  dis- 
charge from  the  venae  cavse,  the  pressure  throughout  the  system 
would  rise  to  a  high  point  during  systole  and  fall  to  a  low  point  dur- 


516  CIRCULATION    OF    BLOOD    AND    LYMPH. 

ing  the  diastole.  The  elasticity  of  the  arteries,  in  connection  with 
the  peripheral  resistance,  makes  an  important  difference.  As  the 
heart  discharges  into  the  aorta  the  pressure  rises,  but  the  walls  of 
the  arterial  system  are  distended  by  the  increased  pressure,  and 
during  the  following  diastole  the  recoil  of  these  distended  walls 
maintains  a  flow  of  blood  through  the  capillaries  into  the  veins. 
With  a  certain  rapidity  of  heart  beat  the  distention  of  the  arterial 
walls  is  increased  to  such  a  point  that  the  outflow  through  the  capil- 
laries into  the  veins  is  as  great  during  diastole  as  during  svstole ;  the 
rhythmical  flow  in  the  arteries  becomes  converted  by  the  elastic 
tension  of  the  overfilled  arterial  system  into  a  continuous  flow  in 
the  capillaries  and  veins.  This  effect  may  be  illustrated  by  a  simple 
schema  such  as  is  represented  in  Fig.  210.  A  syringe  bulb  (a),  rep- 
resenting the  heart,  is  connected  by  a  short  piece  of  rubber  tubing  to  a 
glass  tube  (6),  and  also  by  a  piece  of  distensible  band  tubing  (e)  with 


Fig.  210. — Simple  schema  to  illustrate  the  factors  producing  a  constant  head  of  pres- 
sure in  the  arterial  system :  o,  A  syringe  bulb  with  valves,  representing  the  heart ;  6,  glasa 
tube  with  fine  point  representing  a  path  with  resistance  alone,  but  no  extensibility  (the  out- 
flow is  in  spurts  synchronous  with  the  strokes  of  the  pump) ;  c,  outflow  with  resistance  and 
also  extensible  and  elastic  walls  represented  by  the  large  rubber  bag,  e ;  the  outflow  is  a 
steady  stream  due  to  the  elastic  recoil  of  the  distended!  bag,  e. 

a  similar  glass  tube  drawn  to  a  fine  point  (c).  In  the  latter  case  the 
distensible,  elastic  tubing  represents  the  arterial  system,  and  the 
fine  pointed  glass  tube  the  peripheral  resistance  of  the  capillary  area. 
If  the  syringe  bulb  is  put  into  rhythmical  play  and  the  flow  is  directed 
through  tube  b  the  discharges  are  in  rhythmical  spurts,  but  if 
directed  through  tube  c  the  discharge  is  a  continuous  stream, 
since  the  force  of  the  separate  beats  becomes  stored  as  elastic  tension 
in  the  walls  of  the  band  tubing,  and  it  is  this  constant  force  which 
drives  a  steady  stream  through  the  capillary  point.  In  a  general 
way,  this  schema  gives  us  a  true  picture  of  the  conditions  in  the  cir- 
culation. The  rhythmical  force  of  the  heart  beat  is  stored  as  elastic 
tension  in  the  walls  of  the  arteries,  and  it  is  the  squeeze  of  these 
distended  walls  which  gives  the  continuous  driving  force  that  is 
responsible  for  the  constant  flow  in  the  capillaries  and  veins. 

Enumeration  of  the  Factors  Concerned  in  Producing  Nor- 
mal Pressure  and  Velocity. — In  the  normal  circulation  we  may 


BLOOD-PRESSURE    AND    BLOOD-VELOCITY.  517 

say  that  four  chief  factors  co-operate  in  producing  the  conditions 
of  pressure  and  velocity  as  we  find  them.  These  factors  are:  (1) 
The  heart  beat.  (2)  The  resistance  to  the  flow  of  blood  through  the 
vessels,  and  especially  the  peripheral  resistance  in  the  region  of  the 
small  arteries,  capillaries,  and  small  veins.  (3)  The  elasticity  of 
the  arteries.  (4)  The  quantity  of  blood  in  the  system.  The 
way  in  which  these  factors  act  may  be  pictured  as  follows :  Suppose 
the  system  at  rest  with  the  definite  quantity  of  blood  distributed 
equally  throughout  the  vascular  system.  The  internal  or  side 
pressure  throughout  the  system  will  be  everywhere  the  same, — 
probably  zero  (atmospheric)  pressure,  since  the  capacity  of  the 
vascular  system  is  sufficient  to  hold  the  entire  quantity  of  blood 
without  distension  of  its  walls.  If,  now,  the  heart  begins  to  beat 
with  a  definite  rhythm  and  discharges  a  definite  quantity  of  blood  at 
each  beat  the  whole  mass  will  be  set  into  motion.  The  arteries 
receive  the  blood  more  rapidly  than  it  can  escape  through  the  capil- 
laries into  the  veins,  and  consequently  it  accumulates  upon  the 
arterial  side  until  an  equilibrium  is  reached, — that  is,  a  point  at 
which  the  elastic  recoil  of  the  whole  arterial  tree  suffices  to  force 
through  the  capillaries  in  a  unit  of  time  as  much  blood  as  is  received 
from  the  heart  during  the  same  time.  In  this  condition  of  equilib- 
rium the  flow  in  capillaries  and  veins  is  constant,  and  the  side 
pressure  in  the  veins  increases  from  the  right  auricle  back  to  the 
capillaries.  In  the  arteries  there  is  a  large  side  pressure  throughout, 
owing  to  the  resistance  between  them  and  the  veins  and  especially 
to  the  great  resistance  offered  by  the  narrow  capillaries.  This 
pressure  rises  and  falls  with  each  discharge  from  the  heart,  and  the 
pulse  waves,  both  as  regards  pressure  and  velocity,  are  most  marked 
in  the  aorta  and  diminish  farther  out  in  the  arterial  tree,  failing 
completely  in  the  last  small  arterioles,  since  if  taken  together  these 
arterioles  constitute  a  large  and  distensible  tube  of  much  greater 
capacity  than  the  aorta. 

General  Conditions  Influencing  Blood-pressure  and  Blood- 
velocity. — Alterations  in  any  of  the  four  chief  factors  mentioned 
above  must,  of  course,  cause  a  change  in  pressure  and  velocity. 

I.  An  increase  in  the  rate  or  force  of  the  heart  beat  will  increase 
the  velocity  of  the  flow  throughout  the  system,  although,  of  course, 
that  general  difference  in  velocity  in  the  arteries,  capillaries,  and 
veins  which  depends  upon  the  variations  in  width  of  bed  will  remain. 
Such  a  change  will  also  cause  a  rise  of  pressures  throughout  the 
system.  The  energy  exhibited  in  the  vascular  system  as  side  pres- 
sure, velocity  pressure,  etc.,  comes,  in  the  long  run,  mainly  from 
the  force  of  contraction  of  the  heart  muscle.  This  force  is  what  is 
represented  in  the  model,  Fig.  208,  as  the  total  head  of  pressure  ( H). 
An  increase  in  rate  or  force  of  heart-beat  is  equivalent,  therefore, 


518  CIRCULATION    OF    BLOOD    AND    LYMPH. 

to  an  increase  in  this  head  of  pressure,  and  along  with  the  increase 
in  velocity  thus  caused  there  is  an  increased  friction  or  resistance. 

II.  An  increase  or  decrease  in  the  width  of  the  vessels  will 
influence  both  the  resistance  to  the  flow  and  the  velocity.     Under 
normal  conditions  it  is  the  small  arteries  that  are  constricted  or 
dilated  (vasoconstriction  and  vasodilatation) .     A  constriction  of 
these  arteries  causes  an  increase  in  arterial  pressures  and  a  decrease 
in  venous  pressure.    The  velocity  of  the  blood-flow  is  decreased. 
A  dilatation  has  the  opposite  effects.     Numerous  instances  of  this 
relation  will  be  referred  to  in  describing  the  physiology  of  the  vaso- 
motor  nerves. 

III.  A  diminution  in  elasticity  of  the  arteries   will  tend  to 
interfere  with  the  constancy  of  the  flow  from  the  arteries  into  the 
capillaries,  and  in  the  arteries  themselves  the  swings  of  pressure 
from  systolic   to   diastolic   during   the   heart   beat  will   be  more 
extensive.     This  latter  fact  can  be  shown  upon  elderly  individuals 
whose  arteries  are  becoming  rigid,  but  whether  a  change  of  this 
character  is  ever  so  advanced  in  human  beings  as  to  seriously  modify 
the  capillary  circulation  does  not  appear  to  have  been  investigated. 

IV.  A  loss  of  blood,   other  conditions  remaining  the  same, 
will  also  cause  a  fall  in  blood-pressures  and  velocity.    As  a  matter 
of  fact,  however,  a  considerable  amount  of  blood  may  be  lost  with- 
out any  marked  permanent  change  in  arterial  blood-pressure.     The 
reason  for  this  result  is  found  in  the  adjustability  or  adaptability 
of  the  vascular  system.     It  is  in  such  respects  that  the  system  differs 
greatly  from  a  rigid  schema  such  as  we  use  for  our  models.     When 
blood  is  withdrawn  from  the  vessels  the  loss  may  be  offset  by  an 
increased  action  of  the  heart  and  by  a  contraction  of  the  arterioles, 
the  two  effects  combining  to  give  a  normal  or  approximately  normal 
arterial  pressure.    To  carry  out  the  analogy  with  the  model  (Fig. 
208)  if  by  chance  some  of  the  store  of  water  was  lost  we  might  sub- 
stitute a  narrower  reservoir,  so  that  with  a  diminished  supply  we 
could  still  maintain  the  same  level  of  pressure.     In  the  body, 
moreover,  a  loss  of  blood  by  hemorrhage  may  be  compensated  in 
part,  so  far  as  the  bulk  of  the  liquid  is  concerned,  by  a  flow  of 
liquid  from  the  tissues  into  the  blood-vessels. 

The  Hydrostatic  Effect. — In  the  living  animal,  especially  in 
those,  like  ourselves,  that  walk  upright,  the  actual  pressure  in  the 
arteries  of  the  various  tissues  must  vary  much  also  with  the  position. 
For  instance,  in  standing  erect  the  small  arteries  in  the  hands  or 
feet  are,  in  addition  to  other  conditions  noted  above,  exposed  to  the 
weight  of  the  column  of  arterial  blood  standing  over  them.  In 
the  pendent  arm  the  skin  of  the  fingers  is  congested;  if,  however, 
the  arm  is  raised  above  the  head  the  skin  may  become  blanched 
because  now  the  column  of  blood  from  fingers  to  shoulder  exercises 


BLOOD-PRESSURE    AND    BLOOD-VELOCITY.  519 

a  hydrostatic  pressure  in  the  opposite  direction.  In  determinations 
of  blood-pressure  in  the  brachial  artery  of  man  care  should  be  taken 
to  keep  the  arm  in  the  same  position  in  a  series  of  observations  in 
order  to  equalize  the  effect  of  the  hydrostatic  factor.  The  impor- 
tance of  this  gravity  effect  is  most  evident  in  the  case  of  the  ab- 
dominal (splanchnic)  circulation.  When  an  animal  accustomed 
to  go  on  all  fours  is  held  in  a  vertical  position  the  great  vascular 
area  of  the  abdomen  is  placed  under  an  increased  pressure  due  to 
gravity,  and,  unless  there  is  a  compensatory  contraction  of  the 
arterioles  or  of  the  abdominal  .wall,  so  much  blood  may  accumulate 
in  this  portion  of  the  system  that  the  arterial  pressure  in  the  aorta 
will  fall  markedly  or  the  circulation  may  stop  entirely.*  In  most 
cases  the  compensation  takes  place  and  no  serious  change  in  the 
circulation  results.  In  rabbits,  however,  which  have  lax  abdominal 
walls,  it  is  said  that  the  animal  may  be  killed  by  simply  holding  it 
in  the  erect  position  for  some  time.  For  the  same  reason  an  erect 
posture  in  man  may  be  dangerous  when  the  compensatory  nervous 
reflexes  controlling  the  arteries  and  the  tone  of  the  abdominal  wall 
are  thrown  out  of  action,  as,  for  instance,  in  a  faint  or  in  a  condition 
of  anesthesia.  In  such  conditions  the  recumbent  position  favors 
the  maintenance  of  the  normal  circulation.  Indeed,  under  ordinary 
conditions  some  individuals  are  quite  sensitive  to  the  effects  of  a 
vertical  position,  especially  if  unaccompanied  by  muscular  or  mental 
activity,  and  may  suffer  from  giddiness  and  a  sense  of  faintness 
in  consequence  of  a  fall  in  general  blood-pressure.  It  seems  prob- 
able that  in  these  cases  the  gravity  effect  has  drafted  off  an  undue 
amount  of  blood  into  the  splanchnic  area.  Individuals  who  have 
been  kept  in  bed  for  long  periods  by  sickness,  accident,  or  other 
causes  suffer  from  giddiness  and  unsteadiness  when  they  first 
attempt  to  stand  or  walk.  It  seems  quite  possible  that  in  such 
cases  the  effect  is  caused  by  a  fall  in  arterial  pressure  brought 
about  by  the  dilatation  in  the  splanchnic  area.  The  added 
weight  of  blood  thrown  on  these  vessels  by  the  effect  of  gravity 
is  not  compensated  by  a  vasoconstriction  of  the  arterioles  or  an 
increased  tone  in  the  abdominal  walls.  While  certain  general 
deductions  of  the  kind  given  above  may  be  made  from  our 
knowledge  of  the  hydrodynamics  and  hydrostatics  of  the  cir- 
culation, it  is  evident  that  in  particular  cases,  whether  affecting 
special  organs  or  the  organism  as  a  whole,  it  is  necessary  to 
obtain  directly,  if  possible,  the  facts,  not  only  for  the  arterial 
pressure  and  velocity  but  also  for  the  venous  pressure  and 
velocity,  in  order  to  draw  safe  conclusions  as  to  the  changes  in 
the  circulation.  In  all  observations  made  upon  man  it  is 
especially  important  to  standardize  the  results  by  reducing 
*  Hill  and  Barnard,  " Journal  of  Physiology,"  21,  321,  1897. 


520  CIRCULATION    OF   BLOOD    AND    LYMPH. 

them  to  a  common  level,  that  is,  to  the  level  of  the  heart  at  the 
costal  angle  (p.  510). 

Accessory  Factors  Aiding  the  Circulation. — The  force  of  the 
heart  beat  is  the  main  factor  concerned  in  the  movement  of  the 
blood,  but  certain  other  muscular  movements  aid  more  or  less  in 
maintaining  the  circulation  as  it  actually  exists  in  the  living  animal, 
particularly  in  their  effect  upon  the  flow  of  blood  in  the  veins. 
The  most  important  of  these  accessory  factors  are  the  respiratory 
movements  and  the  contractions  of  the  muscles  of  the  limbs  and 
viscera.  At  each  inspiratory  movement  the  pressure  relations  are 
altered  in  the  thorax  and  abdomen,  and  reverse  changes  occur  dur- 
ing expiration.  These  effects  influence  the  flow  of  blood  to  the 
heart,  and  alter  the  velocity  and  pressure  of  the  blood  in  a  way  that 
is  described  in  the  section  on  Respiration  under  the  title  of  The 
Respiratory  Waves  of  Blood-pressure.  In  brief,  it  may  be  said 
that  the  main  effect  of  the  respiratory  movements  is  to  force  or  to 
suck  blood  from  the  large  veins  of  the  abdomen  and  neck  into  the 
large  thoracic  veins,  and,  therefore,  into  the  right  side  of  the  heart. 
Keith*  has  called  attention  to  the  fact  that  the  system  of  large 
veins  in  the  thorax  and  abdomen,  namely,  the  superior  and  in- 
ferior venae  cavse,  the  innominate,  iliac,  hepatic,  and  renal  veins 
constitute  what  he  calls  a  venous  cistern,  whose  capacity  may  be 
reckoned  as  about  400  to  500  c.c.  This  cistern  is  shut  off  below 
from  the  veins  of  the  lower  extremity  by  the  valves  in  the  femoral 
veins  at  their  entrance  into  the  pelvis;  it  is  shut  off  from  the  veins 
of  the  upper  extremity  by  valves  in  the  subclavian  veins,  and  from 
the  veins  of  the  neck  and  head  by  the  jugular  valves.  When  an 
inspiration  is  made,  the  lowered  pressure  in  the  thoracic  cavity 
aspirates  blood  from  the  veins  in  the  neck  and  upper  extremities 
into  the  superior  cava,  and  on  the  return  to  the  expiratory  position 
blood  cannot  be  forced  back  owing  to  the  jugular  and  subclavian 
valves.  In  the  same  way  the  lessened  intrathoracic  pressure  during 
inspiration  must  tend  to  aspirate  blood  from  the  abdominal  portion 
of  the  inferior  vena  cava  into  the  thoracic  portion,  and  this  move- 
ment of  blood  into  the  thorax  is  probably  aided  by  the  rise  in 
pressure  in  the  abdomen  caused  by  the  descent  of  the  diaphragm, 
since  an  increase  of  pressure  in  the  abdomen  would  be  prevented 
from  driving  blood  toward  the  legs  by  the  presence  of  the  femoral 
valves.  The  play  of  the  respiratory  movements  must,  therefore, 
constitute  a  constant  factor  tending  to  empty  the  venous  cistern 
into  the  right  heart,  and  in  this  way  promoting  the  circulation  on 
the  venous  side.  Contractions  of  the  skeletal  muscles  must  also 
influence  the  blood-flow.  The  thickening  of  the  fibers  in  con- 
traction squeezes  upon  the  capillaries  and  small  vessels  and  tends 
*  Keith,  "Journal  of  Anatomy  and  Physiology,"  42,  1,  1908. 


BLOOD-PRESSURE    AND    BLOOD-VELOCITY.  521 

to  empty  them.  On  account  of  the  valves  in  the  veins  the  blood 
is  forced  mainly  toward  the  venous  side  of  the  heart,  so  that 
rhythmical  contractions  of  the  muscles  may  accelerate  the  cir- 
culation. This  pumping  effect  of  our  muscular  movements  is 
probably  quite  an  important  factor  in  returning  the  blood  from 
the  lower  extremities.  In  this  portion  of  the  body  the  venous 
flow  to  the  heart  has  to  overcome  the  hydrostatic  pressure  of  the 
column  of  blood,  and  it  has  been  shown  that  when  one  is  standing 
quite  still,  the  venous  pressure  alone  may  be  insufficient  to  overcome 
this  resistance,  so  that  the  blood-flow  from  the  feet  may  be  much 
retarded.  Under  these  circumstances  movements  of  the  legs,  as 
in  walking,  aided  by  the  valves  in  the  veins,  probably  help  to 
"  milk  "  the  blood  into  the  pelvic  veins.  The  contractions  of  the 
smooth  muscles,  especially  in  the  stomach  and  intestines,  during 
digestion  have  a  similar  effect.  The  musculature  of  the  spleen 
also  is  supposed  to  aid  the  circulation  through  that  organ  by  its 
rhythmical  contractions. 

The  Conditions  of  Pressure  and  Velocity  in  the  Pulmonary 
Circulation. — The  general  plan  of  the  smaller  circulation  from 
right  ventricle  to  left  auricle  is  the  same  as  in  the  major  or  systemic 
circulation,  and  the  same  general  principles  hold.  The  right 
ventricle  pumps  its  blood  into  the  pulmonary  artery,  and,  on  ac- 
count of  the  peripheral  resistance  in  the  lung  capillaries,  the  side 
pressure  in  the  artery  is  higher  than  in  the  capillaries,  and  higher  in 
these  than  in  the  pulmonary  veins.  The  velocity  of  movement  is 
least,  on  the  other  hand,  in  the  extensive  capillary  area  and  greatest 
in  the  pulmonary  artery  and  veins,  on  account  of  the  variations  in 
width  of  the  bed.  So  also  in  the  pulmonary  artery  the  pressure  and 
velocity  must  fluctuate  between  a  systolic  and  diastolic  level  at  each 
heart  beat,  while  in  the  pulmonary  veins  they  are  more  or  less  uni- 
form. An  interesting  difference  between  the  two  circulations 
consists  in  the  fact  that  the  peripheral  resistance  is  evidently  much 
less  in  the  pulmonary  circuit,  and  consequently  the  pressure  in  the 
pulmonary  arteries  is  much  less  than  in  the  aortic  system.  The 
velocity  of  the  flow,  as  already  stated  (p.  491),  is  also  greater  in 
the  lung  capillaries  than  in  the  systemic  capillaries.  Exact  deter- 
minations of  the  pressure  in  the  pulmonary  artery  are  made  with 
difficulty  on  account  of  the  position  of  the  vessel.*  The  results 
obtained  by  various  observers  give  such  values  as  the  following: 

MEAN  PRESSURE.         EXTREME  VARIATIONS. 
MMS.  HG.  MMS.  Ho. 

Dog.. 20  10     to  33 

Cat 18  7.5  "  24.7 

Rabbit 12  6      "35 

*  For  a  discussion  of  the  special  physiology  of  the  pulmonary  circulatior 
and  for  references  to  literature,  see  Tigerstedt,  "Ergebnisse  der  Physiologic/ 
vol.  ii.,  part  ii.,  p.  528,  1903. 


522  CIRCULATION    OF    BLOOD    AND    LYMPH. 

It  will  be  seen,  therefore,  that  the  mean  pressure  is  not  more 
than  one-seventh  to  one-eighth  of  that  prevailing  in  the  aorta. 
The  thinner  walls  and  smaller  muscular  power  of  the  right  ventricle 
as  compared  with  the  left  are  an  indication  of  the  fact  that  less  force 
is  necessary  to  keep  up  the  circulation  through  the  pulmonary 
circuit. 

The  Variations  in  Pressure  in  the  Pulmonary  Circuit. — • 
Experimental  results  indicate  that  the  pressures  in  the  pulmonary 
circuit  do  not  undergo  as  marked  changes  as  in  the  systemic  circu- 
lation; the  flow  is  characterized  by  a  greater  steadiness.  With  a 
systemic  pressure,  as  taken  in  the  carotid,  varying  from  144  to  222 
mms.,  that  in  the  pulmonary  artery  changes  correspondingly  only 
from  20  to  26  mms.,  and  extreme  variations  of  pressure  in  the 
pulmonary  artery  probably  do  not  exceed,  as  a  rule,  15  to  20  mms. 
The  regulations  of  the  pressure  and  flow  of  blood  in  the  small 
circulation  do  not  seem  to  be  so  direct  or  complex  as  in  the  aortic 
system.  The  part  taken  by  the  vasomotor  nerves  is  referred  to 
in  the  chapter  upon  the  innervation  of  the  blood-vessels,  and 
attention  may  be  called  here  only  to  the  mechanical  factors,  which, 
indeed,  for  this  circulation  are  probably  the  most  important.  The 
output -from  the  right  ventricle,  and  therefore  the  amount  of  flow 
and  the  pressure  in  the  pulmonary  artery,  depend  mainly  on  the 
amount  of  blood  received  through  the  venae  cavae  by  the  right  auricle. 
If  one  of  the  venae  cavae  is  closed  the  pulmonary  pressure  sinks; 
pressure  upon  the  abdomen,  on  the  other  hand,  by  squeezing  more 
blood  toward  the  right  heart  may  raise  the  pressure  in  the  pulmonary 
artery.  By  such  means,  therefore,  the  variations  in  blood-flow  in 
the  systemic  circulation  indirectly  influence  and  control  the  pressure 
relations  in  the  pulmonary  circuit.  But  the  changes  in  the  systemic 
circulation  may  affect  the  blood-flow  through  the  lungs  in  still 
another  way, — namely,  by  a  back  effect  through  the  left  auricle. 
When  for  any  reason  the  blood-pressure  in  the  aorta  is'  driven 
much  above  the  normal  level  the  left  ventricle  may  not  be  able  to 
empty  itself  sufficiently,  and  if  this  happens  the  pressure  in  the 
left  auricle  will  rise  and  the  flow  through  the  lungs  from  right 
ventricle  to  left  auricle  will  be  more  or  less  impeded.  On  the  whole, 
it  would  seem  that  the  pulmonary  circulation  is  subject  to  less 
changes  than  in  the  case  of  the  organs  supplied  by  the  aorta.  The 
mechanical  conditions,  especially  in  the  capillary  region,  are  such 
that  the  blood  is  sent  through  the  lungs  with  a  relatively  high 
velocity,  although  under  small  actual  pressure.  The  special  effects 
of  the  respiratory  movements  and  of  variations  in  intrathoracic 
pressure  upon  the  pulmonary  circulation  are  referred  to  in  con- 
nection with  respiration. 


CHAPTER  XXVII. 
THE  PULSE. 

General  Statement. — When  the  ventricular  systole  discharges 
a  new  quantity  of  blood  into  the  arteries  the  pressure  within  these 
vessels  is  increased  temporarily.  If  the  arteries,  capillaries,  and 
veins  were  perfectly  rigid  tubes  it  is  evident  that  this  pressure  would 
be  transmitted  practically  instantaneously  throughout  the  system, 
and  that  a  quantity  of  blood  would  be  displaced  from  the  vense 
cavae  into  the  auricles  equal  to  the  quantity  forced  into  the  aorta  by 
the  ventricle.  The  flow  of  blood  throughout  the  vascular  system 
would  take  place  in  a  series  of  spurts  or  pulses,  the  pressure  rising 
suddenly  during  systole  and  falling  rapidly  during  diastole.  Since 
the  blood  is  incompressible  and  the  walls  of  the  vessels  if  rigid 
would  be  inextensible,  the  rise  of  pressure,  the  pulse,  would  be 
simultaneous  in  all  parts  of  the  system.  The  fact,  however,  that 
the  walls  of  the  vessels  are  extensible  and  elastic  modifies  the  trans- 
mission of  the  pulse  wave  in  several  important  particulars:  It 
explains  why  it  is  that  the  pulse  dies  out  in  or  at  the  beginning  of 
the  capillaries  and  why  it  occurs  at  different  times  in  different 
arteries — that  is,  why  the  wave  of  pressure  takes  a  perceptible 
time  to  travel  over  the  arteries.  The  result  that  follows  from  the 
elasticity  of  the  arteries  may  be  pictured  as  follows:  Under  the 
normal  conditions  of  the  circulation  when  the  heart  contracts  and 
forces  a  new  quantity  of  blood  into  the  aorta  room  must  be  made 
for  this  blood  either  by  moving  the  whole  mass  of  the  blood  forward 
— that  is,  by  discharging  an  equal  amount  at  the  other  end  into  the 
auricle — or  by  the  enlargement  of  the  arteries.  This  latter  alter- 
native is  what  substantially  happens,  as  it  takes  less  pressure  to  dis- 
tend the  arteries  than  to  move  forward  the  entire  mass  of  blood 
under  the  conditions  that  exist  in  the  body.  So  soon,  therefore,  as 
the  semilunar  valves  open  and  the  new  column  of  blood  begins  to 
enter  the  aorta,  the  walls  of  that  vessel  begin  to  expand,  and  during 
the  time  that  the  blood  is  flowing  oufrof  the  heart — that  is,  in  round 
numbers,  about  0.3  sec. — the  extension  of  the  walls  passes  from 
point  to  point  along  the  arterial  system,  since  the  increased  pressure 
is  transmitted  rapidly  over  the  arterial  system,  and  at  every  point 
in  its  progress  it  causes  an  expansion  of  the  arterial  wall  as  well  as  an 
acceleration  in  the  onward  movement  of  the  blood.  At  the  end  of 
the  outflow  from  the  heart  all  the  arteries  are  beginning  to  enlarge, 

523 


524  CIRCULATION    OF    BLOOD    AND    LYMPH. 

the  maximum  extension  being  in  the  aorta,  and  room  is  thus  made 
for  the  new  quantity  of  blood.  The  new  blood  that  is  actually  dis- 
charged from  the  heart  lies  somewhere  in  the  aorta.  With  the 
cessation  of  the  heart  beat  and  the  closure  of  the  semilunar  valves, 
the  sharp  recoil  of  the  distended  aorta  drives  forward  the  col- 
umn of  blood,  and  as  the  aorta  sinks  back  to  its  normal  diastolic 
diameter  the  more  distal  portions  of  the  arterial  system  are  at  first 
distended  to  a  certain  point  and  then  return  to  their  diastolic  size 
as  the  excess  of  blood  streams  through  the  capillaries  into  the  veins. 
At  the  time  that  the  aorta  has  reached  its  diastolic  size  the  walls 
of  the  most  distant  arterioles  have  passed  their  maximum  extension 
and  are  beginning  to  collapse.  The  distension  caused  by  the  pulse, 
therefore,  spreads  through  the  arterial  system  in  the  form  of  a  wave. 
At  any  given  point  the  distension  of  the  walls  increases  to  a  maxi- 
mum and  then  declines,  and  when  this  change  in  size  is  recorded 
in  the  large  arteries,  by  methods  described  below,  it  is  found  that 
the  expansion  of  the  artery  is  much  more  sudden  than  the  subse- 
quent collapse.  This  difference  is  understood  when  we  remember 
that  the  heart  throws  its  load  of  blood  into  the  arteries  with  sud- 
denness and  force,  causing  a  sharp  rise  of  pressure,  while  the  collapse 
of  the  arteries  is  due  to  their  own  elasticity.  The  disappearance 
of  the  pulse  before  reaching  the  capillary  area  is  readily  compre- 
hended when  one  remembers  that  the  arterial  tree  constantly  in- 
creases in  size  as  one  passes  out  from  the  aortic  trunk.  Many  facts, 
such  as  those  of  pressure  and  velocity  already  described,  indicate 
that  the  increase  in  capacity  of  the  arterial  system  is  somewhat 
gradual  until  the  region  of  the  smallest  arterioles  and  capillaries  is 
reached  and  that  at  this  point  there  is  a  sudden  widening  out  or 
increase  in  capacity  of  the  whole  system,  although  the  individual 
vessels  diminish  in  diameter.  It  is  in  this  region  that  the  pulse, 
under  ordinary  conditions,  becomes  imperceptible.*  When  the 
arterioles  in  any  organ  are  dilated  the  pulse  may  spread  through 
the  capillary  regions  and  be  visible  in  the  veins.  A  venous  pulse 
produced  in  this  way  may  be  observed,  for  example,  in  the  veins 
of  the  hand  during  sleep  (Hooker). 

Velocity  of  the  Pulse  Wave. — From  the  above  considerations 
it  is  evident  that  in  a  system  such  as  is  presented  by  our  blood- 
vessels the  velocity  of  the  pulse  wave  must  vary  with  the  rigidity 
of  the  tubes.  If  perfectly  rigid  the  pressure  would  be  transmitted 
practically  instantaneously;  if  the  walls  were  very  extensible  the 
propagation  would  be  relatively  slow.  For  our  blood-vessels  as 
they  exist  at  any  given  moment  the  velocity  of  the  pulse  wave  may 
be  estimated  by  a  simple  method :  Two  arteries  may  be  selected  at 

*  For  a  discussion  of  the  pulse  and  for  literature  consult  von  Frey,  "Die 
Untersuchung  des  Pulses,"  Berlin,  1892;  Wiggers,  "Circulation  in  Health 
and  Disease,"  1915.  For  a  description  of  the  variations  in  disease  consult 
Mackenzie,  "The  Study  of  the  Pulse,  etc.,"  New  York,  1902. 


THE    PULSE. 


525 


different  distances  from  the  heart  and  the  pulse  wave  as  it  passes  by 
a  given  point  in  each  artery  may  be  recorded  by  some  convenient 
apparatus,  such  as  can  be  devised  in  any  laboratory.  If  the  waves 
are  recorded  on  a  rapidly  revolving  kymographion  whose  rate  of 
movement  can  be  determined,  then  the  difference  in  time  in  the 
arrival  of  the  pulse  wave  at  the  two  points  is  easily  ascertained. 
That  there  is  a  perceptible  difference  in  time  one  can  easily  demon- 
strate to  himself  by  feeling  simultaneously  the  pulse  of  the  radial 
and  the  carotid  arteries.  If  this  difference  in  time  is  determined 
for  two  arteries — for  instance,  the  femoral  and  the  tibialis  anterior 
— and  the  distance  between'the  two  points  is  recorded,  we  have 
evidently  the  necessary  data  for  obtaining  the  velocity  of  the 
pulse  wave  in  the  arteries  of  that  region.  A  record  of  this  kind 
is  shown  in  Fig.  211. 


Fig.  211. — To  illustrate  the  method  of  determining  the  velocity  of  the  pulse  Miave 
in  man.  Shows  record  of  the  pulse  at  two  points  on  the  leg  at  a  known  distance  apart. 
The  difference  in  tune  is  given  by  the  verticals  dropped  from  the  beginning  of  these  waves 
to  the  time  curve.  This  last  is  made  by  the  vibrations  of  a  tuning  fork  giving  50  vibra- 
tions per  second.  The  difference  in  this  case  was  equal  to  0.07  sec. 


The  results  obtained  by  various  authors  indicate  that  the  velocity 
varies  somewhere  between  6  and  9  meters  per  second  for  adults. 
The  figures  published  by  later  observers  show  also  that  the  velocity 
is  somewhat  greater  in  the  upper  extremities  (7.5  m.  for  carotid- 
radial  estimation)  than  in  the  descending  aorta  (6.5  m.  for  carotid- 
femoral  estimation).*  The  average  of  thirty  determinations  made 
in  the  author's  laboratory  upon  medical  students  shows  that  the 
velocity  in  the  leg  (femoral-anterior  tibial)  is  6.1  m.  when  the 
records  are  made  upon  the  same  leg,  and  7.4  m.  when  the  record 
for  the  femoral  is  taken  from  one  leg  and  that  for  the  anterior  tibial 

*Edgren,  " Skandinavisches  Archiv  f.  Physiol.,"  1,  96,  1889. 


526  CIRCULATION    OF    BLOOD    AND    LYMPH. 

from  the  other.  The  latter  condition  would  seem  to  be  more  nor- 
mal, since  the  blood-flow  and  normal  tension  of  the  walls  are 
probably  less  disturbed.  An  increase  in  rigidity  of  the  arteries 
causes  the  velocity  to  rise;  in  elderly  people,  therefore,  the  velocity 
is  distinctly  greater.  In  arterial  sclerosis  with  hypertrophy  of  the 
heart  the  velocity  may  increase  to  as  much  as  11  or  13  m.  Any 
marked  dilatation  of  the  arteries — such  as  occurs,  for  instance, 
in  aneurysms, — retards  the  pulse  wave  markedly;  so  that  the 
existence  of  an  aneurysm  may  be  detected  in  some  cases  by  this 
fact.  If  we  know  the  velocity  of  the  wave  and  the  time  that  it  takes 
to  pass  any  given  point  the  length  of  the  wave  is  given  by  the 
formula  1=  vt.  In  an  adult  the  duration  of  the  wave  (t)  at  the  radial 
may  be  taken  as  0.5  to  0.7  sec.;  so  that  if  the  velocity  of  the  wave 
were  uniform  throughout  the  arteries  the  length  of  the  wave  would 
be  from  3.25  to  4.5  m.  We  can  conclude,  therefore,  that  before 


Fig.  212.— The  Dudgeon  sphygmograph  in  position. 

the  wave  has  disappeared  at  the  root  of  the  aorta  it  has  reached  the 
most  distant  arteries. 

The  Form  of  the  Pulse  Wave — Sphygmography. — The  pulse 
wave  may  be  felt  upon  any  superficial  artery  in  consequence  of  the 
distension  of  the  vessel.  By  the  tactile  sense  alone  the  experienced 
physician  may  distinguish  some  of  the  characters  of  the  wave,  its 
frequency,  its  force,  etc.  The  details  of  the  form  of  the  wave, 
however,  were  made  evident  only  when  the  variations  in  size  of  the 
artery  were  recorded  graphically  by  placing  a  lever  upon  it.  Any 
instrument  suitable  for  this  purpose  is  designated  as  a  sphygmo- 
graph, and  very  numerous  forms  have  been  devised.  The  move- 
ment of  the  artery  is  very  small  and  to  obtain  a  distinct  record  it  is 
necessary  to  magnify  this  movement  greatly  by  a  properly  con- 
structed lever. 

The  form  of  lever  that  is  perhaps  most  frequently  employed  is  shown  in  the 
accompanying  figures.  The  instrument  is  strapped  upon  the  arm  so  that  the 


THE    PULSE. 


527 


button  of  the  metallic  spring  rests  over  the  radial  artery.  The  movements 
of  the  artery  are  transmitted  to  this  spring  and  this  latter  in  turn  acts  upon 
the  bent  lever,  and  the  magnified  movement  is  recorded  by  the  writing  point, 
upon  a  strip  of  blackened  paper  which  is  moved 
under  the  point  by  clockwork  contained  in  the 
case.  To  obtain  a  satisfactory  record  or  sphyg- 
mogram,  two  details  are  of  special  importance: 
First,  the  button  of  the  lever  must  be  pressed 
upon  the  artery  with  the  proper  force.  Theo- 
retically this  pressure  should  be  about  equal  to 
the  diastolic  pressure  within  the  artery.  All 
sphygmographs  are  provided  with  means  to 
regulate  the  pressure,  and  practically  one  must 
learn  so  to  place  the  button  and  to  arrange  the 
pressure  as  to  obtain  the  largest  tracing.  A 
second  detail  of  importance  is  that  the  weight 
of  the  lever  when  set  suddenly  into  motion 
causes  a  movement,  due  to  the  inertia  of  the 
mass,  which  may  alter  the  true  form  of  the  wave. 
To  overcome  this  defect  the  lever  should  be  as 
light  as  possible,  or  the  spring  upon  which  the 
artery  plays  should  have  considerable  resis- 
tance. In  those  sphygmographs  in  which  the 
inertia  factor  is  practically  eliminated  the  diffi- 
culty of  obtaining  a  tracing,  especially  from  a 
weak  pulse,  is  correspondingly  increased,  and  in 
the  sphygmographs  most  commonly  employed, 
such  as  the  Dudgeon,  facility  in  application  i> 
obtained  at  the  expense  of  incomplete  correction  of  the  error  of  inertia. 


Fig.  213.— The  lever  of 
the  Dudgeon  sphygmograph : 
P,  The  button  of  the  spring  F, 
to  be  placed  upon  the  artery. 
The  movement  is  transmitted 
to  the  lever,  F\,  and  thence  to 
the  bent  lever,  F2,  whose 
movement  is  effected  through 
the  weight,  g.  The  writing 
point  S,  of  this  lever  makes 
the  record  on  the  smoked  sur- 
face, A. 


The  pulse  wave  obtained  from  the  radial  artery  is  represented 
in  Fig.  214.  It  will  be  seen  from  this  figure  that  the  artery  dilates 
rapidly  and  then  falls  more  slowly,  but  it  must  be  borne  in  mind 
that  the  very  pointed  apex  of  the  wave  recorded  by  this  form  of 
sphygmograph  is  due  to  the  instrumental  error  referred  to  above, 
namely,  the  "fling"  of  the  lever  caused  by  the  sudden  expansion 


Fig.  214.— Sphygmogram  from  the  radial  artery,  Dudgeon  sphygmograph:  D,  The  dicrotic 
wave;  P,  the  predicrotic  wave. 

of  the  artery.  A  more  accurate  record  of  the  radial  pulse  is  shown 
in  Fig.  214a.  The  ascending  portion  of  the  wave  is  spoken  of  as 
the  anacrotic  limb,  the  descending,  as  the  catacrotic  limb.  Under 
usual  conditions  the  anacrotic  limb  is  smooth, — that  is,  shows  no 
secondanr  waves, — while  the  catacrotic  limb  shows  one  or  more 
secondary  waves,  which  are  spoken  of  in  general  as  the  catacrotic 


528  CIRCULATION    OF    BLOOD    AND    LYMPH. 

waves.  The  most  constant  of  these  latter  waves  occurs  usually 
approximately  at  the  middle  of  the  descent  (D)  and  is  designated 
as  the  dicrotic  wave.  A  less  conspicuous  wave  between  it  and  the 


Fig.  214o.— Record  of  the  radial  pulse  taken  with  a  Frank-Fetter  sphygmograph.—l  After  Fetter.) 

apex  of  the  pulse  wave  is  known  usually  as  the  predicrotic  wave,  P, 
while  the  wave  or  waves  following  the  dicrotic  are  designated  as 
postdicrotic.  These  catacrotic  waves  are  too  small,  under  normal 
conditions,  to  be  felt  by  the  finger.  Under  certain  abnormal 
conditions,  however,  which  cause  a  low  blood-pressure  without 
marked  diminution  in  the  heart  beat,  the  dicrotic  wave  is  empha- 
sized and  may  be  detected  by  the  finger.  A  pulse  of  this  kind  is 
known  as  a  dicrotic  pulse.  In  each  pulse  wave  we  may  distinguish 
a  systolic  and  a  diastolic  phase;  the  former,  making  due  allowance 
for  transmission,  corresponds  with  the  time  during  which  the  aortic 
valves  are  open,  and  blood  is  streaming  from  the  heart  to  the  aorta, 
the  latter  represents  the  period  during  which  the  aortic  valves 
are  closed  and  the  arteries  are  shut  off  from  the  heart.  In  Fig.  214 
the  systolic  phase  extends  from  s  to  d,  the  diastolic  from  d  to  s'. 

Explanation  of  the  Catacrotic  Waves. — It  has  been  found 
difficult  to  give  an  entirely  satisfactory  explanation  of  the  catacrotic 
waves  or,  to  speak  more  accurately,  it  is  difficult  to  decide  between 
the  different  explanations  that  have  been  proposed.  Concerning 
the  dicrotic  wave,  it  may  be  said  that  tracings  from  different  ar- 
teries show  that,  like  the  main  pulse  wave,  it  has  a  centrifugal 
course, — that  is,  it  starts  in  the  aorta  and  runs  peripherally  with  the 
same  velocity  as  the  main  wave  upon  which  it  is  superposed.  More- 
over, simultaneous  tracings  of  the  pressure  changes  in  the  heart  and 
in  the  aorta  show  that  the  closure  of  the  semilunar  valves  is  synchro- 
nous with  the  small  depression  or  negative  wave  (d,  Fig.  214)  which 
immediately  precedes  the  dicrotic  wave.  The  general  belief,  there- 
fore, is  that  the  dicrotic  wave  results  from  the  closure  of  the  semi- 
lunar  valves.  When  the  distended  aorta  begins  to  contract  by 
virtue  of  the  elasticity  of  its  walls,  it  drives  the  column  of  blood  in 
both  directions.  Owing  to  the  position  of  the  semilunar  valves 
the  flow  to  the  ventricle  is  prevented;  but  the  interposition  of  this 


THE    PULSE.  529 

sudden  block  causes  a  reflected  wave  which  passes  centrifugally 
over  the  arterial  system.  The  dicrotic  wave  is  preceded  by  a 
small  negative  wave  or  notch  in  the  curve  which  marks  the  time 
of  closure  or  just  follows  the  closure  of  the  semilunar  valves.  The 
sequence  of  events  as  pictured  by  Mackenzie*  is  as  follows:  "As 
soon  as  the  aortic  pressure  rises  above  the  ventricular  the  valves 
close.  At  the  moment  this  happens  the  valves  are  supported  by 
the  hard,  contracted  ventricular  walls.  The  withdrawal  of  the 
support  by  the  sudden  relaxation  of  these  walls  will  tend  to  produce 
a  negative  pressure  wave  in  the  arterial  system.  But  this  negative 
wave  is  stopped  by  the  sudden  stretching  of  the  aortic  valves, 
which,  on  losing  their  firm  support,  have  now  themselves  to  bear 
the  resistance  of  the  arterial  pressure.  This  sudden  checking  of 
the  negative  wave  starts  a  second  positive  wave,  which  is  prop- 
agated through  the  arterial  system  as  the  dicrotic  wave."  The 
smaller  waves,  such  as  the  predicrotic,  have  been  explained 


Fig.  215. — Anacrotic  pulse  from  a  case  of  aortic  stenosis  (Mackenzie):  6,  The  anacrotic 

wave. 

simply  as  reflected  waves,  or  as  instrumental  errors,  due  to  fling 
of  the  lever.  While  the  dicrotic  wave  is  due  primarily  to  the  im- 
pulse following  upon  the  closure  of  the  semilunar  valves,  neverthe- 
less the  actual  form  of  this  and  the  other  secondary  waves  is  va- 
riously modified  in  different  parts  of  the  system  owing  to  imperfect 
transmission  along  the  extensible  arteries  and  to  the  effect  of 
reflected  waves  from  different  peripheral  regions,  f  Wiggers  lays 
stress  upon  the  marked  difference  between  the  central  pulse  as 
recorded  in  the  arteries  near  the  heart  (subclavian  and  lower  car- 
otids) and  the  peripheral  pulse  as  recorded  in  the  radial.  This  dif- 
ference is  shown  in  Fig.  215a,  in  which,  as  explained  in  the  legend, 
the  subclavian  pulse  exhibits  several  significant  pressure  changes 
that  are  lacking  in  the  radial  pulse. 

Anacrotic  Waves. — As  was  said  above,  the  anacrotic  limb 
under  normal  conditions  shows  no  secondary  waves.  Under 
pathological  conditions,  however,  a  secondary  wave  more  or  less 
clearly  marked  may  appear,  as  is  shown,  for  instance,  in  the 
tracing  given  in  Fig.  215.  Such  waves  are  recorded  in  cases  of 

*  Mackenzie,  "The  Study  of  the  Pulse  and  the  Movements  of  the  Heart," 

fFor  a  general  discussion,  see  Tigerstedt,  "Ergebnisse  d.  Physiologic/' 
vol.  viii.,  1909,  and  Wiggers,  "Circulation  in  Health  and  Disease,"  1915. 
34 


530  CIRCULATION    OF    BLOOD    AND    LYMPH. 

stiff  arteries  or  stenosis  of  the  semilunar  valves.  In  the  normal 
individual  an  anacrotic  pulse  in  the  radial  may  be  obtained, 
according  to  von  Kries,*  by  raising  the  arm.  He  believes  that 
in  this  position  the  reflection  of  the  pulse  wave  from  the  periph- 


Fig.  215a.— Photographic  records  of  the  subclavian  (central)  pulse  and  the  radial  (per- 
ipheral) pulse.  On  the  subclavian  pulse,  ab  represents  a  wave  due  to  auricular  systole;  be,  a 
small  wave  due  to  the  rise  of  pressure  in  the  ventricle  before  the  opening  of  the  semilunar 
valves;  cd  marks  the  beginning  of  the  ejection  of  blood  into  the  aorta,  de  representing  a  wave 
due  to  the  vibration  of  the  column  of  blood.  At  g  the  pressure  falls  suddenly  at  the  beginning 
of  diastole  or  relaxation  of  the  ventricle,  giving  the  negative  wave  or  incisura  h;  k,  vibrations 
corresponding  to  the  closure  of  the  semilunar  valves  and  the  second  heart-sound.— (From 
Wiggers.) 

ery  is  favored,  and  that  the  anacrotic  wave  is  simply  a  quickly 
reflected  wave.  An  opposite  interpretation,  however,  is  given 
by  von  Recklinghausen,  who  states  that  conditions  which  lead 
to  a  diminution  in  vascular  tone  and  a  dilation  of  the  arteries 
produce  "weak  reflection"  and  an  anacrotic  pulse.  Constric- 
tion of  the  small  arteries  in  any  system  favors  quick  reflection 
in  the  artery  supplying  the  system  and  produces  a  pulse  with  a 
sharp-pointed  apex. 

Characteristics  of  the  Pulse  in  Health  and  in  Disease. — 
By  mere  palpation  the  physician  obtains  from  the  pulse  valuable 
indications  concerning  the  heart  and  the  circulation.  The  fre- 
quency of  the  heart  beat  is  at  once  made  evident,  so  far  at  least  as 
the  ventricle  is  concerned.  One  may  determine  readily  whether 
the  frequency  is  above  or  below  the  normal,  whether  the  rhythm 

*  Von  Kries,  "Studien  zur  Pulslehre,"  1892. 


THE    PULSE.  531 

is  regular  or  irregular.  By  the  same  means  one  can  determine 
whether  the  pulse  is  large  (pulsus  magnus)  or  small  (pulsus  par- 
vus),  whether  the  wave  rises  and  falls  rapidly  (pulsus  celer)  as  hap- 
pens in  the  case  of  insufficiency  of  the  aortic  valves,  or  whether  in 
one  phase  or  the  other  it  is  more  prolonged  than  normal  (pulsus  tar- 
dus).  It  seems  obvious,  however,  that  a  more  satisfactory  conclu- 
sion may  be  reached  in  all  such  cases  by  obtaining  a  sphygmographic 
record,  although,  as  previously  intimated,  the  details  of  such  tracings 
as  obtained  from  most  forms  of  sphygmographs  have  come  under 
suspicion  on  account  of  instrumental  errors  in  the  recording  ap- 
paratus. By  mere  pressure  upon  the  artery  one  can  deter- 
mine also  approximately  whether  the  blood-pressure  is  high  or 
low  by  estimating  the  force  with  which  the  wave  presses  upon 


Fig.  216. — Sphygmograms  illustrating  the  effect  of  variations  in  blood-pressure,  partic- 
ularly upon  the  position  of  the  dicrotic  wave  and  notch  :  n,  The  dicrotic  notch ;  d,  the 
dicrotic  wave.  A,  Sphygmogram  while  blood-pressure  was  relatively  low.  B,  Sphygmo- 
gram  with  higher  blood-pressure.  (Mackenzie.) 

the  fingers,  or  the  pressure  necessary  to  occlude  the  artery.  A 
similar  inference  may  be  drawn  from  the  character  of  the  sphyg- 
mogram,  and  especially  from  the  relative  size  and  position  of  the 
dicrotic  wave.  When  this  latter  wave  falls  at  or  near  the  base  line 
of  the  curve  it  indicates  a  low  arterial  pressure,  since  under  these 
circumstances  the  artery  collapses  readily  after  its  first  systolic 
expansion  (see  Fig.  216).  Since  the  introduction  of  the  sphyg- 
momanometer  (p.  503),  however,  it  seems  evident  that  this  instru- 
ment must  be  appealed  to  whenever  the  determination  of  blood- 
pressure  is  a  matter  of  importance. 

Venous  Pulse. — Under  usual  conditions  the  pulse  wave  is  lost 


532  CIRCULATION    OF    BLOOD    AND    LYMPH. 

before  entering  the  capillary  regions,  but  as  a  result  of  dilatation  in 
the  arteries  of  an  organ  the  pulse  may  carry  through  and  appear  in 
the  veins,  in  which  it  may  be  shown,  for  instance,  by  the  rhythmical 
flow  of  .blood  from  an  opened  vein.  The  term  venous  pulse,  how- 
ever, as  generally  used  applies  to  an  entirely  different  phenomenon, 
— namely,  to  a  pulse  observed  especially  in  the  large  veins  (jugular) 
near  the  heart.  The  pulse  in  this  case  is  not  due  to  a  pressure  wave 
transmitted  through  the  capillaries,  but  to  pressure  changes  t  of 
both  a  positive  and  negative  character  occurring  in  the  heart  or 
the  neighboring  arteries  and  transmitted  to  the  veins.  The  venous 
pulse  that  has  this  origin  may  usually  be  seen  and  recorded  in  the 
external  (or  internal)  jugular.  Under  pathological  conditions,  espe- 
cially when  the  flow  through  the  right  heart  is  more  or  less  impeded, 
it  may  be  plainly  apparent  at  a  further  distance  from  the  heart  and 
may  cause  a  noticeable  pulsation  of  the  liver,  which  is  designated  as 
a  liver  pulse.  The  venous  pulse  curve  has  been  much  studied  in 
recent  years.*  It  is  somewhat  complicated  and  an  explanation 
of  some  of  its  details  has  not  been  agreed  upon,  but  there  can  be  no 
doubt  that  when  properly  interpreted  it  will  throw  much  light  upon 
the  pressure  changes  in  the  heart,  and  will  afford  a  valuable  means 
of  diagnosis  in  cases  of  valvular  lesions  and  other  pathological 
conditions  of  the  heart.  It  is  evident  also  that  the  venous  pulse 
gives  a  ready  means  of  determining  the  rate  of  beat  of  the  auricles, 
just  as  the  arterial  pulse  enables  us  to  count  the  beats  of  the  ven- 
tricles, and  in  this  way  records  of  the  venous  pulse  are  important 
in  the  interpretation  of  irregularities  in  the  beat  of  the  heart 
(arrhythmia). 

As  usually  recorded  the  venous  pulse  shows  three  positive 
waves,  designated  commonly  as  the  a,  c,  and  v  waves,  and  three 
negative  waves.  Of  the  three  positive  waves,  the  a  wave  marks, 
undoubtedly,  the  contraction  of  the  auricle,  but  in  order  to 
locate  this  wave  or,  indeed,  to  interpret  at  all  the  complicated 
venous  pulse,  it  is  necessary  to  have  a  simultaneous  tracing  of 
the  arterial  pulse,  preferably  the  carotid,  or  of  the  apex  beat  of 
the  heart.  Either  of  these  latter  tracings  enables  one  to  mark 
upon  the  venous  pulse  the  point  at  which  the  ventricular  systole 
begins,  and  the  wave  immediately  preceding  this  point  must 
be  due  to  the  auricular  contraction,  the  a  wave  (Figs.  217  and 
218).  Following  the  rise  of  the  a  wave  there  is  a  fall,  the  first 
negative  wave,  which  is  due  to  the  auricular  relaxation.  The 
interpretation  of  the  other  two  positive  and  negative  waves 
has  been  the  subject  of  much  discussion.  Mackenzie,  one  of 
whose  tracings  is  reproduced  in  Fig.  217),  believed  that  the 

*See  Mackenzie,  "  The  Study  of  the  Pulse,"  1902;  also  Lewis,  in  Hill's 
"  Further  Advances  in  Physiology,"  New  York,  1909. 


THE    PULSE.  533 

c  wave  is  due  simply  to  the  pulse  in  the  underlying  carotid  or 
subclavian  artery,  and  that,  therefore,  it  has  no  special  significance 
in  regard  to  changes  within  the  auricle  itself.  Discussions  in  re- 
gard to  the  meaning  of  this  wave  have  turned  largely  upon  its  time 
relations  to  the  pulse  wave  in  the  neighboring  arteries.  Some  ob- 
servers have  obtained  records  which  seem  to  show  that  the  c  wave 
begins  in  the  jugular  before  a  pulse  wave  appears  in  the  carotid  at 
thjB  same  level,  as  is  shown,  for  example,  in  the  tracings  reproduced 
in  Fig.  218.  The  more  sensitive  and  probably  more  reliable  optical 
methods  of  recording  indicate,  however,  that  the  c  wave  appears 
exactly  at  the  time  of  the  pulse  in  the  subclavian  artery,*  a  fact 
which  would  justify  Mackenzie's  view  that  this  wave  is  due  to  im- 
pact from  the  neighboring  arteries.  Measurements  made  in  the 
auricle  itself  reveal  a  positive  wave  occurring  at  the  beginning  of 


Carotid 


J  \rv 


^  %f 

R*  Int.  Jugular 


Fig.  217. — Simultaneous  tracings  of  the  carotid  and  venous  pulses.  In  the  venous 
tracing  (internal  jugular)  a  indicates  the  auricular  wave  due  to  the  contraction  of  the  auri- 
cle; c  is  the  carotid  wave  due  (Mackenzie)  to  an  impulse  from  the  neighboring  carotid 
artery;  v  is  the  ventricular  wave  due  to  the  checking  or  stagnation  of  the  flow  into  the 
auricle  as  this  chamber  fills  during  the  period  of  closure  of  the  auriculo ventricular  valves. 
— (Mackenzie.) 

ventricular  systole  and  explained  as  due  to  a  protrusion  of  the 
closed  auriculo  ventricular  valves  toward  the  auricle  as  the  pressure 
rises  in  the  contracting  ventricle.  If  this  auricular  positive  wave 
is  transmitted  back  to  the  jugular  vein  it  may  enter  as  a  factor  in 
the  production  of  the  c  wave  as  usually  recorded.  Following  the 
c  wave  is  a  second  negative  wave,  usually  quite  marked,  which 
occurs  during  the  period  of  systolic  output  of  blood  from  the  ven- 
tricles. It  has  been  explained  as  due  to  the  shortening  of  the 
ventricle  from  base  to  apex,  resulting  in  a  downward  movement  of 
the  closed  auriculo  ventricular  valves.  The  sudden  forcible  pulling 
down  of  the  floor  of  the  auricle  would  tend  to  lower  intra-auricular 
pressure,  and  the  negative  wave  thus  produced  if  transmitted  back 
to  the  jugular  vein  would  coincide  in  time  with  the  fall  in  pressure 
following  the  c  wave.  This  negative  wave  is  converted  into  a  posi- 
tive wave  by  the  steady  inflow  of  venous  blood -,  which  continues  to 
*  Wiggers,  loc.  cit. 


534  CIRCULATION    OF    BLOOD    AND    LYMPH. 

pour  into  the  auricle  during  the  whole  period  of  the  systole  of  the 
ventricle  and  of  the  closure  of  the  auriculo ventricular  valves. 
In  this  way  the  wave  v  is  produced.  It  is  frequently  of  irregular 
or  toothed  form  and  rises  somewhat  gradually  to  its  maximum. 
The  end  or  maximum  of  the  wave  falls  in  with  the  beginning 
of  the  muscular  relaxation  of  the  ventricle,  and  the  return,  there- 
fore, of  the  base  of  the  ventricle  to  its  diastolic  position.  Im- 
mediately afterward  the  auriculoventricular  valves  open,  and  the 
blood  accumulated  in  the  auricles  is  discharged  into  the  ventricle, 


Fig.  218. — Simultaneous  tracings  of  the  jugular  pulse,  the  carotid  pulse,  and  the 
apex  beat.  (Bachmann.)  At  the  bottom  of  the  tracing  the  time  is  given  in  fiftieths  of 
a  second.  The  vertical  lines  0,  1,  2,  3,  etc.,  mark  synchronous  points  on  the  curves. 
A,  The  auricular  wave;  s,  the  so-called  c  wave  caused  by  the  systole  of  the  ventricle;  v,  the 
stagnation  wave  caused  by  the  filling  of  the  auricle.  It  will  be  noticed  that  the  c  wave 
(marked  s  in  the  tracing)  occurs  at  the  beginning  of  the  ventricular  systole  as  marked  on 
the  apex  beat,  and  shortly  before  the  pulse  in  the  carotid  artery.  The  height  of  the  v  wave 
is  reached  just  after  the  occurrence  of  the  dicrotic  notch  on  the  carotid  wave,  and  coin- 
cides with  the  opening  of  the  auriculoventricular  valves;  Af,  the  negative  wave  caused  by 
the  effect  of  the  ventricular  systole;  Vf,  the  negative  wave  following  the  opening  of  the 
auriculoventricular  valves. 

causing  again  a  sudden  fall  of  pressure  in  the  auricles  and  veins,  the 
third  negative  wave. 

One  view  of  the  relation  of  the  different  venous  waves  to  the 
sequence  of  events  in  the  ventricle  and  aorta  is  shown  in  the 
diagram  given  by  Fredericq,  which  is  reproduced  in  Fig.  219. 
Following  this  author,*  the  series  of  positive  and  negative  waves 
which  may  usually  be  shown  in  the  auricles  and  great  veins  during 
a  single  heart  beat  may  be  enumerated  as  follows  : 

1.  The  auricular  wave  (a  wave),  auricular  systole. 

*  Fredericq,  " Centralblatt  f.  Physiol.,"  22,  No.  10,  1908. 


THE    PULSE. 


535 


2.  The  first  negative  wave,  auricular  diastole. 

3.  First  systolic  wave  (positive),  c  wave.     Beginning  of  ven- 
tricular systole.    Due  to  sudden  closure  and  protrusion  of  the  au- 
riculo ventricular  valves  (or  to  impact  of  the  underlying  arteries). 


Fig.  219. — Schema  of  the  variations  of  pressure  in  the  ventricle,  auricle,  aorta,  and 
superior  vena  cava  during  a  cardiac  cycle  in  the  dog :  a,  6,  Systole  of  the  auricle;  6,  c,  d,  e, 
systole  of  the  ventricle ;  &',  opening  of  the  semilunar  valves ;  e,  closure  of  the  semilunar 
valves  ;  6,  6',  closure  of  the  auriculoventricular  valves  ;  f ,  opening  of  the  auriculoventricular 
valves.  On  the  curve  for  the  auricle  and  vein  the  wave  from  a  to  6  represents  the  auricular 
contraction,  the  a  wave;  that  beginning  at  6  is  the  wave  due  to  ventricular  systole,  the 
c  wave,  and  the  rise  of  pressure  extending  from  d  to  e  and  ending  with  the  opening  of  the 
auriculoventricular  valves  constitutes  the  v  wave.  The  time  relations  are  given  along  the 
abscissa  in  tenths  of  a  second,  the  pressure  relations  in  mms.  of  mercury  for  the  ventricle 
and  aorta  are  given  along  the  ordinates  to  the  left.  (After  Fredericq.) 

4.  Second  negative  wave.     At  the  time  of  opening  of  the  semi- 
lunar  valves.     Due  to  descent  of  the  base  of  the  ventricle,  causing 
dilatation  of  auricle. 

5.  Second  systolic  wave  (positive),  v  wave.     Latter  part  of 
systole.     Due  to  gradual  filling  of  auricle  and  at  the  end  to  the 
return  of  the  base  of  the  ventricle  to  its  diastolic  position. 

6.  Postsystolic  (third)  negative  wave  begins  at  moment  of 
opening  of  the  a-v  valves.     Due  to  emptying  of  auricular  blood 
into  ventricle. 

Other  waves  have  been  described,  especially  one  in  the  dias- 
tolic phase  of  the  ventricular  beat,  which  is  known  as  the  h  wave 
(Hirschf elder)  or  b  wave  (Gibson).  This  wave  occurs  between 
the  v  and  the  a  wave  and  is  seen  most  frequently  and  distinctly  in 


536  CIRCULATION    OF    BLOOD    AND    LYMPH. 

the  case  of  hearts  with  a  slow  rate  of  beat.  The  usual  explanation 
of  this  wave  is  that  it  is  due  to  the  very  sudden  distention  of  the 
ventricles  by  the  inflowing  blood.  The  rise  in  intra ventricular 
pressure  thus  produced  brings  the  auriculoventricular  valves 
suddenly  into  a  position  of  closure  and  causes  a  momentary  posi- 
tive wave  in  the  auricles  and  great  veins.  For  the  variations  in 
the  form  of  the  venous  pulse  under  pathological  conditions  of  the 
heart,  reference  must  be  made  to  clinical  literature.* 

*  See  Hewlett,  "Journal  of  Medical  Research,"  17,  1907;  "Journal  of 
the  Amer.  Med.  Asspc.,"  51,  1908,  and  Hirschfelder,  "Diseases  of  the 
Heart  and  Aorta,"  Philadelphia,  1910. 


CHAPTER  XXVIII. 
THE  HEART  BEAT. 

General  Statement. — We  divide  the  heart  into  four  chambers, 
— the  two  auricles  and  the  two  ventricles.  What  we  designate  as  a 
heart  beat  begins  with  the  .simultaneous  contraction  of  the  two 
auricles,  immediately  followed  by  the  simultaneous  contraction  of 
the  two  ventricles;  then  there  is  a  pause,  during  which  the  whole 
heart  is  at  rest  and  is  filling  with  blood.  As  a  matter  of  fact,  the 
heart-beat  is  initiated  not  by  the  auricles  proper,  but  by  an  area 
of  specialized  tissue  in  the  right  auricle  lying  between  the  open- 
ings of  the  two  cavse.  This  portion  of  the  auricular  wall  corre- 
sponds physiologically  to  a  definite  chamber,  the  venous  sinus, 


Fig.  220. — To  show  the  time  relations  of  the  auricular  systole  and  diastole,  and  ven- 
tricular systole  and  diastole  (Marey) :  Or.  D,  Tracing  from  right  auricle ;  Vent.  D,  tracing 
from  right  ventricle;  Vent.  G,  tracing  from  left  ventricle.  Obtained  from  the  heart  of  the 
horse  by  means  of  tubes  communicating  with  the  cavities. 

in  the  heart  of  the  lower  vertebrates  (see  Fig.  224) .  The  contrac- 
tion of  any  part  of  the  heart  is  designated  as  its  systole,  its  relaxa- 
tion and  period  of  rest  as  its  diastole.  In  the  heart-beat  we  have, 
therefore,  the  auricular  systole,  the  ventricular  systole,  and  the 
heart  pause,  during  which  both  chambers  are  in  diastole.  The 
general  relations  of  systole,  diastole,  and  pause  are  represented 
graphically  in  the  accompanying  figure  (Fig.  220).  It  will  be 
noted  that  the  auricular  systole  is  shorter  and  its  diastole  longer 
than  the  similar  conditions  in  the  ventricles. 

The  Musculature  of  the  Auricles  and  Ventricles. — Embryo- 

537 


538 


CIRCULATION    OF    BLOOD    AND    LYMPH. 


logically  the  four-chambered  heart  is  developed  from  a  simple 
tube,  and  this  origin  is  indicated  in  the  adult  by  the  fact  that  the 
musculature  of  the  two  auricles  is  in  large  part  common  to  both 
chambers, — that  is,  surrounds  them  as  though  they  were  a  single 
chamber, — and  the  same  is  true  of  the  ventricles.  In  the  auricles 
there  is  a  superficial  layer  of  fibers  which  runs  transversely  and  en- 
circles both  auricles.  The  simultaneous  contraction  of  the  two 
chambers  would  seem  to  be  insured  by  this  arrangement  alone. 
In  addition,  each  auricle  possesses  a  more  or  less  independent 
system  of  fibers,  whose  course  is  at  right  angles  to  that  of  the 


Fig.  221. — Schema  to  show  the  course  of  the  superficial  and  deep  fibers  of  the  bulbo- 
spiral  and  sinospiral  systems.  The  heart  is  viewed  from  the  dorsal  side.  BS,  superficial  bulbo- 
spiral  system;  BS',  deep  bulbospiral  system;  SS,  superficial  sinospiral  system;  SS',  deep  sino- 
spiral system;  C,  circular  fibers  round  the  conus;  C",  circular  fibers  round  the  base  of  the  aorta 
and  the  left  ostium;  LRV,  longitudinal  bundle  of  right  ventricle,  from  membranous  septum  to 
right  ventricle;  IV,  interventricular  or  interpapillary  layer  (Mall). 

preceding  layer.  These  fibers  may  be  considered  as  loops  arising 
and  ending  in  the  auriculo-ventricular  ring.  The  course  of  the 
fibers  in  the  ventricles  has  been  difficult  to  make  out,  and  several 
more  or  less  different  accounts  have  been  published.  The  fibers 
on  the  surface  of  the  heart  arise  from  the  tendinous  rings  and  mem- 
branes at  the  base  and  take  a  spiral  course  to  the  apex,  where  they 
form  a  vortex  and  pass  into  the  interior  of  the  left  ventricle  to  enter 
the  septum  and  make  connections  with  the  papillary  muscles. 
In  this  way  they  return  upon  themselves  toward  the  base  of  the 
heart  and  form  spiral  loops  whose  contractions  serve  to  approxi- 


THE    HEART    BEAT.  539 

mate  base  and  apex  and  at  the  same  time  to  give  a  rotation  to  the 
apex  from  left  to  right.  Mall*  divides  these  superficial  fibers  into 
two  groups.  First,  the  superficial  bulbo-spiral  fibers  (B  S)  which 
arise  from  the  conus,  the  left  side  of  the  aorta,  and  the  left  side  of 
the  left  ostium  venosum,  take  a  spiral  course  to  the  apex,  where 
they  form  the  posterior  horn  of  the  vortex,  and  penetrate  to  the 
interior  of  the  left  ventricle  to  end  in  the  septum  and  along  the 
posterior  side  of  the  ventricle,  making  connections  also  with  the 
posterior  papillary  muscle.  Some  of  the  deeper  fibers  of  this 
layer  encircle  the  lower  part  of  the  ventricle  and  then  pass  upward 
to  end  at  the  base  of  the  heart.  The  bulbospiral  fibers  belong 
chiefly  to  the  left  ventricle.  Second,  the  superficial  sinospiral 


Fig.  222 — Anterior  surface  of  the  heart,  to  show  the  arrangement  of  the  superficial  fibers 
over  the  right  ventricle:  SS,  Sinospiral  band;  BS,  bulbospiral  band;  B,  C,  fibers  of  the  bulbo- 
TOiral  system  as  they  enter  the  vortex;  D,  E,  fibers  of  the  sinospiral  band  as  they  enter  the  vortex 

fibers  (S  $),  which  arise  mostly  on  the  posterior  aspect  of  the  heart 
from  the  right  ostium  venosum,  the  sinus  end  of  the  embryonic 
heart,  take  a  spiral  course  to  the  apex  over  the  anterior  surface  of 
the  right  ventricle,  running  more  transversely  than  the  bulbo- 
spiral group.  At  the  vortex  this  system  forms  the  anterior  horn 
of  the  vortex  and  penetrates  into  the  interior  of  the  left  ventricle, 
to  end  along  the  anterior  side  and  in  the  papillary  muscles,  par- 
ticularly the  anterior  papillary.  Beneath  these  superficial  layers 
lie  corresponding  deep  layers  of  the  bulbospiral  and  sinospiral 
systems,  which  have  a  more  transverse  or  circular  course.  The 
deep  bulbospiral  fibers  (B  S')  encircle  the  left  ventricle  and  end 

*  Mall,  "The  American  Journal  of  Anatomy,"  2,  211,  1911. 


540  CIRCULATION    OF    BLOOD    AND    LYMPH. 

by  way  of  the  septum  on  the  dorsal  side  of  the  aorta.  These 
fibers  in  the  developed  heart  make  a  strong  circular  system  whose 
contraction  tends  to  diminish  the  lumen  of  the  left  ventricle. 
Below  the  superficial  sinospiral  system  lies  the  deep  sinospiral 
sheet  (S  S'),  which  arises  from  the  posterior  side  of  the  left  ostium 
and  passes  transversely  to  enter  the  interior  of  the  right  ventricle 
and  then  turn  upward  toward  the  base.  At  the  base  of  the  heart 
some  of  the  fibers  of  the  bulbospiral  system  pass  circularly  round 
the  base  of  the  aorta  and  the  left  ostium,  and  in  the  right  ventricle 
some  of  the  sinospiral  system  form  circular  loops  round  the  conus 
at  the  base  of  the  pulmonary  artery. 


/CIV 


Fig.  223. — Posterior  view  of  heart,  somewhat  to  left,  after  the  superficial  sinospiral  band 
has  been  removed  to  the  posterior  longitudinal  sulcus:  BS',  deep  bulbospiral  band;  BS,  super- 
ficial bulbospiral  band,  A,  B,  and  C  are  fibers  belonging  to  this  system  and  forming  the  posterior 
horn  of  the  vortex ;  SS,  superficial  sinospiral  band,  D  and  E  are  fibers  belonging  to  this  system 
and  forming  the  anterior  horn  of  the  vortex ;  CL  V,  the  circular  band  (bulbospiral  system)  round 
the  left  venous  ostium  (Mall). 

The  Auriculoventricular  Bundle. — A  matter  of  very  great 
physiological  interest  in  connection  with  the  invariable  sequence 
of  the  heart-beat  has  been  the  question  of  the  existence  of  a  direct 
muscular  connection  between  the  auricles  and  ventricles.  In 
the  lower  vertebrates  there  is  muscular  continuity  throughout 
the  heart  from  the  venous  end  to  the  arterial  end.  In  hearts  of 
this  type  (see  Fig.  224)  we  may  distinguish  four  different  chambers — 
the  sinus  venosus,  into  which  the  great  veins  open,  the  auricle 
(right  and  left),  the  ventricle  (single),  and  the  bulbus  arteriosus 
or  bulbus  cordis.  The  musculature  of  each  chamber  connects 
with  that  of  the  succeeding  one,  and  the  contraction  wave,  which 
begins  in  the  sinus,  spreads  in  order  to  the  following  divisions  of 


THE    HEART    BEAT.  541 

the  heart.  There  is,  however,  a  pause  or  interruption  in  the  pas- 
sage of  this  wave  at  the  sino-auricular  junction,  at  the  auriculo- 
ventricular  junction,  and  at  the  bulbo ventricular  junction,  so  that 
the  contraction  of  each  chamber  is  marked  off  as  a  separate  oc- 
currence. In  the  human  heart  and  the  mammalian  heart  in 
general  we  are  accustomed  to  distinguish  only  the  auricles  and 
ventricles,  but  physiological  and  anatomical  studies  combined 
have  shown  that  in  such  hearts  a  remnant  of  the  sinus  venosus  is 


Fig.  224. — A  generalized  type  of  vertebrate  heart,  combining  features  found  in  the  eel, 
dogfish  and  frog  (Keith):  a,  Sinus  venosus  and  veins;  b,  auricular  canal;  c,  auricle;  d,  ventricle; 
e,  bulbus  cordis;/,  aorta;  1-1,  sino-auricular  junction  and  venous  valves;  2-2,  canalo-auricular 
junction;  3-3,  annular  part  of  auricle;  4-4,  invaginated  part  of  auricle;  5,  bulboventricular 
junction. 

found  in  the  right  auricle,  particularly  in  the  area  lying  between 
the  openings  of  the  venae  cavse  and  round  the  coronary  sinus.  A 
special  collection  of  this  tissue  which  lies  "  in  the  sulcus  terminalis 
just  below  the  fork  formed  between  the  junction  of  the  upper  sur- 
face of  the  auricular  appendix  with  the  superior  vena  cava"  has 
been  described  by  Keith  and  Flack,  and  is  designated  as  the  sino- 
auricular  node.  The  beat  of  the  heart  begins  in  this  tissue,  as  in 
the  case  of  the  hearts  of  the  lower  vertebrates,  and  spreads  directly 
to  the  auricular  muscle.  The  matter  of  greatest  interest  in  con-< 
nection  with  the  different  chambers  has  been  the  nature  of  the  auric- 
ulo ventricular  junction.  In  the  mammalian  heart  tendinous  tissue 
develops  in  this  region,  and  for  a  long  time  it  was  supposed  that 
there  was  no  muscular  connection  between  auricles  and  ventricles. 
In  recent  years,  however,  it  has  been  shown  most  satisfactorily  that 
there  is  a  peculiar  band  of  cardiac  muscle  or  modified  muscle,  known 
usually  as  the  auriculoventricular  bundle,  which  connects  auricle  and 


542  CIRCULATION    OF    BLOOD    AND    LYMPH. 

ventricle.*  The  bundle  as  a  definite  structure  begins  at  the  base  of 
the  interauricular  septum,  at  the  posterior  margin,  and  on  the 
right  side  in  a  collection  of  small  cells  or  fibers  known  as  the  node, 
or  the  auriculoventricular  node  (A-V  node),  it  runs  as  a  bundle  along 
the  top  of  the  interventricular  septum  (see  Fig.  225),  and  near  the 
union  of  the  posterior  and  median  flaps  of  the  aortic  valve  it 
divides  into  two  main  branches,  one  of  which  enters  the  right 
ventricle,  the  other  the  left,  each  lying  beneath  the  endocardium. 
Passing^  down  the  septal  wall,  these  branches  divide,  f  as  repre- 
sented in  Fig.  226,  to  form  a  system  of  strands  that  can  be  traced 
over  the  inner  surface  of  the  ventricles,  constituting  what  were 


Fig.  225. — To  show  the  position  of  the  auriculoventricular  bundle  in  the  heart  of  the  calf: 
2,  The  auriculoventricular  bundle.  As  it  runs  along  the  top  of  the  ventricular  septum,  it  is 
seen  to  divide  into  two  branches,  one  entering  the  right,  the  other  the  left,  ventricle;  3,  the  begin- 
ning of  the  bundle  in  the  auricular  septum  known  as  the  A-V  node;  4,  the  branch  of  the  bundle 
entering  the  right  ventricle  in  the  septal  wall;  1,  central  cartilage  (from  Keith). 

formerly  designated  as  Purkinje  fibers.  The  auriculoventricular 
node  in  the  interauricular  septum  is  connected  with  the  muscula- 
ture of  the  auricles,  and  through  muscle  bundles  in  the  septum  with 
the  remnant  of  sinus  tissue  (sino-auricular  node)  at  the  mouth  of 
the  superior  vena  cava.  The  main  bundle  and  the  larger  branches 
of  this  system  are  surrounded  by  fibrous  tissue,  and  it  is  uncer- 
tain whether  or  not  they  actually  contract  during  the  beat  of  the 

*  See  Retzer,  " Archiv  f.  Anatomic,"  1904,  p.  1,  and  "Anatomical  Record," 
2,  149,  1908;  Braeunig,  "Archiv  f.  Physiologic,"  1904,  suppl.  volume,  p.  1; 
Tawara,  "Das  Reizleitungssystem  des  Saugethierherzens,"  Jena,  1906. 

t  DeWitt,  "Anatomical  Record,"  3,  475,  1909. 


THE    HEART    BEAT.  543 

heart,  but  there  is  little  doubt  that  they  constitute  a  conducting 
system  of  modified  muscular  tissue  through  which  the  excitation  is 
conveyed  from  auricle  to  ventricle,  or  perhaps,  more  correctly 
speaking,  from  the  auriculoventricular  node  to  the  ventricular 
musculature.  The  contraction  wave  of  the  auricle  is  not  trans- 
mitted directly  to  the  ventricle,  but  indirectly  through  the  con- 
ducting system,  the  A-V  bundle.  Some  authors*  believe,  in 
fact,  that  the  excitation  process  which  originates  in  the  sino- 
auricular  node  spreads  independently  to  the  auricular  muscle, 
on  the  one  hand,  and  to  the  ventricular  muscle  on  the  other.  The 
path  in  the  latter  case  is  firsi  to  the  auriculoventricular  node,  and 
thence  through  the  auriculoventricular  bundle  to  the  interior  of 
the  ventricles  (papillary  muscles).  The  A-V  node  and  the  main 
bundle  in  the  human  heart  are  small  in  size — about  18  mm.  long, 
and  from  1.5  to  2.5  mm.  wide,  and  they  and  their  dependent 
system  of  fibers  or  strands  in  the  interior  of  the  ventricles  con- 
stitute, according  to  Keith  and  Flack,  f  a  remnant  of  the  original 


Fig.  226. — The  auriculoventricular  bundle  and  its  terminal  ramifications  in  the  interior 
of  the  ventricles  (from  model  constructed  by  Miss  De  Witt  on  basis  of  dissections).  The  divi- 
sion of  the  bundle  into  right  and  left  branches  is  shown,  and  the  ramifications  of  each  of  these 
branches  in  the  interior  of  the  right  and  left  ventricles.  The  branching  system  in  the  left  ven- 
tricle is  incomplete  in  the  model,  as  the  outer  wall  of  this  ventricle  had  been  removed  in  the 
dissection. 

invagination  of  muscular  tissue  from  the  auricular  ring  (Fig.  224), 
through  which  auricle  and  ventricle  are  connected  in  the  lower 
vertebrates.  In  addition  to  the  auriculoventricular  bundle  Kent 
describes  two  other  connections  between  auricles  and  ventricles. 
The  more  important  of  these  lies  on  the  right  side  of  the  heart,  and 

*  Eyster  and  Meek,  "Heart,"  15,  119,  914. 

t  Keith  and  Flack,  "  Journal  of  Anat.  and  Physiology,"  41,  172,  1906,  and 
43,  p.  1. 


544  CIRCULATION    OF    BLOOD    AND    LYMPH. 

consists  of  a  mass  of  nodal  tissue  lying  in  the  wall  of  the  right 
auricle  and  possessing  connections  with  the  musculature  of  the 
right  auricle  and  the  right  ventricle.  When  all  parts  of  the  auriculo- 
ventricular  groove  (including  the  A-V  bundle)  are  severed,  except 
the  right  lateral  wall  at  the  location  of  this  bundle  of  Kent,*  beats 
originating  in  the  auricle  are  transmitted  to  the  ventricle  in  due 
sequence.  It  seems  probable  that  this  additional  connection 
between  auricle  and  ventricle,  designated  as  the  right  lateral 
connection,  may  play  some  role,  as  yet  undetermined,  in  the 
maintenance  of  the  sequence  of  the  heart  beat. 

The  Sequence  of  the  Heart  Beat. — In  the  rhythmic  heart  beat 
it  is  believed  that  an  excitation  or  impulse  arises  first  in  the  sino- 
auricular  node  and  thence  spreads  over  the  heart  in  the  form  of  a 
wave  or  pulse.  The  wave  of  excitation  is  followed  by  a  wave  of 
contraction.  That  the  excitation  starts  in  the  sino-auricular  node 
is  indicated  by  the  fact  that  the  first  appearance  of  negativity, 
as  detected  by  the  galvanometer  (see  following  paragraph),  occurs 
at  this  point,  and  by  the  further  fact  that  cooling  in  this  region 
slows  the  rhythm  of  the  heart-beat,  while  variations  in  tempera- 
ture elsewhere  are  without  effect.  Direct  efforts  to  demonstrate 
this  function  of  the  S-A  node  by  the  method  of  extirpation  have 
given  conflicting  results.  The  course  of  the  wave  of  excitation 
from  the  S-A  node  over  the  heart  has  been  studied  in  various  ways, 
but  with  not  wholly  concordant  results.  According  to  a  recent 
summary  given  by  Lewis,  f  and  based  largely  on  his  own  work,  the 
sequence  of  events  is  as  follows:  The  excitation  starts  in  the  S-A 
node,  which  possesses  the  highest  rhythmicity  of  any  part  of  the 
heart,  and  serves,  therefore,  to  use  a  figurative  expression,  as  its 
pace-maker.  From  the  S-A  node  the  excitation  spreads  in  a  uni- 
form manner  over  the  auricles,  traveling  with  a  velocity  of  about 
1000  mms.  per  second,  and  the  following  contraction  takes  the 
form  of  a  rapidly  moving  peristaltic  wave  which  forces  blood  toward 
the  ventricle.  The  contraction  spreads  backward  also  for  some 
distance  along  the  cavse  and  the  pulmonary  veins.  The  excitation 
or  impulse  reaches  the  auriculo-ventricular  node  through  the  auric- 
ular musculature,  and  in  the  node  suffers  some  delay,  owing  prob- 
ably to  the  slower  rate  of  conduction  exhibited  by  this  tissue.  It 
is  this  delay  at  this  point  which  causes  mainly  the  perceptible 
interval  between  the  auricular  and  the  ventricular  contraction. 
From  the  A-V  node  the  excitation  is  conveyed  to  the  ventricle 
through  the  conducting  system,  that  is,  the  auriculo ventricular 
bundle  and  its  ramifications  over  the  internal  surface  of  the  two 

*  Kent,  "Proceedings  of  the  Royal  Society,"  B.  87, 198, 1914,  and"  Journal 
of  Physiology,"  48,  1914,  "Proc.  Physiol.  Soc." 

t  Lewis,  Croonian  Lecture,  "Proceedings  of  the  Royal  Society,"  London, 
B.  89,  560,  1917;  also  "Harvey  Lectures,"  1914-15. 


THE    HEART    BEAT.  545 

ventricles.  In  this  tissue  the  conduction  is  very  rapid,  about  3000 
to  5000  mms.  per  second.  By  means  of  this  system  of  so-called 
Purkinje  fibers  the  excitation  is  distributed  nearly  uniformly  to  the 
musculature  of  the  two  ventricles.  It  was  the  older  view  that  the 
excitation  and  contraction  reached  first  some  definite  region  and 
thence  followed  the  anatomical  course  of  the  fibers,  but  according 
to  Lewis  the  excitation  is  conveyed  by  the  conducting  system  almost 
simultaneously  to  the  whole  of  the  interior  surfaces  of  the  ven- 
tricles, and  at  each  point  radiates  out  through  the  muscular  mass 
toward  the  external  surface.  ,  The  result  is  that  the  whole  mass  of 
the  musculature  contracts  practically  at  once,  although  careful 
galvanometric  examination  of  the  external  surface  by  the  method 
referred  to  in  the  next  paragraph  reveals  that  the  excitation  reaches 
the  surface  first  where  the  musculature  is  thinnest  or  is  connected 
most  directly  with  the  A-V  bundle. 

The  Electrical  Variation. — The  contraction  of  the  heart  mus- 
cle, like  that  of  skeletal  muscle,  is  accompanied  or  preceded  by 
an  electrical  change.  That  is,  where  the  muscle  substance  is  in 
contraction  its  electrical  potential  is  different  from  that  of  the 
resting  muscle.  The  advancing  wave  of  contraction  causes  a 
corresponding  electrical  change  or,  to  be  more  accurate,  the  ad- 
vancing wave  of  excitation,  which  precedes  the  actual  contraction, 
is  accompanied  by  an  electrical  change.  If  two  points  of  the  heart 
are  connected  with  an  electrometer  an  electrical  current  will  be 
shown,  since  the  electrical  change  will  affect  the  electrodes  at 
different  times.  This  electrical  variation  of  the  contracting  heart 
muscle  may  be  shown  easily  by  means  of  the  rheoscopic  muscle- 
nerve  preparation  (see  p.  104).  If  the  heart  is  exposed  and  the 
nerve  of  the  preparation  is  laid  over  its  surface  each  ventricular 
systole  is  accompanied  by  a  kick  of  the  muscle,  since  the  nerve  by 
connecting  separated  points  acts  as  a  conducting  wire  for  the 
current  generated,  and  is  stimulated,  therefore,  at  each  systole. 
Since  the  muscle-nerve  preparation  gives  only  a  simple  contrac- 
tion for  each  ventricular  systole,  we  may  assume  that  this  latter 
contraction  is  itself  simple, — that  is,  due  to  a  single  stimulus. 
The  electrical  variation  may  be  obtained  also  by  means  of  the 
capillary  electrometer  or  the  string-galvanometer  (p.  99),  and 
since  the  movement  of  the  mercury  or  of  the  string  in  these  in- 
struments may  be  photographed,  the  results  can  be  studied  in 
detail.  Owing  to  the  sensitiveness  of  the  instrument,  the  beat 
of  the  human  heart  may  be  registered  in  this  way  (Waller)  when 
the  right  hand,  giving  the  potential  changes  of  the  base  of  the 
heart,  is  connected  with  one  electrode,  and  the  left  hand  (apex 
of  heart)  is  connected  with  the  other.  The  electrocardiograms 
thus  obtained  photographically  show  that,  in  the  ventricle  at 
35 


546  CIRCULATION    OF    BLOOD    AND    LYMPH. 

least,  the  electrical  variation  exhibits  several  phases,  and  the  char- 
acter of  these  phases,  that  is,  whether  the  base  or  the  apex  first 
shows  a  negative  potential,  has  been  used  in  discussions  upon 
the  direction  of  the  wave  of  contraction.  In  Fig.  227  is  given 
an  illustration  of  a  human  electro-cardiogram  obtained  by  con- 
necting the  right  and  left  hands  with  the  electrodes  of  a  string 
galvanometer.  With  such  an  arrangement  or  "lead"  the  elec- 
trode in  the  right  hand  may  be  regarded  as  leading  off  from  the 
auricular  end  of  the  heart,  while  that  in  the  left  hand  leads  off 
from  the  apex  of  the  ventricle.*  As  the  galvanometer  is  arranged, 
a  negativity  (indicative  of  excitation)  toward  the  auricular  end 
is  shown  by  a  movement  above  the  horizontal  base  line,  while 
a  negativity  toward  the  apex  is  shown  by  a  movement  in  the 
opposite  direction.  Similar  electrocardiograms,  differing  in  certain 
details,  may  be  obtained  by  connecting  the  electrodes  with  other 
parts  of  the  body.  In  experimental  as  well  as  clinical  work  it  has 
become  customary  to  use  the  three  "leads"  introduced  by  Ein- 
thoven — namely,  lead  I,  the  electrodes  connected  with  the  right  and 
left  hands  respectively;  lead  II,  right  hand  and  left  foot;  lead  III, 
left  hand  and  left  foot.  The  electrocardiogram  taken  from  lead  I 
(Fig.  227)  shows  three  positive  waves,  P,  R,  and  T,  and  two  nega- 
tive waves,  Q  and  S.  The  first  positive  wave,  P,  indicates  an  initial 
development  of  negativity  toward  the  base  or  auricular  end  of  the 
heart.  All  observers  practically  agree  that  this  wave  is  due  to  the 
contraction  of  the  auricles.  On  the  other  hand,  the  waves  Q,  R,  S, 
and  T  occur  during  the  systole  of  the  ventricles.  R  and  T  are  the 
more  prominent  and  constant  of  these  waves.  Q  and  S  may  be 
absent  or  scarcely  detectable  in  normal  electrocardiograms.  There 
is  much  difference  of  opinion  in  regard  to  the  exact  significance  of 
these  waves.  As  the  galvanometer  is  arranged  and  connected  with 
the  heart  one  can  say  that  the  negative  wave  Q  indicates  the  exist- 
ence of  a  negative  potential  in  the  apical  portion  of  the  heart.  It 
would,  therefore,  suggest  that  the  excitation  wave  reaches  first 
some  region  of  the  heart  toward  the  apex.  The  succeeding  positive 
wave,  R,  indicates,  on  the  contrary,  negativity  and,  therefore,  an 
excitation  toward  the  base  of  the  ventricle.  Following  this  method 
of  interpretation  the  electrocardiogram  has  been  used  to  trace  out 
the  course  of  the  wave  of  excitation  and  contraction  in  the  ventricle, 
but  there  has  been  little  agreement  in  the  conclusions  reached  by 
various  workers.  If  we  can  accept  the  description,  given  in  the 
preceding  paragraph,  of  the  course  of  the  wave  of  excitation  and 
contraction  in  the  ventricle  it  would  seem  that  the  whole  of  the 

*  For  a  description  of  the  Electrocardiogram  and  the  literature  consult, 
James  and  Williams;  "American  Journal  of  the  Medical  Sciences,"  Nov.,  1910, 
or  Kraus  and  Nicolai,  "Das  Elektrokardiogramm,"  Leipzig,  1910. 


THE    HEART    BEAT 


547 


ventricle  should  be  in  a  condition  of  equal  potential  during  systole, 
and  this  appears  indeed  to  be  the  case  in  the  period  between  the  S 
and  T  waves.  But  the  rapid  oscillations  in  potential  at  the  begin- 
ning of  systole  indicated  by  the  Q,  R,  and  S  waves  have  not  been 
explained  satisfactorily  with  reference  to  the  course  of  the  waves  of 
excitation  and  contraction.  The  T  wave  occurs  at  the  end  of  sys- 
tole. According  to  Einthoven  this  wave  may  be  positive  or  nega- 
tive or  be  absent  altogether.  He  interprets  it  to  mean  that  the 
condition  of  contraction  does  not  cease  simultaneously  in  all  parts 
of  the  ventricle.  When,  as  is  usually  the  case,  it  is  positive  it  in- 
dicates a  longer  continuance  of  excitation  and  contraction  in  the 


oiSee. 


Fig.  227.— Electrocardiogram  obtained  by  photographing  the  movements  of  the 
thread  of  a  string-galvanometer.  The  upper  figure  shows  the  photographed  curve,  while 
the  lower  one  is  a  diagram  constructed  from  the  photograph  to  make  clearer  the  electrical 
changes  in  a  single  cardiac  cycle.  To  obtain  this  record  the  electrodes  were  connected 
with  the  right  and  left  hands.  Waves  with  the  apex  upward  indicate  that  the  base  of  the 
heart  (or  the  right  ventricle)  is  negative  to  the  apex  (or  left  ventricle).  Waves  with  the 
apex  downward  have  the  opposite  significance.  Wave  P  is  due  to  the  contraction  of  the 
auricle.  Waves  Q,  R,  S,  and  T  occur  during  the  systole  of  the  ventricle.  (Einthoven). 

basal  portion  of  the  ventricle.*  While  the  precise  significance  of 
the  ventricular  waves  of  the  electrocardiogram  is  not  yet  de- 
termined, it  has  been  found  by  observation  that  variations  in  the 
character  or  sign  of  these  waves  under  pathological  conditions  can 
be  used  in  diagnosis,  particularly  in  the  diagnosis  of  disturbances  of 
the  normal  rhythm.  For  details  in  regard  to  this  point,  reference 
must  be  made  to  clinical  works,  f 

Change  in  Form  of  the  Ventricle  During  Systole. — Much 
attention  has  been  paid  to  the  external  change  of  form  of  the 

*  For  discussion  and  literature  see  Kahn,  "Ergebnisse  d.  PhysioL,"  14, 
1914;  Eyster  and  Meek,  "Archives  of  Int.  Medicine,"  11,  204,  1913,  and  Fahr 
and  Weber,  "Deutsch  Archiv  f.  Klin.  Med.,"  117,  361,  1915. 

t  Barker,  "The  Clinical  Diagnosis  of  Int.  Diseases,"  vol.  i.,  787,  1916. 


548  CIRCULATION    OF    BLOOD    AND    LYMPH. 

ventricle  during  systole.  Does  it  diminish  in  size  in  all  diameters 
or  only  in  certain  diameters?  The  question  is  one  that  cannot 
be  answered  definitely  for  all  normal  conditions,  owing  to  the 
fact  that  the  form  of  the  heart  during  diastole  varies  with  the 
posture  of  the  body.  During  diastole  the  heart  muscle  is 
quite  soft  and  relaxed,  and  consequently  its  shape  is  influenced 
by  gravity.  The  exact  change  of  form  that  it  undergoes  in 
passing  from  diastole  to  systole  will  vary  with  its  shape,  what- 
ever that  may  happen  to  be,  in  diastole.  During  systole  the 
musculature,  on  the  contrary,  is  hard  and  resisting  and  the  form 
of  the  heart  in  this  phase  is  probably  constant.  The  change 
from  the  variable  diastolic  to  the  constant  systolic  form  will  natu- 
rally be  different  in  different  positions.  With  an  excised  frog's 
heart  one  can  show  that  the  ventricle  is  elongated  in  passing  from 
diastole  to  systole  or  one  can  show  the  reverse.  If  the  heart  is  laid 
upon  its  side  it  flattens  in  diastole  so  as  to  increase  in  length, 
and  systole  causes  a  shortening.  If  the  heart  is  held  or  placed 
with  its  apex  pointing  upward  it  flattens  during  diastole  so  as 
to  shorten  the  diameter  from  base  to  apex  and  during  systole 
this  diameter  is  lengthened.  In  ourselves  the  exact  change  of 
shape  is  probably  different  in  the  erect  from  what  it  is  in  the 
recumbent  posture.  Speaking  generally,  the  accounts  agree  in 
stating  that  the  long  diameter  of  the  heart  is  decreased,  base  and 
apex  are  brought  closer  together,  and  the  diameter  from  right  to 
left  is  also  decreased,  while  the  anteroposterior  or  ventrodorsal 
diameter  is  increased.  That  is,  the  outline  of  the  base  of  the  heart 
during  diastole  is  an  ellipse  with  its  short  diameter  in  the  ventro- 
dorsal direction.  During  systole  this  outline  approaches  that  of  a 
circle.  A  more  interesting  change  is  described  for  the  apex  of 
the  ventricle.  Owing  to  the  whorl  made  by  the  superficial  fibers 
at  this  point  as  they  turn  to  pass  into  the  interior  (see  Fig.  223), 
fche  systole  causes  a  rotation  of  the  apex,  which  is  thereby 
forced  more  firmly  against  the  chest  wall.  This  rotation  and 
erection  of  the  apex  during  systole  may  be  seen  upon  the  exposed 
heart  of  the  lower  mammals  and  has  been  described  also  for  man 
in  cases  in  which  the  heart  is  covered  only  by  the  skin,  owing  to 
malformation  in  the  chest  wall  (ectopia  cordis)  or  to  surgical 
operations.  The  exact  position  and  size  of  the  heart  in  man  and 
its  variations  in  these  respects  under  various  normal  and  patho- 
logical conditions  may  be  studied  quite  successfully  by  means  of 
the  z-rays.  When  the  arrays  are  passed  through  the  chest,  the 
heart  forms  a  shadow  which  may  be  seen  with  the  aid  of  the  fluor- 
escent screen  and  which  may  also  be  photographed,  The  appa- 
ratus used  for  this  purpose  may  be  so  arranged  that  the  rays  pass 
through  the  chest  in  parallel  lines  and  give  a  shadow  of  the  exact 


THE    HEART    BEAT. 


549 


size  of  the  heart.  The  arrangement  of  apparatus  for  this  purpose 
is  designated  usually  as  an  orthodiagraph,  and  the  photographic 
record  obtained  is  spoken  of  as  an  orthodiagram.  It  may  be  shown 
by  this  means,  for  example,  that  during  muscular  exercise  there  is 
an  increase  in  the  size  of  the  heart  owing  to  the  greater  venous 
inflow,  while  at  the  end  of  exercise,  with  the  cessation  of  respira- 
tory and  muscular  activity,  the  heart  becomes  smaller  than  normal, 
owing  to  the  fact  that  the  faster  rate,  which  is  maintained  for  a 
while,  causes  the  heart  to  empty  itself  more  rapidly  than  it  is  filled.* 
The  Apex  Beat. — The  apex  of  the  heart  rests  against  the  chest 
wall  at  the  fourth  or  fifth  intercostal  space,  and  here  the  systole 
may  be  seen  and  felt  in  consequence  of  a  slight  protrusion  of  the 
wall.  Much  discussion  has  ensued  as  to  why  this  protrusion 
occurs  during  systole,  since  the  apex  is  drawn  toward  the  base 
and  the  volume  of  the  heart  is  diminished  by  the  output  of 


Fig.  228. — Marey's  cardiograph.  The  button  on  the  tambour  is  pressed  upon  the 
chest  over  the  apex.  The  movements  are  transmitted  through  the  tube  to  the  right  to  a 
recording  tambour. 

blood.  The  fact  seems  to  be  explained  satisfactorily  by  two  con- 
siderations: The  heart  during  diastole  rests  against  the  chest  wall 
at  its  apex  and  a  portion  of  its  anterior  surface,  but  causes  no  pro- 
trusion of  the  wall  because  the  tenseness  of  this  latter  is  sufficient 
to  flatten  or  deform  the  softer  heart  muscle.  During  systole  the 
hardened  heart  muscle,  on  the  contrary,  overcomes  the  now  rela- 
tively less  resistant  integument.  The  rotation  of  the  apex  tends 
also  to  maintain  the  contact;  so  that,  although  the  heart  is  short- 
ened in  its  long  diameter,  the  extent  of  the  movement  is  not 
sufficient  to  draw  it  away  from  the  chest  wall.  In  the  second  place, 
the  discharge  of  the  heart  contents  into  the  curved  aorta  by  tending 
to  straighten  this  tube  causes  a  movement  of  the  whole  heart 
downward  which  counteracts  the  effect  of  the  shortening  in  the 

*  Nicolai  and  Zuntz,  "Berliner  klin.  Wochenschrift,"  No.  18,  1914. 


550  CIRCULATION   OF    BLOOD    AND    LYMPH. 

long  diameter.  The  apex  beat  is  proof  that  the  apex  remains 
against  the  chest  wall  during  systole  and  in  mammals  corroborative 
experiments  have  been  made  by  running  needles  through  the  chest 
wall  into  the  base  and  the  apex  of  the  heart.  Such  needles  act  as 
levers  with  a  fulcrum  in  the  skin,  and  from  the  movement  of  the 
projecting  portion  it  has  been  shown  that,  while  the  basal  portion 
of  the  heart  moves  downward  during  systole,  the  apex  remains 
more  or  less  stationary  except  for  the  lateral  movements  due  to 
the  rotation. 

The  Cardiogram. — The  apex  MCCA,O  may  be  recorded  easily  by 
means  of  appropriate  tambours.  Several  instruments  have  been 
especially  devised  for  this  purpose  and  are  designated  as  cardio- 
graphs. The  cardiograph  described  by  Marey  is  shown  in  Fig.  228. 
It  consists  essentially  of  a  tambour  inclosed  in  a  metal  box.  The 


229.  —  Two  cardiograms  from  the  same  individual  to  show  characteristic  records:   a. 
Beginning  of  systole  ;  b-c,  systolic  plateau.  —  (After  Marey.) 


rubber  membrane  of  the  tambour  carries  a  button  which  can  be 
brought  to  bear,  under  a  suitable  pressure,  upon  the  apex  of  the 
heart.  The  movements  of  this  button  cause  pressure  changes  in 
the  air  of  the  tambour  which  are  transmitted  through  tubing  to  a 
recording  tambour  and  recorded  on  a  kymographion.  A  simple 
and  effective  cardiograph  may  be  made  by  pressing  a  funnel 
against  the  skin  over  the  apex  and  connecting  the  stem  of  the 
funnel  by  tubing  to  a  suitable  recording  tambour.  The  car- 
diograms obtained  by  such  methods  have  been  the  subject  of 
much  discussion.  The  form  of  the  curve  varies  somewhat  with 
the  instrument  used,  the  way  in  which  it  is  applied,  the  position  of 
the  heart  apex  with  reference  to  the  chest  wall,  and  with  the  con- 
ditions of  the  circulation,  and  it  is  often  difficult  to  give  it  a  correct 
interpretation.  An  uncomplicated  form  of  the  cardiogram  is 
represented  in  Fig.  229,  7,  and  a  curve  more  difficult  to  interpret  in 
Fig.  229,  8.  Owing  to  the  number  of  factors  that  alter  the  char- 
acter of  these  curves  they  have  not  proved  to  be  very  useful  in  the 
accurate  study  of  the  character  and  time  relations  of  the  heart  beat. 


THE    HEART    BEAT.  551 

The  Intraventricular  Pressure  During  Systole. — The  best 
analyses  of  the  details  of  the  systole  of  the  ventricle  have  been  made 
by  a  study  of  the  changes  in  pressure  within  the  ventricle.  For 
this  purpose  a  tube  filled  with  liquid  is  introduced  into  the  cavity  of 
the  ventricle.  A  tube  used  for  such  a  purpose  is  designated  as  a 
heart-sound.  For  the  right  ventricle  it  is  introduced  through  an 
opening  in  the  jugular  vein  and  pushed  down  until  it  lies  in  the 


Fig.  230. — Synchronous  record  of  the  intraventricular  pressure  (V),  and  the  aortic 
pressure  (A) :  S,  The  time  record, — each  vibration  =  T^J  sec. ;  0-5,  corresponding  ordi- 
nates  in  the  two  curves;  1  marks  the  opening  ot  the  semilunar  valves;  3  (or  shortly  after) 
marks  the  closure  of  these  valves  and  the  beginning  of  diastole. — (Hiirthle.) 

ventricle,  or  in  some  cases  it  may  be  thrust  through  the  wall  of 
the  ventricle.  For  the  left  ventricle  it  is  introduced  by  way  of  the 
carotid  or  subclavian  artery,  or  through  the  left  auricle  or  ventricle. 
The  sound  is  then  connected  to  a  suitable  recording  apparatus  by 
rigid  tubing  filled  with  liquid.  The  changes  in  pressure  in  the 
ventricle  are  extensive  and  very  rapid.  To  register  them  accu- 
rately the  recording  instrument  must  respond  with  great  prompt- 
ness and  at  the  same  time  must  be  free  from  inertia  movements. 
A  mercury  manometer,  for  instance,  would  be  entirely  useless, 
since  the  heavy  mass  of  mercury  could  not  follow  accurately  the 
quick  changes  in  pressure.  The  recording  manometer  devised 
by  Hiirthle*  has  been  used  for  this  purpose,  as  also  the  optically 
recorded  movements  of  the  more  accurate  segment-capsule  of 
Frank  (p.  498) .  A  typical  curve  obtained  by  means  of  the  Hiirthle 
manometer  is  given  in  Fig.  230,  F,  and  two  curves  as  obtained 
from  an  optical  manometer  (Wiggers)  in  Fig.  230a.  (Consult 
also  the  classical  curve  obtained  by  Chauveau  and  Marey  from  the 
heart  of  the  horse  [Fig.  220].)  It  will  be  seen  that  the  pressure  in 
the  heart  rises  suddenly  with  the  beginning  of  the  ventricular  con- 
traction, and  a  certain  time  elapses  before  this  pressure  is  great 
enough  to  open  the  semilunar  valves.  The  moment  that  this  occurs 
(1,  on  the  ventricular  curve  in  Fig.  230)  is  determined  by  simul- 
*  Hiirthle,  "Archiv  f.  d.  gesammte  Physiologie,"  49,  84,  1891. 


552  CIRCULATION    OF    BLOOD   AND    LYMPH. 

taneous  measurement  of  the  pressure  in  the  aorta,  it  being  evident 
that  the  pressure  will  begin  to  rise  in  this  latter  vessel  the  moment 
that  the  valves  open.  The  different  features  of  the  ventricular 
systole  as  gathered  from  these  pressure  curves  are  as  follows: 
The  systole  of  the  ventricle  exhibits  three  phases  or  periods:  1.  The 
period  of  tension  or  the  isometric  period,  lasting  from  the  begin- 
ning of  the  contraction  to  the  time  of  opening  of  the  semilunar 
valves  (2  to  3  in  Fig.  230a).  During  this  period  the  blood  is  held 


t\ 


\  -3  f      .1 

L5  V        I 


1 


n   \    i    \        A 


*/ V/^Z 


Fig.  230o. — Simultaneous  curves  of  intra ventricular  pressure  and  subclavian  pressure:  X 
and  X'  show  relative  positions.  The  time  curve  indicates  one-fifth  sec.;  2-3,  the  isometric 
period;  3,  opening  of  semilunar  valves;  3-5,  the  ejection  period;  5,  beginning  of  ventricular 
diastole;  b-e,  the  ejection  period  as  it  affects  the  subclavian  pressure;  /,  closure  of  the  semi- 
lunar  valves ;  e-f,  the  incisura,  the  fall  of  pressure  at  the  beginning  of  diastole  which  occasions 
the  closure  of  the  semilunar  valves.— (From  Wiggers.) 

in  the  ventricle,  since  both  the  auriculo-ventricular  and  the  semi- 
lunar  valves  are  closed,  but  it  is  squeezed  upon  by  the  contracting 
muscle  and  the  pressure  rises  very  rapidly.  When  it  exceeds  the 
pressure  in  the  aorta  the  semilunar  valves  are  thrown  open,  blood 
begins  to  flow  from  the  ventricle,  and  the  cavity  of  the  ventricle 
diminishes  in  size.  The  opening  of  the  semilunar  valves  occurs  at 
(3),  and  at  this  point  begins  the  second  period,  the  period  of  empty- 
ing. After  the  semilunar  valves  are  open  pressure  in  the  ventricle 
continues  to  rise  (3  to  4)  owing  to  the  fact  that  the  ventricle  is  dis- 
charging blood  into  the  aorta  more  rapidly  than  it  can  escape  from 
the  aorta  into  the  peripheral  vessels.  When  this  relation  is  reversed 


THE    HEART    BEAT. 


553 


the  pressure  in  the  ventricle  falls.  The  period  of  emptying  closes 
when  the  ventricles  cease  contracting  and  relaxation  begins.  The 
third  period,  the  period  of  relaxation  or  the  period  of  diastole,  be- 
gins with  the  closure  of  the  semilunar  valves  (5).  From  this 
point  the  pressure  within  the  ventricle  falls  very  rapidly.  The 
time  relations  of  the  pressure  changes  in  the  left  ventricle  and  the 
aorta  are  indicated  in  Fig.  230a  (Wiggers).* 

The  Volume  Curve  and  the  Ventricular  Output. — In  man  the 
volume  of  the  heart  under  different  conditions  may  be  studied  by 
means  of  the  x-ray  (p.  548).  In  the  lower  animals  the  thorax 
may  be  opened  with  suitable  precautions  as  regards  anesthesia 
and  artificial  respiration,  and  the  heart  may  be  placed  within  a 
plethysmograph  (see  p.  608)  to  measure  its  changes  in  volume 
during  systole  and  diastole.  If  the  whole  heart  is  treated  in  this 
way  the  curve  of  volume  changes  is  complicated  by  the  fact  that 


—•;«*+• •^••-•a 

Fig.  231. — Diagram  to  show  the  arrangement  of  the  Henderson  cardiometer.  The 
recording  tambour  is  inverted,  so  that  the  systole  will  give  an  up-stroke  on  the  curve. 
(After  Hirschf elder.) 

one  chamber,  the  auricle,  is  filling,  while  the  other,  the  ventricle, 
is  emptying.  A  more  useful  disposition  of  the  apparatus  is  to 
enclose  only  the  ventricles.  Several  different  forms  of  plethysmo- 
graph have  been  devised  for  this  purpose,  and  they  are  usually 
spoken  of  as  cardiometer 's.  The  form  described  by  Henderson  f 
is  simple  and  easily  applied  to  the  heart.  Its  structure  and  the  con- 
nections of  the  recording  apparatus  are  indicated  in  the  diagram 
given  in  Fig.  231.  The  apparatus  consists  of  a  rubber  ball  or  glass 
chamber  with  a  circular  opening  at  one  point.  Over  this  opening  is 
placed  a  membrane  of  rubber  dam  with  a  central  opening  through 
which  the  heart  is  introduced,  as  shown  in  the  diagram.  The  rubber 

*  For  discussion,  see  Tigerstedt,  "Skandinavisches  Archiv  f.  Physiol.," 
28,  37,  1912;  also  Wiggers,  "American  Journal  of  Physiology,"  33,  382,  1914, 
and  "Circulation  in  Health  and  Disease,"  1915. 

t  Henderson,  "American  Journal  of  Physiology,"  16,  325,  1906,  and  23, 
345,  1909.  contain  also  the  literature. 


554 


CIRCULATION    OF    BLOOD    AND    LYMPH. 


membrane  lies  snugly  in  the  auriculoventricular  groove,  making 
an  air-tight  joint.  The  interior  of  the  ball  is  connected  by 
stiff  tubing  with  a  recording  tambour.  By  an  arrangement 
of  this  kind  the  ventricles  are  kept  within  an  air-chamber  closed 
everywhere  except  at  the  outlet  to  the  recording  tambour. 
Every  change  in  volume  of  the  ventricles  will  be  recorded  accu- 
rately provided  there  is  no  leak.  Moreover,  these  volume  changes 
may  be  given  absolute  values  in  cubic  centimeters  if  the  appa- 
ratus is  calibrated  beforehand.  The  cardiometer  furnishes  a 
convenient  method  of  estimating  directly  the  amount  of  blood 
entering  and  leaving  the  ventricles  under  varying  conditions, 
as  well  as  the  changes  in  heart-volume  that  may  result  from 
variations  in  tonicity.  When  the  heart  is  beating  slowly  the 


Fig.  232. — Diagram  of  the  normal  volume  curve  (plethysmogram)  of  the  dog's  heart 
when  beating  at  a  slow  rate  (after  Hirschf elder) .  The  up-stroke  represents  the  systole, 
the  down-stroke  the  diastole;  4  to  5  the  period  of  diastasis  (Henderson).  At  5  the  auricular 
contraction  causes  a  slight  additional  dilatation  of  the  ventricle.  1,  2,  and  3  represent  the 
time  of  occurrence  of  the  first,  second,  and  third  heart-sounds  respectively. 

volume  curve  has  the  form  shown  in  Fig.  232.  During  systole 
the  ventricles  shrink  in  size  as  the  blood  is  discharged  into  the 
aorta  and  pulmonary  artery — the  up-stroke  of  the  curve.  At 
the  end  of  the  systole,  after  the  closure  of  the  semilunar  and  the 
opening  of  the  auriculoventricular  valves,  the  ventricles  are 
dilated  rapidly  by  the  inflow  of  venous  blood.  Henderson  has 
emphasized  the  fact  that  the  filling  takes  place  nearly  as  rapidly 
as  the  emptying,  owing  doubtless  to  the  fact  that  at  the  end  of 
ventricular  systole  the  auricles  are  dilated  under  some  pressure, 
so  that  their  contents  escape  at  once  into  the  ventricles  as  soon 
as  the  intervening  valves  are  opened.  The  diastolic  curve  comes 
back  nearly  to  the  base  line  and  then  forms  a  shoulder  (4)  from 
which  it  approaches  gradually  to  the  base  line  up  to  the  moment  of 
auricular  contraction  (5).  The  period  of  gradual  dilation  of  the 
nearly  filled  ventricles,  which  on  the  curve  is  shown  from  4  to  5,  is 
called  the  period  of  diastasis  by  Henderson.  The  heart  cycle,  so  far 


THE    HEART    BEAT.  555 

as  the  ventricles  are  concerned,  falls,  therefore,  into  three  periods: 
1,  Systole;  2,  diastole;  3,  diastasis.  Variations  in  heart  rate  affect 
chiefly  the  last  period;  this  becomes  shorter  and  shorter  the  more 
rapid  the  rate.  When  the  heart  rate  is  so  rapid  that  the  period 
of  diastasis  drops  out  altogether  and  the  systole  begins  as  soon 
as  the  diastole  is  complete,  then  we  should  have  the  maximum 
output  of  blood  per  minute.  An  increase  of  rate  beyond  this 
point  would  lead  to  a  curtailment  of  the  period  of  diastole  and 
eventually  to  a  diminished  output  of  blood  per  minute.  Accord- 
ing to  the  account  just  given,  the  filling  of  the  ventricle  is 
practically  completed  before  the  auricles  contract.  Henderson 
believes  that  the  contraction  of  the  auricles  adds  very  little  or 
nothing  to  the  change  of  blood  in  the  ventricles,  but  other  authors, 
using  the  same  methods,  differ  from  him  in  this  conclusion. 
It  is  at  least  certain  that  the  ventricles  are  for  the  most  part 
filled  before  the  auricular  contraction  comes  on — this  latter 
act  may  add  a  greater  or  less  amount  to  this  charge,  according 
to  the  extent  to  which  the  inflow  of  venous  blood  during  diastole 
has  filled  the  ventricle.  The  auricular  contraction,  besides  initiat- 
ing the  ventricular  systole,  doubtless  serves,  by  raising  the  tension 
in  the  ventricular  chamber,  to  bring  the  auriculoventricular  valves 
more  completely  into  the  position  of  closure.  When  these  valves 
are  deficient,  as  in  mitral  stenosis,  the  contraction  of  the  auricles 
plays  a  larger  part  in  completing  the  filling  of  the  ventricles 
(Hirschf elder) .  For  the  cases  in  which  it  can  be  applied,  the 
volume  curve  enables  us  to  estimate  the  ventricular  discharge  at 
each  beat  and  the  outflow  per  minute.  It  was  formerly  assumed 
that  at  each  systole  the  ventricles  emptied  themselves  completely, 
but  work  of  the  kind  described  in  this  paragraph  has  shown,  on  the 
contrary,  that  at  the  end  of  systole  a  considerable  proportion  of 
the  blood  may  be  left  in  the  cavity  of  the  ventricle.  The  amount 
thus  left  behind  will  vary  with  the  rate  and  other  conditions. 
According  to  Henderson's  figures  for  the  dog,  about  one-third  or 
somewhat  less  of  the  ventricular  charge  is  left  in  the  heart  after 
systole,  when  the  heart  is  beating  at  the  normal  rate  (90),  and 
the  quantity  of  blood  discharged  from  the  left  ventricle  at  each 
systole  is  approximately  .002  of  the  body  weight.  It  is  evident 
that  when  the  aortic  pressure  rises  to  an  abnormal  level  the 
discharge  of  blood  from  the  left  ventricle  will  be  or  may  be 
diminished,  with  the  result  that  the  blood  backs  up  in  the  left 
auricle,  thus  raising  the  venous  pressure  in  the  lungs  and  retard- 
ing the  pulmonary  circulation.  On  the  other  hand,  as  Hender- 
son has  especially  emphasized,  the  outflow  from  the  ventricle 
must  be  influenced  very  directly  by  the  inflow  into  the  auricle 


556  CIRCULATION    OF    BLOOD    AND    LYMPH. 

from  the  veins.  Variations  in  the  size  of  the  blood-vessels,  such 
as  dilatation  of  the  small  arteries  or  possibly  loss  of  tone  in  the 
veins,  may  bring  about  a  condition  of  venous  stasis  and  cut  down 
the  supply  of  blood  to  the  heart  on  the  venous  side.  Two  ob- 
servers* who  have  studied  by  indirect  means  the  output  of  blood 
from  the  right  ventricle  in  man  state  that  the  volume  of  blood 
discharged  may  vary  from  2.8  liters  per  minute  during  rest  to  as 
much  as  21.6  liters  during  muscular  work.  They  conclude  that 
this  great  range  of  output  is  governed  by  variations  in  the  venous 
filling  of  the  heart  during  diastole.  At  rest  the  venous  inflow  is 
insufficient  to  distend  the  heart  completely,  but  during  muscular 
work  the  increase  in  venous  pressure  and  velocity  distends  the 
heart,  during  diastole,  to  its  maximal  extent. 

The  Heart  Sounds. — An  interesting  and  important  feature 
of  the  heart  beat  is  the  occurrence  of  the  heart  sounds.  Two 
sounds  are  usually  described,  one  at  the  beginning,  the  other 
at  the  end,  of  the  ventricular  systole.  The  first  sound  has 
a  deeper  pitch  and  is  longer  than  the  second,  and  their  relative 
pitch  and  duration  are  represented  frequently  by  the  syllables 
lubb-dup.  According  to  Haycraft,f  both  tones,  from  a  musical 
standpoint,  fall  in  the  bass  clef,  and  are  separated  by  a  musi- 
cal interval  of  a  minor  third.  The  sounds  are  readily 
heard  by  applying  the  ear  to  the  thorax  over  the  heart,  but  for 
diagnostic  purposes  the  stethoscope  is  usually  employed,  and 
this  method  of  investigation  by  hearing  is  designated  as  auscultation. 
The  importance  of  these  heart  sounds  in  diagnosis  was  first  em- 
phasized by  Laennec  (1819),  and  since  his  time  a  great  number  of 
theories  have  been  proposed  to  explain  their  causation.  Indeed, 
the  subject  is  not  yet  closed,  although  certain  general  views  regard- 
ing their  cause  and  the  time  of  their  occurrence  are  generally 
accepted.  The  second  sound  is  found  to  follow  immediately  upon 
the  closure  of  the  semilunar  valves.  The  usual  view,  therefore,  is 
that  the  sound  is  due  ultimately  to  the  vibrations  set  up  in  these 
valves  by  their  sudden  closure.  These  vibrations  are  transmitted 
to  the  column  of  blood  in  the  aorta  (or  pulmonary  artery)  and  then 
to  the  intervening  tissue  of  the  chest  wall.  This  view  is  made 
probable  by  a  number  of  experimental  results,  some  of  the  most 
important  of  which  were  brought  out  by  Williams  in  a  report  (1836) 
of  a  committee  appointed  by  the  British  Association  for  the 
special  purpose  of  investigating  the  subject.  It  has  been  shown: 
(1)  That  the  second  sound  disappears  before  the  first  sound  when 

*  Krogh  and  Lindhard,  "Skandinavisches  Archiv  f.  Physiologic,"  27,  100, 
1912. 

t  "Journal  of  Physiology,"  11,  486,  1890. 


THE    HEART    BEAT.  557 

the  animal  is  bled  to  death,  and  indeed  as  soon  as  the  heart  ceases 
to  throw  out  a  supply  of  blood  sufficient  to  maintain  aortic  tension. 
It  disappears  also  when  cuts  are  made  in  the  ventricles  so  that  the 
blood  may  escape  otherwise  than  through  the  arteries.  (2)  When 
the  valves  of  the  pulmonary  artery  and  aorta  are  hooked  back  in  the 
n'ving  animal  the  second  sound  is  replaced  by  a  murmur  due  to  the 
rushing  back  of  the  blood  into  the  ventricle,  and  if  the  valves  are 
dropped  back  into  place  the  normal  second  sound  is  again  heard. 
(3)  Similar  sounds  may  be  produced  if  the  root  of  the  aorta  with  its 
valves  in  place  is  excised  and  attached  to  a  glass  tube  carrying  a 
column  of  water.  With  such  an  arrangement,  if  the  valves  are  held 
open  for  a  moment  and  then  closed  sharply  by  the  pressure  of  the 
column  of  water  a  sound  similar  to  that  of  the  second  heart  sound 
is  heard. 

The  physician  uses  this  view  of  the  cause  of  the  second  sound  in 
auscultation,  and  it  is  evident  that  the  nature  of  the  sound  or  its 
replacement  by  murmurs  will  give  useful  testimony  regarding  the 
condition  of  the  semilunar  valves.  The  first  heart  sound  has  of- 
fered more  difficulty.  It  occurs  at  or  shortly  before  the  closure  of  the 
auriculo-ventricular  valves,  and  it  would  seem  natural,  therefore,  to 
attribute  it  to  the  vibration  of  these  valves  when  suddenly  put  under 
tension  by  the  ventricular  systole.  Most  authors,  indeed,  believe 
that  this  factor  is  at  least  partially  responsible  for  the  sound, — 
that  is,  that  the  sound  contains  a  valvular  element.  But  that  this 
is  not  the  sole  cause  is  shown  by  the  fact  that  the  bloodless  beating 
heart  still  gives  a  sound  at  the  time  of  the  ventricular  systole. 
Indeed,  if  the  apex  of  the  rabbit's  heart  is  cut  off,  it  continues 
to  beat  for  a  few  minutes  and  during  this  time  gives  a  first  heart 
sound.  It  is  usually  said,  therefore,  that  the  first  heart  sound  is 
caused  by  the  combination  of  at  least  two  factors, — a  valvular 
element  due  to  the  vibration  of  the  auriculo-ventricular  valves,  and 
a  muscular  element  due  to  the  vibration  of  the  contracting  muscular 
mass.  Accepting  this  view,  there  is  a  further  difficulty  in  explain- 
ing the  origin  of  the  muscular  element.  According  to  some,  it  is 
due -to  the  fact  that  the  contraction  of  the  muscle  fibers  is  not 
simultaneous  throughout  the  ventricle  and  the  friction  of  the  inter- 
lacing fibers  sets  up  vibration  in  the  muscular  mass;  according  to 
others,  the  so-called  muscular  element  is  mainly  a  resonance  tone  of 
the  ear  membrane  of  the  auscultator, — the  shock  of  the  contracting 
heart  sets  the  tympanic  membrane  to  vibrating.  It  seems  useless 
to  attempt  a  detailed  discussion  of  these  conflicting  views,  since  no 
convincing  statements  can  be  made.  Practically,  the  time  at  which 
the  heart  sounds  occur  is  of  great  importance.  A  number  of 
observers  have  recorded  the  time  upon  a  cardiographic  tracing  of 


558  CIRCULATION    OF    BLOOD    AND    LYMPH. 

the  heart  beat  with  results  such  as  are  shown  in  Fig.  233.  The 
figure  shows  clearly  the  general  fact  that  the  first  sound  is  heard 
very  shortly  after  the  beginning  of  systole  and  the  second  one 
immediately  after  the  end  of  systole.  The  first  sound  is  therefore 
systolic,  and  the  second  sound  diastolic.  A  more  exact  and  de- 
tailed study  of  the  time  relations  of  the  heart  sounds  has  been  made 
by  Einthoven  and  Geluk.*  These  authors  obtained  graphic  records 
of  the  heart  sounds.  The  sounds  received  first  by  a  microphone 
were  transmitted  to  a  capillary  electrometer  and  the  movements 
of  the  latter  were  photographed.  As  one  result  of  their  work  they 
give  the  schema  shown  in  Fig.  234.  It  will  be  seen  from  this  figure 
that  the  first  sound  begins  about  0.01  sec.  before  the  cardiogram 
shows  the  commencement  of  systole,  and  that  for  the  first  0.06  sec. 


Fig.  233.— -To  show  the  time  relation  of  the  heart  sounds  to  the  ventricular  beat 
(Marey) :  V.D.,  Tracing  of  the  ventricular  pressure  in  the  right  ventricle  of  the  horse.  Be- 
low the  two  marks  show,  respectively,  the  time  of  the  first  and  second  sounds.  The  first 
occurs  immediately  after  the  beginning  of  systole,  the  second  immediately  after  the  begin- 

the  sound  is  heard  only  over  the  apex  of  the  heart  (a-6).  Over  the 
base  of  the  heart  (second  intercostal  space)  the  first  sound  is  heard 
(b  to  c-d)  just  at  the  time  when  the  semilunar  valves  are  opened 
(6'), — that  is,  at  the  beginning  of  the  period  of  emptying  according 
to  the  classification  given  on  p.  552.  The  first  sound  ceases  long 
before  the  ventricular  contraction  itself  is  over, — a  fact  which 
would  seem  to  indicate  that  the  muscular  element  in  the  first  sound 
is  not  a  muscular  sound,  such  as  is  given  out  by  a  contracting 
skeletal  muscle.  The  beginning  of  the  second  sound  seems  to  mark 
exactly  the  time  of  closure  of  the  semilunar  valves.  The  character 
and  the  time  relations  of  the  murmurs  that  accompany  or  replace 
the  heart  sounds  form  the  interesting  practical  continuation  of  this 
theme;  but  the  subject  is  so  large  that  the  student  must  be  referred 
for  this  information  to  the  works  upon  clinical  methods.  ' 

The  Third  Heart  Sound. — Several  observers*  have  called 
attention  to  the  fact  that  in  certain  individuals  a  third  heart 

*  Einthoven  and  Geluk,  "Archiv  f .  d.  gesammte  Physiologic,"  57,  617, 
1894.  Einthoven,  ibid.,  1907,  vol.  117.  Fahr,  "Heart,"  4,  147,  1912, 

fThayer,  "Boston  Med.  and  Surg.  Journal.''  158,  713.  1908;  Einthoven, 
"Archiv  f.  d.  ges.  Physiol.,"  120,  31,  1907;  Gibson,  "Lancet,"  1907,  II,  1380. 


THE    HEART    BEAT.  559 

sound  may  be  heard  very  shortly  (0.13  sec.)  after  the  beginning 
of  the  second  sound.  Thayer  describes  this  sound  as  being 
" softer  and  of  lower  pitch"  than  the  second  sound,  and  in  some 
cases  as  resembling  rather  a  dull  thud  or  hum.  In  those  persons 
in  whom  it  can  be  detected  it  is  heard  most  distinctly  over  the 
apex  of  the  heart.  Einthoven  has  shown  the  existence  of  this 
sound  by  objective  methods.  •  By  means  of  a  microphone 
attachment  the  heart  sounds  can  be  transmitted  to  the  string- 
galvanometer,  in  which  they  cause  deflections  of  the  string  that 
can  be  photographed.  In  this  way  he  has  obtained  records  of 


Fig.  234. — Schematic  representation  of  the  relation  of  the  heart  sounds  to  the  ventric- 
ular beat:  C,  The  cardiogram;  1,  to  show  the  duration  of  the  first  heart  sound;  2,  the 
duration  of  the  second  heart  sound;  S,  the  time  record,  each  division  corresponding  to 
0.02  sec.  In  1,  a-a'  marks  the  instant  that  the  first  heart  sound  is  heard  over  the  apex, 
and  b-b'  the  moment  that  it  is  heard  at  the  second  intercostal  space. — (Einthoven  and 
Geluk.) 

the  third  sound  upon  individuals  in  whom  the  stethoscope  failed 
to  reveal  its  existence.  The  cause  of  this  sound  has  been 
explained  differently  by  the  several  authors  who  have  investi- 
gated it.  It  occurs  early  in  the  diastole,  and  Einthoven  suggests 
that  it  is  due  to  an  after-vibration  of  the  semilunar  valves. 
Thayer  and  Gibson  suggest  the  more  probable  explanation  that 
it  is  due  to  a  vibration  of  the  auriculoventricular  valves  which 
is  set  up  by  the  sudden  inrush  of  blood  from  the  auricles 
at  the  beginning  of  diastole.  This  inflow  of  venous  blood 
distends  the  ventricle  sharply  and  throws  the  valves  into  a 
position  of  closure  with  some  suddenness.  The  sound  occurs 
at  about  the  time  of  the  shoulder  on  the  diastolic  limb  of  the 
volume  curve,  as  is  indicated  in  the  diagram  in  Fig.  232. 

The  Events  that  Occur  During  a  Single  Cardiac  Cycle.— 
By  a  complete  cardiac  cycle  is  meant  the  time  from  any  given 
feature  of  the  heart  beat  until  that  feature  is  again  produced. 
It  may  be  helpful  to  summarize  the  events  in  such  a  cycle,  both 
as  regards  the  heart  and  as  regards  the  blood  contained  in  it. 
We  may  begin  with  the  closure  of  the  semilunar  valves.  At 
that  moment  the  second  heart  sound  is  heard  and  at  that 
moment  the  ventricle  is  quickly  relaxing  from  its  previous 


560  CIRCULATION    OF    BLOOD    AND    LYMPH. 

contraction.  Since  the  auriculo ventricular  valves  are  still 
closed  (see  diagram,  Fig.  219),  the  ventricles  for  a  brief  interval 
are  shut  off  on  both  sides.  The  blood  is  flowing  steadily  into 
the  auricles  and  dilating  them.  As  soon  as  the  ventricles  relax 
the  pressure  of  blood  in  the  auricles  opens  the  auriculoven- 
tricular  valves,  and  from  that  moment  until  the  beginning  of 
the  auricular  systole  the  blood  from  the  large  veins  is  filling 
both  ventricles  and  auricles.  As  stated  on  p.  554,  the  venous 
blood  which  has  been  accumulating  in  the  auricles  during  the 
ventricular  systole  flows  into  the  ventricles  with  some  sudden- 
ness on  the  opening  of  the  auriculoventricular  valves.  The 
ventricles,  therefore,  dilate  rapidly  and  the  auriculoventricular 
valves  are  floated  into  a  position  ready  for  closure.  This  event 
occurs  at  about  the  time  that  the  third  heart  sound  is  heard. 
In  a  slowly  beating  heart  there  may  be  quite  an  interval  (period 
of  diastasis)  between  this  point  and  the  auricular  contraction. 
The  auricular  systole  sends  a  sudden  wave  of  blood  into  the 
ventricles,  dilating  them  still  further  and  momentarily  blocking 
or  retarding  the  flow  from  the  large  veins,  and  causing  one  of 
the  waves  seen  in  the  normal  venous  pulse  as  recorded  in  the 
jugular  veins.  The  ventricular  systole  follows  at  once  upon 
the  auricular  systole,  the  exact  relations  in  this  case  depend- 
ing somewhat  upon  the  pulse  rate.  As  the  ventricle  enters 
into  contraction  the  auriculo-ventricular  valves  are  tightly  closed, 
the  first  sound  is  heard,  and  for  a  short  interval  the  ventricular 
cavity  is  again  shut  off  on  both  sides.  Soon  the  rising  pressure  in 
the  interior  forces  open  the  semilunar  valves,  and  then  a  column 
of  blood  is  discharged  into  the  aorta  and  pulmonary  artery  as  long 
as  the  contraction  lasts.  During  this  interval  the  flow  at  the. 
venous  end  of  the  heart  continues,  the  blood  being  received  into 
the  yielding  auricles.  Indeed,  this  capacity  for  receiving  the 
venous  inflow  during  the  comparatively  long-lasting  ventricular 
systole  may  be  considered  as  one  valuable  mechanical  function 
fulfilled  by  the  auricles.  The  venous  flow  is  never  completely 
blocked  and  at  the  most  suffers  only  a  slight  retardation  during 
the  very  brief  auricular  systole.  At  the  end  of  the  ventricular  sys- 
tole the  excess  of  pressure  in  the  aorta  and  the  pulmonary  artery 
closes  the  semilunar  valves  and  completes  the  cycle. 

Time  Relations  of  Systole  and  Diastole. — The  duration  of  the 
separate  phases  of  the  heart  beat  depends  naturally  on  the  rate 
of  beat.  Assuming  a  low  pulse  rate  of  70  per  minute,  the  average 
duration  of  the  different  phases  may  be  estimated  as  follows: 

Ventricular  systole =  0.379  sec. 

Ventricular  diastole  and  pause =  0.483    " 

Auricular  systole =0.1      to  0.17      " 

Auricular  diastole  and  pause =  0.762  to  0.692    " 


THE    HEART    BEAT.  561 

Einthoven  and  Geluk,  in  the  investigation  referred  to  above, 
measured  the  time  intervals  of  systole  and  diastole  during  fifteen 
heart  periods  of  a  healthy  man,  and  found  that  the  time  for  the 
ventricular  systole  varied  between  0.312  and  0.346  sec.,  while  that 
for  the  diastole  varied  from  0.385  to  0.518  sec.  Experiments  by 
a  number  of  observers  indicate  that  in  the  great  changes  of  rate 
which  the  heart  may  undergo  under  normal  conditions  the  diastolic 
phase  (period  of  diastasis)  is  affected  relatively  much  more  than 
the  systolic,  as  we  should  expect. 

The  Normal  Capacity  of,  the  Ventricles  and  the  Work  Done 
by  the  Heart. — Various  efforts  have  been  made  to  measure 
the  normal  capacity  of  the  ventricles  in  man,  but  the  deter- 
mination has  encountered  many  difficulties.  Experiments  and 
observations  made  upon  the  excised  heart  are  of  little  value,  since 
the  distensible  walls  of  the  ventricles  yield  readily  to  pressure, 
and  it  is  difficult  or  impossible  to  imitate  exactly  the  conditions 
of  pressure  that  prevail  during  life.  Nor  is  it  certain  whether 
normally  the  ventricles  empty  themselves  completely  during 
systole;  in  fact,  the  evidence  from  experiments  on  the  lower 
animals  indicates  that,  contrary  to  the  opinion  which  for- 
merly prevailed,  the  ventricles  throw  out  only  a  portion  of  their 
blood  at  each  beat.  The  older  observers  (Volkmann,  Vierordt) 
attempted  to  arrive  at  a  determination  of  the  normal  output 
of  the  ventricles  by  calculations  based  upon  the  velocity  of 
the  blood  in  the  carotid  and  the  width  of  the  stream  bed.  from 
observations  on  many  animals  they  arrived  at  the  general- 
ization that  at  each  systole  the  amount  of  blood  ejected 
from  the  ventricles  is  equal  to  about  TOT  of  the  body  weight.  For 
a  man  weighing,  say,  72  kilograms  (158  Ibs.)  this  ratio  would  give 
an  output  for  each  systole  of  180  gms.  (6  ozs.).  More  recent 
observers,  however,  have  found  this  estimate  too  high.  Ho  well 
and  Donaldson*  measured  the  output  directly  for  the  heart  of  the 
dog,  making  use  of  a  heart  isolated  from  the  body  and  kept  beating 
by  an  artificial  circulation.  The  ratio  of  the  output  varied  with  the 
rate  of  beat;  for  a  rate  of  180  beats  per  minute  it  was  equal  to 
0.00117  (-5-^-)  of  the  body  weight;  for  a  rate  of  120  beats  per  minute 
it  was  equal  to  0.0014  (-7^5-).  This  ratio  is  therefore  about  one-half 
of  that  proposed  by  Volkmann.  Tigerstedt,  from  observations 
upon  rabbits,  obtained  a  lower  ratio  still  (0.00042);  but  from  his 
own  results  and  those  obtained  by  other  workers  he  concludesf 
that  an  average  valuation  for  the  volume  of  blood  discharged  by 
each  ventricle  of  the  human  heart  is  from  50  to  100  c.c.  On  this 
basis  one  may  make  an  approximate  estimate  of  the  work  done 

*  Howell  and  Donaldson,  "Philosophical  Transactions,"  Royal  Soc.,  Lon- 
don, 1884. 

t  Tigerstedt,  "Lehrbuch  der  Physiologie  des  Kreislaufes,"  p.  152,  1893. 


562  CIRCULATION    OF    BLOOD   AND    LYMPH. 

at  each  beat.  Using  Tigerstedt's  figures,  such  results  as  the  follow- 
ing are  obtained:  On  the  left  side  the  heart  empties  its  100  c.c. 
against  a  pressure  of  15  cm.  Hg.  and  on  the  right  side  against  a 
pressure  of,  say,  6  cm.  Hg.  The  work  done  may  be  calculated  from 
the  general  formula  W  =  FS  —  that  is  to  say,  the  work  W  is  equal  to 
the  product  of  the  force  F  into  S,  the  space  or  distance  through 
which  the  force  acts.  If  the  left  ventricle  empties  100  c.c.  of  blood 
at  each  systole  into  the  aorta,  then,  since  the  diameter  of  the  aorta 
is,  say,  3  cm.,  there  is  forced  out  of  the  ventricle  a  column  of  blood 
about  14  cm.  long  with  a  cross  area  of  7  sq.  cm.  This  column  is 
driven  out  of  the  ventricle  against  a  pressure  or  resistance  equiva- 
lent to  the  weight  of  a  column  of  mercury  15  cm.  high,  or,  counting 
the  specific  gravity  of  blood  as  1.06,  a  column  of  blood  192  cm.  high 

"I  Q  A  \ 

(15  X  ^gl     This  is  equivalent  to  saying  that  at  each  systole  the 

left  ventricle  lifts  a  column  of  blood  192  cm.  long  and  with  a  cross 
area  of  7  sq.  cm.  to  a  height  of  14  cm.  A  column  of  blood  192  cm. 
high  with  a  cross  area  of  7  sq.  cm.  weighs  1425  gm.  (192X7  X  1.06). 
To  move  this  weight  through  a  distance  of  14  cm.  means  the  per- 
formance of  19,950  gm.  cm.  of  work  (1425X14).  In  addition  to 
this  work  which  represents  the  overcoming  of  a  resistance  there  is 
the  further  work  represented  by  the  velocity  communicated  to  the 
blood  discharged  from  the  ventricle.  The  kinetic  energy  of  this 
moving  massfriay  be  calculated  from  the  formula: 


Substituting  for  m  its  value  of  ?,  in  which  p  represents  the  weight 
and  g  the  acceleration  of  gravity  (p  —  mg,  hence  m  =  -),  then 
E  =  ^-  in  which  p  is  equal  to  106  gm.  and  v  to  50  cm.,  the  average 

1  Ofi  V  ^fP 

velocity  of  the  blood  in  the  aorta.  Q81  ^  2  =  13^  &&•  cm-  °^ 
work.  The  total  work  done  by  the  left  ventricle,  therefore,  at  each 
systole  is  equal  to  20,085  gm.  cm.  A  similar  calculation  will  give 
the  work  done  by  the  right  ventricle.  The  calculations  made  by 
different  authors  as  to  the  amount  of  blood  discharged  from  each 
ventricle  during  systole  may  be  tabulated  as  follows: 


Thomas  Young 45  gms. 

Volkmann 

Vierordt 180 

Fick 50-73 

Howell  and  Donaldson 75-90 

Hoorweg 47 

Zuntz 60 

Tigerstedt 50-100 

Plumier 70 

Loewy  and  v.  Schrotter 55 

Krogh  and  Lindhard 39-103 


for  weight  of  72  kgms. 

K  t(  (I       K  t( 


65 


60-65  kgms. 


THE    HEART    BEAT.  563 

The   Coronary   Circulation   during  the   Heart   Beat. — The 

condition  of  the  blood-flow  in  the  coronary  vessels  during  the  phases 
of  the  heart  beat  has  been  the  subject  of  much  speculation  and 
experiment,  since  it  has  entered  as  a  factor  in  the  discussion  of 
several  mechanical  and  nutritive  problems  that  are  connected  with 
the  physiology  of  the  heart.  According  to  a  view  usually  attributed 
to  Thebesius  (1708),  the  flaps  of  the  semilunar  valves  are  thrown 
back  during  systole  and  shut  off  the  coronary  circulation,  and 
therefore  the  coronary  vessels,  unlike  those  of  other  organs,  are 
filled  during  diastole.  In  modern  times  this  view  has  been  revived 
by  Briicke,  who  made  it  a  part  of  his  theory  of  the  "  self-regulation  " 
of  the  heart  beat.  According  to  this  view,  the  coronaries  are  shut 
off  from  the  aorta  during  systole  by  the  flaps  of  the  semilunar  valves, 
so  that  the  contraction  of  the  ventricle  is  not  opposed  by  the 
distended  arteries,  while,  on  the  other  hand,  the  reinjection  of  these 
vessels  from  the  aorta  during  diastole  aids  in  the  dilatation  of  the 
ventricular  cavities.  Experimental  work  has  shown  decisively  that 
the  part  of  this  theory  relating  to  the  closure  of  the  coronary  arteries 
by  the  semilunar  valves  is  incorrect.*  Records  of  pressure  changes 
in  the  coronary  arteries  during  the  heart  beat  made  by  Martin  and 
Sedgwick  and  by  Porter  show  that  they  are  substantially  identical 


Fig.  235. — Simultaneous  record  of  the  blood-pressure  (A)  and  the  blood-velocity  (B) 
ill  the  coronary  arteries  (Chauveau  and  Rebatel):  a,  Marks  the  beginning  of  the  systole 
(there  is  a  rise  in  pressure  and  in  velocity) ;  b,  marks  a  second  rise  of  pressure  (A)  due  to 
the  closure  of  the  coronary  capillaries  by  the  contracting  ventricle  (at  this  moment  in  B 
the  velocity  falls  off  rapidly) ;  c,  curve  (B)  shows  an  increase  in  velocity  due  to  the  open- 
ing of  the  small  coronary  vessels  at  the  beginning  of  diastole. 

with  those  in  the  carotid  or  aorta,  and  records  of  the  velocity  of  the 
blood-flow  made  by  Rebatel  show  that  at  the  beginning  of  systole 
the  flow  in  the  coronaries  suffers  a  sudden  systolic  acceleration  as  in 
the  case  of  other  arteries.  During  systole,  therefore,  the  mouths  of 
the  coronary  arteries  are  in  free  communication  with  the  aorta. 
But  the  coronary  system — arteries,  capillaries,  and  veins — is  in 
part  imbedded  in  the  musculature  of  the  ventricles,  and  we  should 

*See  Porter,  "  American  Journal  of  Physiology,"  1,  145,  1898,  for  dis- 
cussion and  literature. 


564  CIRCULATION    OF   BLOOD    AND    LYMPH. 

suppose  that  the  great  pressure  exerted  by  the  contracting  muscu- 
lature would  at  the  height  of  systole  clamp  off  this  system  and  stop 
the  coronary  circulation.  That  this  result  really  happens  is  indi- 
dicated  by  RebatePs  curves  of  the  velocity  of  the  flow  in  the  coro- 
nary arteries.  As  shown  in  Fig.  235,  the  great  acceleration  (a)  in 
velocity  at  the  beginning  of  systole  is  quickly  followed  by  a  drop  to 
zero  (6)  or  even  a  negative  value, — that  is,  a  flow  in  the  other  direc- 
tion, toward  the  aorta.  At  the  end  of  the  first  (relaxation)  phase 
of  diastole  there  is  again  a  sudden  increase  in  velocity  (c),  corre- 
sponding with  the  injection  of  the  arteries  from  the  aorta,  followed 
again  by  a  decrease  at  the  end  of  the  diastole  at  the  time  when  the 
ventricular  cavity  is  filled  with  venous  blood  under  some  pressure. 
Porter,  moreover,  has  shown  in  an  interesting  series  of  experiments 
that  when  a  piece  of  the  ventricle  is  kept  beating,  by  supplying  it 
with  blood  through  its  nutrient  artery  from  a  reservoir  at  con- 
stant pressure,  each  systole  causes  a  jet  of  blood  from  the  sev- 
ered vessels  at  the  margin  of  the  piece.  In  fact,  the  rhythmical 
squeeze  of  its  own  vessels  during  systole  accelerates  effectively  the 
coronary  circulation.  The  volume  of  blood  flowing  through  the 
heart  vessels  increases  with  the  frequency  or  the  force  of  the  beat, 
since  each  systole  empties  the  coronary  system  more  or  less  com- 
pletely toward  the  venous  side  and  at  each  diastole  the  distended 
aorta  quickly  fills  the  empty  vessels. 

The  Suction-pump  Action  of  the  Heart. — So  far  in  con- 
sidering the  mechanics  of  the  circulation  attention  has  been  directed 
only  to  the  force-pump  action  of  the  heart.  All  of  the  energy  of  the 
circulation,  the  velocity  of  the  flow  and  the  internal  pressure,  has 
been  referred  to  the  force  of  contraction  of  the  ventricles  as  the 
main  cause,  and  to  certain  accessory  factors,  such  as  the  respiratory 
movements  and  the  contractions  of  the  skeletal  muscles,  as  subsid- 
iary causes.  It  is  possible,  however,  that  the  heart  may  also  act  as 
a  suction-pump,  sucking  in  blood  from  the  venous  side  in  conse- 
quence of  an  active  dilatation.  According  to  this  view,  the  heart 
works  after  the  manner  of  a  syringe  bulb,  which  when  squeezed 
forces  out  liquid  from  one  end  and  when  relaxed  sucks  it  in  from 
the  other  in  consequence  of  its  elastic  dilatation.  While  this  view 
has  long  been  entertained,  modern  interest  in  it  was  aroused  chiefly 
perhaps  by  the  experiments  of  Goltz  and  Gaule,  which  showed  that 
at  some  point  in  the  heart  beat  there  is  or  may  be  a  strong  negative 
pressure  in  the  interior  of  the  ventricles.*  Their  method  consisted 
in  connecting  a  manometer  with  the  interior  of  the  ventricle  and 
interposing  between  the  two  a  valve  that  opened  only  toward  the 
heart.  The  manometer  was  thus  converted  into  a  minimum 

*  For  a  complete  discussion  of  this  subject  and  the  literature  see  the  ar- 
ticle by  Ebstein,  "  Die  Diastole  des  Herzens,"  in  the  "  Ergebnisse  der  Physi- 
ologic," vol.  iii,  part  n,  1904. 


THE    HEART    BEAT.  565 

manometer,  which  registered  the  lowest  pressure  reached  during 
the  period  of  observation.  By  this  method  they  and  others  have 
shown  that  in  an  animal  (dog)  with  an  opened  thorax  the  pressure 
in  the  interior  of  the  ventricles  may  be  negative  to  an  extent  equal 
to  20,  30,  or  even  50  mms.  of  mercury.  Moreover,  by  the  use  of 
some  form  of  elastic  manometer,  such  as  the  Hiirthle  instrument 
(p.  498). it  has  been  shown  that  this  negative  pressure  occurs  at  the 
end  of  the  period  of  relaxation,  at  the  time,  therefore,  at  which  it 
might  be  supposed  to  exert  a  marked  influence  upon  the  inflow  of 
venous  blood.  It  should  b6  added,  however,  that  a  negative 
pressure  can  not  be  shown  for  every  heart  beat.  It  may  be  absent 
altogether  or  slight  in  amount,  varying,  no  doubt,  with  the  force  of 
contraction  and  the  condition  of  the  heart.  With  regard  to  the 
extent  of  the  influence  of  this  negative  pressure  on  the  flow  of 
venous  blood  to  the  ventricles  there  has  been  some  difference  of 
opinion.  Direct  experiments  made  by  Martin  and  Donaldson* 
indicate  that  this  factor  has  little  or  no  actual  influence  upon  the 
venous  flow.  These  authors  used  an  isolated  dog's  heart  kept 
beating  by  an  artificial  supply  of  blood.  At  a  given  moment  the 
stream  of  blood  into  the  vena  cava  was  shut  off  and  the  auricle  of 
the  heart  was  brought  into  communication  with  a  U  tube  filled 
with  blood.  It  was  found  that  the  auricle  took  blood  from  this 
tube  only  so  long  as  the  pressure  in  the  tube  was  positive.  Although 
the  heart  continued  to  beat  vigorously,  whatever  negative  pressure 
was  present  in  the  ventricle  was  unable  to  suck  any  blood  into  the 
auricle  from  the  U  tube.  Porter  f  also  has  shown  that  at  the  time 
of  a  strong  negative  pressure  in  the  ventricle  the  auricle  may  give 
little  or  no  evidence  of  a  similar  fall  in  pressure.  It  would  seem 
most  probable,  therefore,  that  the  negative  pressure  observed  under 
certain  conditions  in  the  ventricles  is  a  fleeting  phenomenon,  and 
disappears  with  the  entrance  of  the  first  portion  of  the  blood  from 
the  auricles.  While  it  may  be  of  value  in  accelerating  the  opening 
of  the  auriculo- ventricular  valves,  its  influence  does  not  extend  to  an 
actual  suction  of  the  blood  from  the  veins  toward  the  heart. 
Other  authors,  however,  on  theoretical  grounds  attribute  more 
actual  importance  to  the  negative  pressure  as  a  factor  in  moving 
the  blood. 

Occlusion  of  the  Coronary  Vessels. — The  coronary  vessels'sup- 
ply  the  tissues  of  the  heart  with  nutrition,  including  oxygen,  so 
that  if  the  circulation  is  interrupted  the  normal  contractions  soon 
cease.  The  branches  of  the  large  coronaries  form  what  are  known 

*  Martin  and  Donaldson,  "Studies  from  the  Biological  Laboratory,  Johns 
Hopkins  University,"  4,  37,  1887;  also  Martin's  "Physiological  Papers," 
Baltimore,  1895.  See  also,  for  confirmatory  results,  von  den  Velden,  "Zeit- 
schrift  f.  exp.  Pathol.  u.  Therapie,"  1906,  iii.,  432. 

t" Journal  of  Physiology,"  13,  513,  1892. 


566  CIRCULATION    OF    BLOOD    AND    LYMPH. 

as  terminal  arteries, — that  is,  each  supplies  a  separate  region  of  the 
musculature,  and  although  anastomoses  may  exist  they  appear 
to  be  too  incomplete  to  allow  a  collateral  circulation  to  be  estab- 
lished when  one  of  the  main  arteries  is  occluded.  The  portion  of 
the  heart  supplied  by  it  dies,  or  to  use  the  pathological  term,  under- 
goes necrosis.  On  account  of  the  pathological  interests  involved — 
the  known  serious  results  that  may  follow  occlusion  of  any  of  the 
coronary  vessels  or  even  any  interference  with  the  normal  structure 
of  the  vessels — a  number  of  investigations  have  been  made  upon  ani- 
mals to  determine  the  effect  of  occluding  one  or  more  of  the  coronary 
vessels.*  It  would  seem  from  Porter's  experiments  that  the  results 
of  such  an  operation  vary  according  to  the  size  of  the  area  deprived 
of  its  blood.  When  the  arteria  septi  alone  was  occluded  the  heart 
was  not  affected,  when  the  arteria  coronaria  dextra  was  occluded 
the  ventricular  contractions  were  arrested  in  18  per  cent,  of  the 
cases  observed.  Occlusion  of  the  ramus  descendens  of  the  left 
coronary  artery  caused  arrest  of  the  ventricles  in  50  per  cent,  of  the 
cases,  while  occlusion  of  the  circumflex  branch  of  the  same  artery 
caused  arrest  in  80  per  .cent,  of  the  cases.  Ligation  of  three  of  the 
arteries  caused  stoppage  of  the  heart  in  all  cases. 

Fibrillary  Contractions. — The  arrest  of  the  ventricles  in  the 
experiments  just  described  followed  immediately  or  within  a  short 
period,  and  the  ventricles  went  into  fibrillary  contractions.  In  this 
curious  condition  the  various  fibers  of  the  ventricular  muscle,  in- 
stead of  contracting  together  in  a  co-ordinated  fashion,  contract 
separately  and  irregularly;  so  that  the  surface  of  the  ventricle  has 
the  appearance  of  a  vibrating,  twitching  mass.  Such  a  condition 
in  the  ventricle  is  usually  fatal — that  is,  the  musculature  is  not  able 
to  recover  its  co-ordinated  movement.  This  condition  may  come 
on  with  great  suddenness  as  the  result  of  occlusion  of  the  arteries, 
of  injury  to  certain  parts  of  the  heart,  or  from  strong  electrical 
stimulation.  Fibrillation  of  the  auricles  also  occurs  frequently 
under  experimental  conditions,  and,  indeed,  in  the  human  heart  ap- 
parently under  pathological  conditions.  When  the  auricles  are 
thrown  into  fibrillation  by  experimental  means  the  ventricles  con- 
tinue to  beat,  but  in  an  irregular  manner  similar  to  a  condition 
sometimes  observed  in  man  and  described  usually  under  the  term 
pulsus  irregularis  perpetuus.  There  is  reason  to  believe  that  this 
condition  in  man  is  attributable  to  a  fibrillation  of  the  auricles*  f 
The  cause  of  the  sudden  change  from  co-ordinated  to  fibrillary  con- 
tractions has  never  been  satisfactorily  explained.  It  has  been 

*  For  a  description  of  results  and  the  literature  see  Porter,  " Journal  of 
Physiology,"  15,  121,  1893;  also  "Journal  of  Experimental  Medicine,"  1,  1, 
1896. 

t  Cushny,  "American  Journal  of  the  Medical  Sciences,"  June,  1911. 


THE    HEART    BEAT.  567 

suggested,  on  the  one  hand,  that  it  is  due  to  some  alteration  in  the 
normal  process  of  conduction,  the  interposition  of  partial  or  com- 
plete blocks  in  the  course  of  the  excitation  wave,  and,  on  the  other, 
that  it  is  caused  by  the  independent  formation  of  impulses  in 
many  foci  throughout  the  cardiac  musculature. 


CHAPTER  XXIX. 

THE  CAUSE  AND  THE  SEQUENCE  OF  THE  HEART 
BEAT— PROPERTIES  OF  THE  HEART  MUSCLE. 

General  Statement. — The  cause  of  the  heart  beat  has  naturally 
constituted  one  of  the  fundamental  objects  of  physiological  inquiry. 
The  various  views  that  have  been  proposed  in  different  centuries 
reflect  more  or  less  accurately  the  advancement  of  the  science. 
With  each  new  discovery  of  general  significance  a  new  point  of  view 
is  obtained  and  the  theories  of  the  heart  beat,  like  those  of  the  other 
great  problems  of  physiology,  shift  their  standpoint  from  generation 
to  generation.  The  general  modern  conception  of  this  problem 
is  referred  usually  to  Haller  (1757),  who  first  taught  that  the 
activity  of  the  heart  is  not  dependent  on  its  connections  with  the 
central  nervous  system.  As  we  shall  see,  the  heart  beat  is  controlled 
and  influenced  constantly  by  the  central  nervous  system,  but  never- 
theless the  important  point  has  been  established  beyond  question 
that  the  heart  continues  to  beat  when  all  these  nervous  connections 
are  severed.  The  central  nervous  system  regulates  the  activity  of 
the  heart,  but  has  nothing  to  do  with  the  cause  of  its  rhythmical 
contractions.  The  heart,  in  other  words,  is  an  automatic  organ. 
When  in  1848  Remak  discovered  that  nerve  cells  are  contained  in 
the  frog's  heart  it  was  natural  that  the  causation  of  the  beat  should 
be  attributed  to  this  tissue.  Subsequent  histological  work  has' 
demonstrated  the  existence  of  numerous  nerve  cells  in  the  substance 
of  the  heart  tissue  of  all  vertebrates,  and  the  view  that  the  au- 
tomaticity  of  the  heart  is  due  in  reality  to  the  properties  of  the 
contained  nerve  cells  was  the  prevalent  view  throughout  the 
middle  and  latter  part  of  the  nineteenth  century.  In  the  latter  part 
of  the  century  an  opposite  view  arose. — namely,  that  the  muscular 
tissue  of  the  heart  itself  possesses  the  property  of  automatic 
rhythmical  contractility.  Both  these  points  of  view  persist  to  day. 
The  theory  that  refers  the  automaticity  of  the  heart  beat  to  the 
contained  nerve  cells  is  designated  as  the  neurogenic  theory  of  the 
heart  beat;  the  one  that  refers  this  property  to  the  muscle  tissue 
itself  is  known  as  the  myogenic  theory.  Beyond  this  question  lies 
the  still  deeper  problem  of  the  explanation  of  the  automaticity 
itself,  the  cause  or  causes  of  the  rhythmical  excitation,  whether 
occurring  primarily  in  the  muscle  cells  or  in  the  nerve  cells. 

568 


PROPERTIES    OF    THE    HEART    MUSCLE.  569 

The  dividing  line  between  the  ancient  and  the  modern  views  of  the  heart 
beat  is  found  in  the  work  of  William  Harvey  (1628).  Before  his  time  physi- 
cians thought  along  the  lines  laid  down  by  the  ancient  masters,  Hippocrates, 
Aristotle,  and  Galen,  in  that  they  believed  that  the  diastole  of  the  heart  is 
the  active  part  of  the  beat.  They  believed  that  the  heart  dilated  at  the  mo- 
ment of  the  apex  beat,  the  dilatation  being  due  to  the  implanted  heat,  the 
vital  spirits,  a  special  pulsatile  force,  etc.  The  arteries  dilated  at  the  same 
time  for  a  similar  reason.  For  a  period  of  over  two  thousand  years  men's 
minds  were  so  chained  to  this  belief  that  they  apparently  could  take  no  other 
view.  Harvey,  however,  had  the  boldness  and  originality  to  look  at  the 
matter  differently.  He  saw  and  proved  that  the  active  movement  of  the  heart 
is  a  contraction  during  systole,  which  drives  blood  out  of  the  ventricles  into  the 
arteries,  and  consequently  that  the  pulse  of  the  arteries  is  not  due  to  their 
active  dilatation,  but  to  a  distension  by  the  blood  forced  into  them.  Harvey 
may  be  considered  also  as  the  founder  of  the  myogenic  theory  of  the  heart 
beat.  For  although  he  did  not  speculate  concerning  the  cause  of  the  beat, 
he  taught  that  the  systole  is  an  active  contraction  of  the  heart's  own  muscu- 
lature not  dependent  upon  any  external  influence.  In  the  same  century  the 
first  neurogenic  hypothesis  was  formulated.  Willis  conceived  that  the  cere- 
bellum controls  the  activity  of  the  involuntary  organs,  including  the  heart. 
The  animal  spirits  engendered  in  the  cerebellum  were  conveyed  to  the  heart 
by  the  vagus  nerve  and  caused  its  beat.  Borelli  formulated  a  somewhat 
different  view.  According  to  him  the  nerve  juice,  succus  spirituosus,  elabo- 
rated in  the  central  nervous  system  was  transmitted  to  the  heart  through  the 
cardiac  nerves  and,  distilling  slowly  into  the  musculature,  set  up  an  ebullition 
which  caused  an  active  expansion  of  the  fibers.  This  expansion  constituted 
the  systole  and  drove  the  blood  out  of  the  heart.  Both  of  these  views  were 
disproved  or  rendered  improbable  largely  by  the  work  of  Haller,  who  in  1757 
published  the  second  myogenic  theory  in  a  form  which,  somewhat  modified, 
prevails  to-day.  Haller  believed  that  the  contraction  of  the  heart  is  due  to  the 
inherent  irritability  of  its  musculature,  and  that  the  venous  blood  as  it  enters 
the  heart  stimulates  it  to  contraction.  Haller's  views  were  generally  accepted 
for  some  years,  but  some  physiologists  continued  to  believe  that  the  heart  beat 
is  controlled  directly  by  the  central  nervous  system.  This  theory  found  its 
most  definite  expression  in  the  work  of  Legallois,  1812,  who  advanced  what 
may  be  called  the  second  neurogenic  hypothesis.  From  experiments  made 
upon  animals  he  concluded  that  the  principle  or  force  that  causes  the  heart 
beat  is  formed  in  the  spinal  cord,  in  all  of  its  parts,  and  reaches  the  heart 
through  the  branches  of  the  sympathetic  nerve  supplying  this  organ.  Legallois's 
conclusions  were  soon  shown  to  be  erroneous,  but  the  general  view  advocated 
by  him  was  entertained  by  some  as  late  as  the  middle  of  the  19th  century, 
in  fact  until  experimental  physiology  had  demonstrated  the  true  functions 
of  the  vagus  and  accelerator  nerves  with  reference  to  the  heart.  Toward  the 
middle  of  the  19th  century  a  third  form  of  neurogenic  hypothesis  arose,  which 
in  the  beginning  seems  to  have  been  due  to  the  work  or  the  system  of  Bichat. 
According  to  this  author  the  ganglionic  or  sympathetic  system  supplies  the 
tissues  of  the  organic  life,  meaning  thereby  the  visceral  organs  which  are  not 
under  the  direct  influence  of  the  will.  In  1844  Remak  discovered  that  the 
heart  possesses  intrinsic  nerve  ganglia,  and  this  fact  seems  to  have  induced  most 
physiologists  to  believe  that  these  ganglia  constitute  a  motor  center  for  the 
heart,  initiating  and  co-ordinating  its  beat.  For  a  period  of  forty  years  this 
form  of  the  neurogenic  hypothesis  enjoyed  almost  universal  acceptance.  In 
1881-83  Gaskell  published  experiments  upon  the  heart  of  the  frog  and  tortoise 
in  which  he  gave  strong  reasons  for  believing  that  the  beat  is  myogenic  in 
origin,  and  that  the  intrinsic  .ganglia  are  simply  a  part  of  the  inhibitory  ap- 
paratus of  the  heart.  Since  that  time  many  physiologists  have  adopted  the 
myogenic  view,  and  the  current  arguments  tending  to  support  this  rather  than 
the  neurogenic  hypothesis  are  presented  in  the  text.  The  most  significant 
addition  to  our  knowledge  of  the  cause  of  the  heart  beat  made  during  the 
last  quarter  of  a  century  is  the  discovery  that  the  inorganic  salts  of  the  blood 
and  lymph  play  a  special  and  essential  role.  The  facts  bearing  upon  this 
interesting  discovery  are  sufficiently  described  in  the  text. 


570  CIRCULATION    OF    BLOOD    AND    LYMPH. 

The  Neurogenic  Theory  of  the  Heart  Beat. — The  literature 
upon  this  topic  is  very  large.*  The  neurogenic  theory  has  suffered 
some  changes  in  its  details  since  first  proposed  by  Volkmann, 
particularly  in  the  specific  functions  assigned  to  the  different  ganglia 
that  exist  in  the  heart.  In  general,  however,  the  theory  assumes 
that  the  excitation  to  each  beat  arises  within  the  nerve  cells,  and 
since  the  cardiac  cycle  begins  with  a  contraction  at  what  may  be 
called  the  venous  end  of  the  heart, — that  is,  at  the  junction  of  the 
veins  with  the  auricles, — it  is  assumed  that  the  excitation  or  inner 
stimulus  arises  in  the  nerve  cells  situated  in  this  region.  These  cells 
constitute,  therefore,  what  may  be  called  the  automatic  motor 
center  of  the  heart.  The  stimuli  generated  within  it  are  transmitted 
through  its  axons  first  to  the  musculature  of  the  venous  end  of 
the  heart.  The  subsequent  orderly  march  of  this  contraction,  to 
auricles  and  then  to  ventricles,  is  also  upon  this  theory  usually 
attributed  to  the  intrinsic  nerve  cells  and  fibers.  Through  a  definite 
mechanism  the  impulses  generated  in  the  motor  center  are  trans- 
mitted to  subordinate  nerve  centers  through  which  the  auricles  are 
excited,  and  then  to  other  nerve  cells  lying  in  or  near  the  auriculo- 
ventricular  groove  or  to  the  nervous  tissue  in  the  auriculoven- 
tricular  bundle  through  which  the  ventricles  are  excited.  In  this 
form  the  theory  assumes  for  the  heart  an  intrinsic  central  nerv- 
ous system,  as  it  were,  with  a  principal  motor  center  in  which 
the  property  of  automaticity  is  chiefly  developed  and  subordinate 
centers  whose  activity  usually  depends  upon  the  principal  center, 
but  which  may  show  automatic  properties  of  a  lower  order  if  the 
connections  between  them  and  the  main  center  are  interrupted. 
This  intrinsic  nervous  system  is  responsible  not  only  for  the  spon- 
taneous origination  and  normal  sequence  of  the  beat,  but  also  for 
its  co-ordination.  The  many  muscular  fibers  of  the  ventricle 
contract  normally  in  a  definite  manner  and  sequence,  so  that  their 
effect  is  summated.  Under  abnormal  conditions  the  fibers  may 
contract  irregularly,  giving  the  so-called  fibrillary  contractions  of 
the  heart,  which  are  incorordinated.  It  may  be  said  that  this  con- 
ception of  the  connections  of  the  intrinsic  nervous  system  rests 
mainly  upon  deductions  from  physiological  experiments.  The 
histological  details  regarding  the  connections  of  the  nerve  cells  in  the 
heart  are  not  yet  sufficiently  known,  but  it  can  not  be  said  at  present 
that  they  give  any  positive  support  to  such  a  view.  In  regard  to 
the  neurogenic  theory  the  following  general  statements  may  be  made : 

1.  Most  of  the  very  numerous  facts  known  regarding  the  heart 

*  For  general  presentations  from  different  standpoints  see  Gaskell,  article 
on  "The  Contraction  of  Cardiac  Muscle,"  in  Schafer's  "Text-book  of  Physi- 
ology," vol.  ii,  1900;  Langendorff,  "Herzmuskel  und  intrakardiale  Innerva- 
tion"  in  "Ergebnisse  der  Physiologic,"  vol.  i,  part  n,  1902;  and  Cyon,  "L'inner- 
vation  du  coeur,"  Richet's  "Dictionnaire  du  Physiologic,"  vol.  iv,  1900;  Flack, 
in  Hill's  "Further  Advances  in  Physiology,"  1909,  53. 


PROPERTIES    OF    THE    HEART    MUSCLE.  571 

beat  and  its  variations  under  experimental  conditions  may  be 
explained  in  terms  of  the  theory,  or  at  least  do  not  contradict  it. 
The  same  statement,  however,  may 'be  made  regarding  the  myogenic 
theory.  Both  theories  may  be  applied  successfully  from  a  logical 
standpoint  to  the  explanation  of  known  facts. 

2.  No  single  fact  is  known  which  can  be  cited  as  positive  proof 
that  -the  nerves  participate  in  the  production  of  the  normal  beat 
of  the  vertebrate  heart.  The  experiment  by  Kronecker  and  Schmey 
is  sometimes  given  this  significance.  These  observers  have  shown 
that,  when  a  needle  is  thrust  into  a  certain  spot  in  the  dog's 
ventricle,  the  regularly  contracting  heart  falls  suddenly  into  fibril- 
lary  contractions  so  far  as  the  ventricles  are  concerned.  The  ex- 
periment is  certainly  a  striking  and  interesting  one.  The  needle 
may  be  thrust  many  times  into  certain  portions  of  the  muscular 
mass  without  affecting  the  powerful  co-ordinated  contractions, 
but  in  the  region  specified  by  Kronecker  a  single  puncture,  if  it 
reaches  the  right  spot,  causes  the  ventricle  to  fall  into  irregular 
fibrillary  twitches  from  which  it  does  not  recover.  The  spot 
as  described  by  Kronecker  is  along  the  line  of  the  septum  at  the 
lower  border  of  its  upper  third.  The  experiment  frequently  fails; 
and  it  would  seem  that  there  must  be  a  definite  and  quite  circum- 
scribed structure  whose  lesion  produces  the  effect  described.  We 
have  no  evidence  as  yet  what  this  structure  is,  and  are  therefore  in 
no  condition  to  make  positive  inferences  with  regard  to  the  bearing 
of  the  experiment  upon  the  origin  of  the  heart  beat.  Carlson* 
has  described  experiments  upon  the  heart  of  the  horseshoe  crab 
(Limulus)  which  seem  to  show  conclusively  that  in  this  animal 
the  rhythmical  contractions  are  dependent  upon  the  intrinsic  nerve 
cells.  These  latter  are  placed  superficially,  forming  a  cord  that 
runs  the  length  of  the  tubular  heart.  When  this  cord  is  removed 
the  heart  ceases  to  beat.  There  are  reasons,  however,  which  at 
present  make  it  doubtful  whether  we  can  apply  the  results  of  this 
experiment  to  the  vertebrate  heart.  The  crustacean  heart  differs 
from  the  vertebrate  heart  in  its  fundamental  properties;  unlike  the 
latter,  it  has  no  refractory  period  (see  p.  579) ,  can  be  tetanized,  and 
gives  submaximal  contractions.!  It  is  a  tissue,  therefore,  that 
resembles  in  its  properties  ordinary  skeletal  muscle  in  the  verte- 
brate, and,  like  this  muscle,  it  seems  to  be  lacking  in  automaticity. 
Carlson's  experiments  give,  however,  another  instance  of  automatic 
rhythmicity  in  nerve  tissue,  and  to  that  extent  support  the  neuro- 
genie  theory. 

The  Myogenic  Theory  of  the  Heart  Beat. — The  myogenic 
theory  has  been  developed  chiefly  by  Gaskell  and  by  Engelmann. 
It  assumes  that  the  heart  muscle  itself  possesses  the  property  of 
automatic  rhythmicity  and  that  this  property  is  most  highly 

*  Carlson,  "American  Journal  of  Physiology,"  12,  67,  and  471,  1905. 
fHunt,  Bookman,  and  Tierney,  "Centralbl.  f.  Physiologie,"  11,  275, 1897. 


572  CIRCULATION    OF    BLOOD    AND    LYMPH. 

developed  at  the  venous  end,  according  to  recent  views  in  that 
remnant  of  sinus  tissue  known  as  the  sino-auricular  node.  This 
portion  of  the  heart,  therefore,  contracts  first  and  the  wave  of 
contraction  spreads  directly  to  the  musculature  of  the  auricle  and 
thence  through  the  auriculo-ventricular  bundle  to  that  of  the 
ventricle.  The  quickly  beating  venous  end  sets  the  pace,  as  it 
were,  for  the  entire  heart.  The  nerve  cells  and  nerve-fibers  that 
are  present  in  the  heart  are  upon  this  theory  supposed  to  be  con- 
nected with  the  extrinsic  nerves  through  which  the  rate  and  force 
of  the  heart  beat  are  regulated,  but  they  are  not  concerned  in  the 
production  of  the  beat.  Many  experimental  facts  have  been  ac- 
cumulated which  give  probability  to  this  view,  and  it  has  been 
adopted  by  many,  perhaps  most,  of  the  recent  workers  in  this 
field.  Some  of  the  facts  that  favor  this  theory  are  as  follows: 

1.  The   anatomical   arrangement  of  the   musculature   of   the 
heart  is  not  opposed  to  such  a  theory.     It  was  formerly  stated  quite 
positively  that  there  is  no  muscular  connection  between  the  auricles 
and  ventricles  in  the  mammalian  heart,  but  we  now  know  that 
these  two  parts  of  the  heart  are  connected  through  a  peculiar 
system  of  muscular  tissue,  the  auriculoventricular  bundle  and  its 
ramifications.     It  may  be  accepted  also  that  the  wave  of  excitation 
from  the  sinus  end  of  the  heart  passes  along  this  system.     All  the 
detectable  nerve  trunks  crossing  the  auriculoventricular  groove 
may  be  cut  without  altering  the  sequence  of  the  heart  beat,  but 
section  or  compression  of  the  A-V  bundle  brings  on  at  once  the 
condition   of   dissociated   heart-rhythm   known   as   heart   block. 
The  auriculoventricular  bundle  contains  nerve-fibers  as  well  as 
muscle-fibers,   and  the  advocates  of  the  neurogenic  hypothesis 
make,  therefore,  the  somewhat  improbable  claim  that  these  par- 
ticular nerve-fibers  of  all  those  that  pass  between  auricle  and  ven- 
tricle are  the  only  ones  concerned  in  the  conduction  of  the  normal 
stimulus  from  auricle  to  ventricle. 

2.  The  fact  that  a  contraction  started  at  one  part  of  the  heart 
may  travel  to  other  portions  through  the  intervening  musculature 
may  be  said  to  be  demonstrated.     Thus,  Engelmann  has  shown 
that  if  the  ventricle  in  the  frog's  heart  is  cut  in  a  zigzag  fashion, 
so  that  strips  are  obtained  which  are  connected  only  by  narrow 
bridges,  a  stimulation  applied  at  one  end  starts  a  wave  of  con- 
traction which  propagates  itself  over  all  of  the  pieces.     This  and 
similar  experiments  scarcely  permit  of  explanation  on  the  supposi- 
tion that  conduction  from  piece  to  piece  is  effected  by  a  definite 
nervous  mechanism.     So  too  it  has  been  shown  that  under  certain 
conditions  the  normal  auriculo-ventricular  rhythm  can  be  changed 
at  will  to  a  ventriculo-auricular  rhythm.     If,  for  instance,  a  ligature 
be  tied  around  the  frog's  heart  between  the  sinus  venosus  and  the 


PROPERTIES    OF    THE    HEART   MUSCLE.  573 

auricle  (first  ligature  of  Stannius)  the  auricle  and  ventricle  ceaso 
to  beat.  In  this  quiescent  condition  a  slight  mechanical  stimulus 
to  the  ventricle  causes  it  to  beat  and  its  contraction  is  immediately 
followed  by  that  of  the  auricle.  A  similar  reversed  rhythm  may  be 
obtained  from  the  mammalian  heart  under  suitable  conditions. 
Such  an  experiment  makes  it  most  probable  that  the  contraction 
is  propagated  from  one  chamber  to  the  other  directly  through 
the  muscular  connections.  It  is  not  possible  at  present  to  conceive 
that  a  definite  mechanism  of  neurons  should  work  thus  in  either 
direction. 

3.  There  is  much  probable  proof  that  the  heart  muscle  tissue 
possesses  the  property  of  automatic  rhythmical  contractions.     Ex- 
periments, initiated  by  Gaskell  and  since  extended  by  numerous 
observers,  show  that  in  the  cold-blooded  animals  strips  of  heart 
muscle  taken  from  various  parts  of  the  heart  will  under  proper 
conditions  develop  rhythmical  contractions.    It  is  very  improbable 
that  each  of  these  strips,  no  matter  how  made,  contains  its  own 
resident  nerve  cells  or  nerve  tissue  which  act  as  a  motor  center. 
These  results  seem  to  demonstrate  an  inherent  property  of  rhythm- 
icity  in  cardiac  muscle,  whether  or  not  this  rhythmicity  is  directly 
responsible  for  the  normal  beat. 

4.  It  has  been  shown  that  in  the  embryo  chick  the  heart  pul- 
sates normally  before  the  nerve  cells  have  grown  into  it.     More 
recently  it  has  been  demonstrated  that  portions  of  the  heart- 
muscle  may  be  removed  from  the  embryo  and  be  kept  alive  in  a 
blood-plasma  medium*.     Isolated  pieces  of  this  kind  continue  to 
beat  and  to  undergo  multiplication  and  differentiation,  giving  rise 
to   isolated   muscle-cells  which    exhibit    rhythmic    contractility. 
This  result  indicates  very  clearly  that  the  embryonic  heart  muscle 
is  capable  of  automatic  contractility.     It  is  possible  of  course 
that  at  a  later  stage  of  development  this  property  may  be  lost  by 
the  muscle,  but  it  is  perhaps  more  probable  that  the  property  is 
retained  in  some  degree  throughout  life,  the  greatest  power  of 
rhythmicity  being  exhibited  by  the  least  differentiated  tissue  in 
the  venous  end  of  the  heart,  the  sino-auricular  node,  in  which  the 
heart  beat  originates. 

Automaticity  of  the  Heart. — As  was  said  above,  the  ques- 
tion of  the  cause  or  causes  of  the  automatic  rhythmical  con- 
tractions must  be  sought  for  whether  the  phenomenon  turns  out  to 
be  a  property  of  the  muscular  tissue  or  of  the  nervous  tissue  of  the 
heart.  When  we  say  that  a  given  tissue  is  automatic  we  mean 
that  the  stimuli  which  excite  it  to  activity  arise  within  the  tissue 
itself,  and  are  not  brought  to  it  through  extrinsic  nerves.  In  the 
heart,  therefore,  we  assume  that  a  stimulus  is  continually  being 
*  Burrows,  "Science,"  36,  90,  1912. 


574  CIRCULATION    OF    BLOOD    AND    LYMPH. 

produced,  and  we  speak  of  it  as  the  inner  stimulus.  Experiment  and 
speculation  have  been  directed  toward  unraveling  the  nature  of 
this  inner  stimulus.  Most  of  the  physiologists  who  have  expressed 
an  opinion  upon  the  subject  have  sought  an  explanation  in  the 
composition  of  the  blood  or  lymph  bathing  the  heart  tissue,  or  in  the 
products  of  metabolism  of  the  tissue  itself.  Regarding  this  latter 
view  there  is  nothing  of  the  nature  of  direct  experimental  evidence 
in  its  favor.  No  product  of  the  metabolism  of  the  heart  tissue 
capable  of  exerting  this  stimulating  effect  has  been  isolated.  In 
regard  to  the  former  view,  that  the  inner  stimulus  is  connected 
with  a  definite  composition  of  the  blood  or  lymph,  there  has  been 
considerable  experimental  work  which  is  of  fundamental  signifi- 
cance. While  the  older  physiologists  paid  attention  mainly  to  the 
organic  substances  in  the  blood,  it  has  been  shown  in  recent  years 
that  the  inorganic  salts  are  the  elements  whose  influence  upon 
the  heart  beat  is  most  striking.  These  salts  are  in  solution  in  the 
liquid  of  the  tissue,  and  are  therefore  probably  more  or  less  com- 
pletely dissociated.  Attention  has  been  directed  mainly  to  the 
influence  of  the  cations,  of  which  three  are  especially  important, 
— namely,  the  sodium,  the  calcium,  and  the  potassium. 

The  Action  of  the  Calcium,  Potassium,  and  Sodium  Ions  in 
the  Blood  and  Lymph. — It  has  long  been  known  that  the  heart 
of  a  frog  or  terrapin  may  be  kept  beating  normally  for  hours  after 
removal  from  the  body,  provided  it  is  supplied  with  an  artificial 
circulation  of  blood  or  lymph,  so  arranged  that  this  liquid  enters 
the  heart  through  the  veins  from  a  reservoir  of  some  sort  and  is 
pumped  out  through  the  arteries  leading  from  the  ventricle.  It 
was  first  shown  by  Merunowicz,  working  under  Ludwig's  direction, 
that  an  aqueous  extract  of  the  ash  of  the  blood  possesses  a  similar 
action. 

Ringer  afterwards  proved  that  the  frog's  heart  can  be  kept 
beating  for  long  periods  upon  a  mixture  of  sodium  chlorid,  potassium 
chlorid,  and  calcium  phosphate  or  chlorid,  and  he  laid  especial 
stress  upon  the  importance  of  the  calcium.  This  work  was  after- 
wards confirmed  and  extended  by  others,  who  attempted  to 
analyze  the  part  played  by  the  several  ions.*  If  a  frog's  or  a 
terrapin's  heart  is  fed  with  a  solution  of  physiological  saline 
(NaCl,  0.7  per  cent.)  it  beats  well  for  a  while,  but  the  beats 
soon  weaken  and  gradually  fade  out.  If  in  this  condition  the 
heart  is  fed  with  a  proper  mixture  of  sodium,  potassium,  and 
calcium  chlorids  it  beats  vigorously  and  well  for  very  many 

*  For  literature  and  discussion  see  Ho  well,  "American  Journal  of  Phys- 
iology," 2,  47,  1898,  and  6,  181,  1901,  and  "Journal  of  the  American  Medical 
Association,"  1906.  Burridge,  "Quarterly  Journal  of  Exp.  Physiology,"  5, 
347,  1912. 


PROPERTIES    OF    THE    HEART    MUSCLE.  575 

hours.  A  solution  containing  these  three  salts  in  proper  propor- 
tions is  known  usually  as  Ringer's  mixture.  The  exact  com- 
position has  been  varied  by  different  workers,  but  for  the  heart 
of  the  frog  or  terrapin  the  following  composition  is  most  effective: 

NaCl  .   =  0.7      percent. 

KC1  .  =  0.03     "       " 

CaCl =  0.025   " 

The  addition  of  a  trace  of  alkali,  HNaCO3,  0.003  per  cent., 
often  increases  the  effectiveness  of  the  solution,  but  it  cannot  be 
considered  an  essential  constituent  in  the  same  sense  as  sodium, 
potassium,  and  calcium.  It  has  been  shown,  moreover,  that  even 
the  mammalian  heart  can  be  kept  beating  for  long  periods  when 
fed  with  a  Ringer  solution  if  provision  is  made  for  a  larger  supply 
of  oxygen  than  can  be  obtained  by  simple  exposure  to  the  air. 
For  the  irrigatiDn  of  the  isolated  mammalian  heart  different 
forms  of  Ringer's  solution  have  been  employed,  but  the  mixture 
most  frequently  used  is  that  recommended  by  Locke,  consisting 
of  NaCl,  0.9  per  cent.;  CaCl2,  0.024  per  cent.;  KC1,  0.042  per 
cent.;  NaHCO3,  0.01  to  0.03  per  cent.;  and  dextrose,  0.1  per  cent. 
The  solution  is  fed  to  the  heart  under  an  atmosphere  of  oxygen, 
and  with  this  solution  Locke  and  others  have  kept  the  mammalian 
heart  beating  for  many  hours.  The  dextrose,  while  not  essential 
to  the  action  of  the  irrigating  liquid,  increases  its  efficiency,  and 
Locke*  has  shown  that  the  sugar  is  apparently  utilized  by  the 
heart,  since  a  considerable  amount  disappears  from  the  solution 
when  the  heart  is  beating  strongly.  The  general  fact  that  comes 
out  of  these  experiments  is  that  the  heart  caa  beat  for  very  long 
periods  upon  what  has  been  called  an  inorganic  diet.  Moreover, 
the  salts  that  are  used  cannot  be  chosen  at  random ;  it  is  necessary 
to  have  salts  of  the  three  metals  named,  and  substitution  is  possible 
only  to  a  very  limited  extent.  Thus,  strontium  salts  may  replace 
those  of  calcium  more  or  less  perfectly. 

It  is  evident  that  these  salts  play  some  very  important  part 
in  the  production  of  the  rhythmical  beat  of  the  heart;  and  analysis 
has  shown  that  the  sodium,  calcium,  and  potassium  has  each 
its  special  role.  We  may  say  that  the  presence  of  these  salts 
in  normal  proportions  is  an  absolute  necessity  for  heart  activity. 
A  striking  experiment  which  shows  the  importance  of  the  calcium 
is  to  irrigate  a  terrapin's  heart  with  blood-serum  from  which  the 
calcium  has  been  removed  by  precipitation  with  sodium  oxalate. 
In  spite  of  the  fact  that  all  other  constituents  of  the  blood  are 
present  the  heart  ceases  to  beat,  and  normal  contractions  can  be 

*  Locke  and  Rosenheim,  "Journal  of  Physiology,"  36,  205,  1907.  See  also 
Knowlton  and  Starling,  ibid.  45,  146,  1912. 


576  CIRCULATION    OF    BLOOD    AND    LYMPH. 

started  again  promptly  by  adding  calcium  chlorid  in  right  amounts 
to  the  oxalated  blood.  Regarding  the  specific  part  taken  by  each 
of  the  cations  in  the  production  of  the  alternate  contractions  and 
relaxations,  much  diversity  of  opinion  exists,  owing  to  our  ignorance 
of  the  chemical  changes  going  on  in  the  heart  during  systole  and 
diastole  and  to  the  difficulty  of  controlling  experimental  conditions. 
Thus,  while  it  is  an  easy  matter  to  control  accurately  the  com- 
position of  the  liquids  supplied  to  the  heart,  a  variable  and  uncon- 
trollable factor  is  ^introduced  by  the  fact  that  within  the  tissue 
elements  themselves  there  is  a  store  of  combined  calcium,  potas- 
sium, and  sodium  which  may  serve  to  supply  these  elements  to  a 
greater  or  less  extent  to  the  tissue  liquids. 

The  controversial  details  upon  this  question  cannot  be  presented 
in  an  elementary  book,  but  the  following  brief  statements  may 
be  made  regarding  one  view  of  the  specific  effects  of  the  separate 
cations:  (1)  The  sodium  salts  in  the  blood  and  lymph  take  the 
chief  part  in  the  maintenance  of  normal  osmotic  pressure.  The 
sodium  chlorid  exists  in  blood-plasma  to  the  extent  of  0.5  to  0.6 
per  cent.,  and  the  normal  osmotic  pressure  of  the  blood  is  mainly 
dependent  upon  it.  A  solution  of  sodium  chlorid  of  0.7  to  0.9  per 
cent,  forms  what  is  known  as  physiological  saline,  and  although 
not  adequate  to  maintain  the  normal  composition  and  properties 
of  the  tissues  it  fulfills  this  purpose  more  perfectly  than  the  solution 
of  any  other  single  substance.  The  sodium  ions  have  in  addition 
a  specific  influence  upon  the  state  of  the  heart  tissue.  Contractility 
and  irritability  disappear  when  they  are  absent;  when  present  alone, 
in  physiological  concentration,  in  the  medium  bathing  the  heart  mus- 
cles they  produce  relaxation  of  the  muscle  tissue.  (2)  The  calcium 
ions  are  present  in  relatively  very  small  quantities  in  the  blood,  but 
they  also  are  absolutely  necessary  to  contractility  and  irritability. 
When  present  in  quantities  above  normal  or  when  in  a  propor- 
tional excess  over  the  sodium  or  potassium  ions  they  cause  a  con- 
dition of  tonic  contraction  that  has  been  designated  as  calcium 
rigor.  (3)  The  potassium  ions  are  present  also  in  very  small  quan- 
tities, and,  unlike  the  calcium  and  sodium  ions,  their  presence  in 
the  circulating  liquid  does  not  seem  to  be  absolutely  necessary  to 
rhythmical  activity.  Under  proper  conditions  a  terrapin's  heart 
beats  well  for  a  time  upon  a  solution  containing  only  sodium  and 
calcium  salts.  The  potassium  seems  to  promote  relaxation  of  the 
muscle  and  in  physiological  doses  it  exercises  through  this  effect 
a  regulating  influence  upon  the  rate  of  beat.  When  the  proportion 
of  potassium  ions  is  increased  the  heart  rate  is  proportionally 
slowed,  and  finally  the  contractions  cease  altogether,  the  heart 
coming  to  rest  in  a  state  of  extreme  relaxation,  known  sometimes 
as  potassium  inhibition.  (4)  It  appears  from  these  statements 


PROPERTIES    OF    THE    HEART    MUSCLE.  577 

that  there  is  a  well-marked  antagonism  between  the  effects  of  the 
calcium,  on  the  one  hand,  and  the  potassium  and  sodium,  on  the 
other.  The  calcium  promotes  a  state  of  contraction,  the  sodium 
and  the  potassium  a  state  of  relaxation.  It  is  conceivable,  there- 
fore, that  the  alternate  states  of  contraction  and  relaxation  which 
characterize  the  rhythmical  action  of  heart  muscle  are  connected 
in  some  way  with  an  interaction  of  an  alternating  kind  between 
these  ions  and  the  living  contractile  substance  of  the  heart.  It  is 
impossible  to  say  positively  whether  or  not  the  inorganic  salts 
are  directly  connected  with  the  cause  of  the  beat, — that  is,  with 
the  origination  of  the  inner  stimulus.  According  to  one  point  of 
view,  they  are  necessary  only  to  the  irritability  and  contractility 
of  the  heart  tissue.  The  inner  stimulus  is  produced  otherwise  by 
some  unknown  reaction,  but  it  is  not  able  to  cause  a  contraction 
of  the  heart  muscle  in  the  absence  of  the  proper  inorganic  salts. 
According  to  another  view,  the  reaction  of  these  ions  with  the 
living  substance  constitutes  or  leads  to  the  development  of  the 
inner  stimulus. 

Physiological  Properties  of  Cardiac  Muscle. — Cardiac  muscle 
exhibits  certain  properties  which  distinguish  it  sharply  from  skeletal 
muscular  tissue  and  which  have  a  direct  bearing  upon  the  rhyth- 
micity  of  the  contractions  and  the  sequence  shown  by  the  different 
chambers.  The  most  characteristic  of  these  properties  are  the 
following: 

1.  The  contractions  of  heart  muscle  are  always  maximal.  In 
skeletal  muscle  and  in  plain  muscle  .the  extent  of  contraction  is 
related  to  the  strength  of  the  stimulus,  and  we  recognize  the  exis- 
tence of  a  series  of  submaximal  contractions  of  varying  heights. 
This  is  not  true  of  heart  muscle.  As  was  first  shown  by  Bow- 
ditch,  a  piece  of  ventricular  muscle  when  stimulated  responds,  if 
it  responds  at  all,  with  a  maximal  contraction.  The  apex  of  a 
frog's  heart  does  not  beat  spontaneously,  but  contracts  upon 
electrical  stimulation.  If  such  an  apex  is  connected  with  a  lever 
to  register  its  contractions,  and  the  electrical  stimulus  applied  to 
it  is  gradually  increased,  the  first  contraction  to  appear  is  maxi- 
mal, and  it  is  not  further  increased  by  augmenting  the  stimulus. 
This  property  is  sometimes  described  by  saying  (Ranvier)  that 
the  contraction  of  the  heart  muscle  is  all  or  none.  This  fact 
must  not,  however,  be  interpreted  to  mean  that  the  force  of 
contraction  of  heart  muscle  is  invariable  under  all  conditions. 
Such  is  not  the  case.  The  heart  muscle  under  favorable  nutritive 
conditions  may  give  a  much  larger  and  more  forcible  contraction 
than  is  possible  under  conditions  of  poor  nutrition;  but  the  point 
is,  that,  whatever  may  be  the  condition  of  the  muscle  at  any 
given  moment,  its  contraction  in  response  to  artificial  stimulation 
37 


578 


CIRCULATION    OF   BLOOD    AND    LYMPH. 


is  maximal  for  that  condition, — that  is,  does  not  vary  with  the 
strength  of  the  stimulus.    As  was  said  above,  this  property  is  not 


Fig  236.— To  show  the  effect  of  a  short  electrical  stimulus  applied  at  different  times 
in  the  heart  beat.— (Marey.)  The  record  is  taken  from  the  frog's  heart.  In  1,  2,  and  3  the 
stimulus  (e)  falls  into  the  heart  during  systole  (refractory  period)  and  has  no  effect.  In 
4,  5,  6,  7,  and  8  the  stimulus  falls  into  the  heart  toward  the  end  of  systole  or  during  diastole, 
and  is  followed  by  an  extra  systole  and  corresponding  compensatory  pause, 
noted  that  the  latent  period  (shaded  area)  between  the  stimulus  and  the  extra  systole  w 
ahorter  the  longer  the  diastole  has  preceded  before  the  stimulus  is  applied. 


PROPERTIES    OF    THE    HEART    MUSCLE.  579 

exhibited  by  the  crustacean  (lobster)  heart,  but  has  been  shown 
to  be  true  for  the  mammalian  heart  muscle.*  It  will  be  remem- 
bered (p.  29)  that,  according  to  some  authors,  the  difference  in 
this  respect  between  skeletal  muscle  and  heart  muscle  is  only  ap- 
parent and  due  to  the  fact  that  in  the  former  the  fibers  are  separated 
from  one  another  by  the  sarcolemmal  sheaths.  They  hold  that  in 
skeletal  as  well  as  in  heart  muscle  the  contraction  of  each  fiber  is 
all  or  none,  and  that  so-called  submaximal  contractions  are  simply 
contractions  in -which  less  than  the  whole  number  of  fibers  partici- 
pate. 

2.  The  refractory  period  of  the  beat.  It  was  shown  by  Marey  f  that 
the  heart  muscle  is  irritable  to  artificial  (electrical)  stimuli  only 
during  the  period  of  diastole.  During  the  period  of  systole  an  elec- 
trical stimulus  has  no  effect;  during  the  period  of  diastole  such  a 
stimulus  calls  forth  an  extra  systole  and  the  latent  period  pre- 
ceding the  extra  contraction  is  shorter  the  later  the  stimulus  is 
applied  in  the  diastolic  phase.  This  relationship  is  well  shown  by 
Marey's  curves  reproduced  in  Fig.  236.  The  period  of  inexcitabil- 
ity  is  designated  as  the  refractory  period  of  the  heart  beat.  Marey 
defined  this  refractory  period  as  falling  within  the  first  part  of  the 
systole,  and  stated  that  its  duration  varies  with  the  actual  strength 
of  the  stimulus.  Later  experiments  by  other  investigators  make  it 
probable  that  the  refractory  period  lasts  during  practically  the  entire 
systole.it  According  to  this  point  of  view,  therefore,  the  heart  muscle 
during  its  period  of  actual  contraction  is  entirely  unirritable,  and  in 
this  respect  it  offers  a  striking  difference  to  skeletal  and  plain  muscle. 
The  existence  of  this  refractory  period  explains  why  the  heart 
muscle  cannot  be  thrown  into  complete  tetanic  contractions  by 
rapidly  repeated  stimuli.  Since  each  contraction  is  accompanied 
by  a  condition  of  loss  of  irritability,  it  is  obvious  that  those  stimuli 
that  fall  into  the  heart  during  this  period  must  prove  ineffective. 
The  refractory  period  and  the  gradual  increase  in  irritability  during 
the  diastole  may  throw  some  light  also  on  the  rhythmical  character 
of  the  beat.  The  occurrence  of  the  refractory  period  and  the 
subsequent  gradual  return  of  irritability  are  connected  no  doubt 
with  the  metabolic  changes  taking  place  in  the  heart  muscle.  It 
is  in  the  character  of  this  metabolism  that  we  must  seek  for  the 
final  explanation  of  these  two  phenomena  and  the  cause  of  the 
rhythmicity  of  the  contractions.  As  was  stated  above,  it  has  been 
shown  that  the  crustacean  (lobster)  heart  muscle  does  not  obey  the 
all-or-none  law,  is  not  refractory  during  systole,  and  is  capable  of 
giving  tetanic  contractions  when  rapidly  stimulated.  In  all  these 

*  For  experiments  on  mammalian  heart  and  literature,  see  Woodworth, 
"American  Journal  of  Physiology,"  8,  213,  1903. 


f  Marey,  "Travaux  du  laboratoire,"  1876,  p.  73. 

Also 
1908. 


J.UI  \J)      [  '•      I  W« 

t  See  paper  by  Woodworth,  loc.  cit.     Also  Schultz,  "American  Journal, of 
Physiology,"  16,  483,  1906,  and  22,  133, 


580  CIRCULATION    OF    BLOOD    AND    LYMPH. 

respects  it  differs  from  the  typical  heart  muscle  of  the  vertebrate, 
but  the  difference  is  perhaps  sufficiently  explained  by  the  discovery 
(p.  571)  that  the  crustacean  heart,  in  one  form  at  least,  is  not  an 
automatically  rhythmical  tissue.  Its  rhythmical  contractions,  like 
those  of  the  diaphragmatic  muscle  in  the  higher  vertebrates,  depend 
upon  rhythmical  impulses  received  from  nerve  centers. 

The  Compensatory  Pause. — It  has  been  observed  that  when  an  extra 
systole  is  produced  by  stimulating  a  ventricle  it  is  followed  by  a  pause  longer 
than  usual;  the  pause,  in  fact,  is  of  such  a  length  as  to  compensate  exactly 
for  the  extra  beat ;  so  that  the  total  rate  of  beat  remains  the  same.  The  pro- 
longed pause  under  these  conditions  is  therefore  frequently  designated  as  the 
compensatory  pause.  It  has  been  shown,*  however,  that  the  exact  compen- 
sation in  this  case  is  not  referable  to  a  property  of  heart  muscle,  but  is  due  to 
the  dependence  of  the  ventricular  upon  the  auricular  beat.  When  the  auricle 
or  ventricle  is  isolated  and  stimulated  the  phenomenon  of  exact  compensation 
is  not  observed.  In  an  entire  heart,  on  the  contrary,  the  beat  originates  at 
the  venous  end  of  the  auricle  and  is  propagated  to  the  ventricle.  If  the  latter 
chamber  is  stimulated  so  as  to  give  an  extra  beat  out  of  sequence  it  will  remain 
in  diastole  until  the  next  auricular  beat  stimulates  it,  and  will  thus  pick  up 
the  regular  sequence  of  the  heart  beat. 

The  Normal  Sequence  of  the  Heart  Beat. — The  normal 
rhythm  of  the  heart  beat  is  first  a  contraction  of  the  auricles, 
then  one  of  the  ventricles.  Many  efforts  have  been  made  to 
determine  the  precise  spot  in  which  the  contraction  of  the  heart 
normally  starts.  Formerly  it  was  supposed  that  the  contraction 
began  in  the  great  veins  just  before  they  pass  into  the  auricle, 
and  it  was  implied  that  this  initiation  of  the  beat  might  occur  in 
the  pulmonary  veins  as  well  as  in  the  vense  cavae.  More  recent 
experiments  f  which  have  been  made  largely  upon  the  isolated 
heart  while  perfused  with  a  Ringer-Locke  solution  have  shown 
pretty  conclusively  that  the  most  rhythmic  part  of  the  heart 
and  the  part  from  which  the  beat,  in  all  probability,  normally 
starts  is  an  area  of  the  wall  of  the  right  auricle  lying  between 
the  openings  of  the  venae  cavae,  or,  according  to  the  most  recent 
views,  in  that  remnant  of  the  sinus  tissue  known  as  the  sino-auricular 
node  which  lies  in  this  region,  and  which  is  connected  with  the 
auricular  muscle  and  with  the  auriculoventricular  bundle  (p. 
541).  When  this  portion  of  the  heart  is  warmed  or  cooled  the 
rate  of  beat  of  the  whole  heart  is  correspondingly  increased  or 
decreased,  while,  on  the  contrary,  warming  or  cooling  of  the  ven- 
tricles themselves,  the  auricular  appendages,  the  left  auricle,  etc.,  has 
no  effect  upon  the  heart-rate.  From  the  point  of  confluence  of  the 
venae  cavae  the  wave  of  contraction  spreads  over  the  auricles  and 
through  the  auriculoventricular  bundle  to  the  ventricles.  This 
sequence  from  venous  to  arterial  end  is  beautifully  shown  in  the 

*  Cushny  and  Matthews,  "Journal  of  Physiology,"  21,  227,  1897. 

t  Consult  especially  Adam,  "Archiv  f.  d.  ges.  Physiol.,"  Ill,  607,  1906; 
Erlanger  and  Blackman,  "American  Journal  of  Physiology,"  19,  125,  1907, 
and  Flack,  "Journal  of  Physiology,"  41,  64,  1910. 


PROPERTIES    OF    THE    HEART    MUSCLE.  581 

frog's  heart,  in  which  the  contraction  begins  in  the  sinus  venosus, 
spreads  to  the  auricles,  thence  to  the  ventricle,  and  finally 
to  the  bulbus  arteriosus.  Under  normal  conditions  this  sequence 
is  never  reversed,  and  an  explanation  of  the  natural  order 
forms  obviously  an  important  part  of  any  complete  theory 
of  the  heart  beat.  Those  who  hold  to  the  neurogenic  theory 
naturally  explain  the  sequence  of  the  beat  by  reference  to  the 
intrinsic  nervous  apparatus.  If  the  motor  ganglia  lie  toward  the 
venous  end  of  the  heart  one  can  imagine  that  their  discharges  may 
affect  the  different  chambers.,  in  sequence,  the  pause  between 
auricular  and  ventricular  contraction  being  due,  let  us  say,  to  the 
fact  that  the  motor  impulses  to  the'  ventricle  have  to  act  through 
subordinate  nerve  cells  in  the  auriculo-ventricular  region,  and  the 
time  necessary  for  this  action  brings  the  ventricular  contraction 
a  certain  interval  later  than  that  of  the  auricle.  There  is  no 
immediate  proof  or  disproof  of  such  a  view.  The  numerous  exper- 
iments made  upon  the  rapidity  of  conduction  of  the  wave  of 
contraction  over  the  heart  are  not  conclusive  either  for  or  against 
the  view.  The  fact,  however,  that  in  the  quiescent  but  still  irritable 
heart  the  rhythm  may  be  reversed  by  artificially  stimulating  the 
ventricle  first  seems  to  the  author  to  speak  strongly  against  the 
dependence  of  the  sequence  upon  any  definite  arrangement  of 
neuron  complexes.  On  the  myogenic  theory  the  sequence  of  the 
heart  beat  is  accounted  for  readily  by  relatively  simple  assumptions. 
Gaskell  and  Engelmann  have  each  laid  emphasis  upon  the  facts  in 
this  connection,  and  the  application  of  the  myogenic  theory  to  the 
explanation  of  the  normal  sequence  of  contractions  forms  one  of  its 
most  attractive  features.  Gaskell  assumes*  that  the  rhythmical 
power  of  the  muscle  at  the  venous  end  is  greater  than  that  at  the 
ventricular  end,  that  is,  if  pieces  from  the  two  ends  are  examined 
separately  it  will  be  found  that  the  spontaneous  rhythm  of  the 
tissue  from  the  venous  end  is  more  rapid.  This  portion  of  the 
heart,  therefore,  beating  more  rapidly,  sets  the  rhythm  for  the 
whole  organ,  since  a  contraction  started  at  the  venous  end  will 
propagate  itself  from  chamber  to  chamber.  That  each  chamber  of 
the  heart  has  a  rhythm  of  its  own  and  that  the  rhythm  of  the  ven- 
ous end  is  the  more  rapid  and  constitutes  the  rhythm  of  the  intact 
heart  has  been  shown  in  various  ways  upon  the  hearts  of  different 
animals.  Thus,  Tigerstedt  has  devised  an  instrument,  the  atrio- 
tome,t  by  means  of  which  the  connections  between  auricle  and 
ventricle  may  be  crushed  without  hemorrhage.  Under  such  condi- 
tions the  ventricle  continues  to  beat,  but  with  a  much  slower  rhythm 
and  with  a  rhythm  entirely  independent  of  that  of  the  auricles. 

*  Gaskell,  "Journal  of  Physiology,"  4,  61,  1883;  also  vol.  ii,  p.  180,  of 
Sehafer's  "Text-book  of  Physiology,"  1900. 

t  See  "Lehrbuch  der  Physiologic  des  Kreislaufes,"  1893. 


582  CIRCULATION    OF    BLOOD    AND    LYMPH. 

The  same  result  has  been  obtained  in  a  very  striking  way  by 
Erlanger.  This  observer  arranged  a  clamp  by  means  of  which  he 
could  compress  the  auriculoventricular  bundle  connecting  auricle 
and  ventricle.  When  the  compression  is  made  the  ventricle,  after 
an  interval,  exhibits  a  slower  rhythm  and  one  entirely  independent 
of  that  of  the  auricles.  When  the  compression  is  removed  the  ven- 
tricle falls  in  again  with  auricular  rhythm.  By  variations  in  the 
pressure  upon  the  bundle  intermediate  conditions  may  be  obtained 
in  which  the  "block"  between  auricle  and  ventricle  is  only  partial, 
and  in  which,  therefore,  the  ventricular  systole  follows  regularly 
every  second  or  third  auricular  contraction.  When  the  "block"  is 
complete  the  ventricular  rhythm  ceases  to  have  any  definite  rela- 
tionship to  that  of  the  auricle,  it  beats  entirely  independently  and 
its  rate  is  slower  than  that  of  the  auricle.  It  is  interesting  to  re- 
member that  cases  of  complete  or  partial  heart  block  occur  in  man. 
In  the  condition  known  as  the  Stokes-Adams  syndrome  the  striking 
feature  in  addition  to  attacks  of  syncope  is  a  permanently  slowed 
pulse,  the  heart  beac  falling  to  30  or  20  beats  per  minute  or  lower. 
Erlanger  has  shown  that  in  such  cases  there  may  be  complete  or 
partial  heart  block.  In  the  former  condition  the  rhythm  of  the 
ventricle  is  entirely  independent  of  that  of  the  auricle  and  of  course 
much  slower.  The  ventricles  may  be  beating  at  27  per  minute  and 
the  auricles  at  90.  In  partial  block  the  ratio  between  the  ventric- 
ular and  auricular  rate  is  definite,  every  second  or  third  auricular 
beat  being  followed  by  a  ventricular  systole  (see  Fig.  237).  In  a 
number  of  these  cases  it  has  been  shown  at  autopsy  that  there  was 
a  distinct  lesion  involving  the  auriculoventricular  bundle,  but  in 
other  cases  lesions  of  this  kind  have  not  been  discoverable.* 

1      2 


Fig.  237.— Cardiogram  from  a  case  of  Stokes-Adams  disease,  showing  two  auricular  beats 
(1,  2)  to  each  ventricular  beat. — (Erlanger.)     The  time-record  marks  fifths  of  a  second. 

In  the  hearts  of  the  cold-blooded  animals  the  same  general 
results  are  readily  obtained  when  the  tissue  between  the  different 
chambers  is  compressed  or  destroyed.  In  the  frog's  heart,  for 
instance,  if  one  ties  a  ligature  (first  ligature  of  Stannius)  between 
the  sinus  venosus  and  the  auricle,  the  auricle  and  ventricle  cease 
beating  while  the  sinus  continues  pulsating  with  its  normal  rhythm. 
Later  the  auricle  and  ventricle  may  commence  beating  again,  but 

*  See  Erlanger,  "Journal  of  Experimental  Medicine,"  1905,  vii.,  1906, 
viii.,  and  "American  Journal  of  Physiology,"  1906,  xv.  and  xvi.  For  the  litera- 
ture upon  autopsies  in  cases  of  Stokes-Adams'  disease  consult  Krumbhaar, 
"Bulletin  of  the  Ayer  Clinical  Laboratory,"  Philadelphia,  No.  6,  1910,  and 
Bachmann,  "Journal  of  Exp.  Medicine,"  16,  41,  1912. 


PROPERTIES    OF    THE    HEART    MUSCLE.  583 

if  this  happens  their  rhythm  is  slower  than  that  of  the  sinus  and 
independent  of  it.  So  in  the  terrapin's  heart,  in  which  the  sequence 
of  beat  is  so  beautifully  exhibited,  if  one  ties  a  ligature  between 
auricle  and  ventricle,  or  cuts  off  the  ventricle  entirely,  the  sinus 
venosus  and  auricle  continue  beating  at  their  normal  rhythm,  while 
the  ventricle  remains  usually  entirely  quiescent.  It  would  seem  from 
these  facts  that  in  the  mammalian  heart  the  ventricle  when  dis- 
connected from  the  auricle  is  capable  of  maintaining  a  fairly  rapid 
rhythm  of  its  own.  At  the  other  extreme,  the  terrapin's  ventricle 
when  similarly  treated  shows  ,no  spontaneous  beats  at  all.  These 
and  many  other  facts  that  might  be  quoted  support  well  the  gen- 
eral view  proposed  by  Gaskell  that  the  musculature  of  the  venous 
end  of  the  heart  (sino-auricular  node)  possesses  the  greater  rhyth- 
mical power  and  starts  the  heart  beat,  and  that  the  wave  of  ex- 
citation is  propagated  to  the  auricles  and  ventricles  through  the 
muscular  tissue,  or  the  modified  muscular  tissue  composing  the 
so-called  conducting  system.  The  precise  course  of  the  wave  of 
contraction  from  auricle  to  ventricle  and  through  the  ventricle  is 
discussed  on  p.  544. 

The  Tonicity  of  the  Heart  Muscle. — In  describing  the  phys- 
iology of  skeletal  and  plain  muscle  attention  was  called  to  their 
property  of  tonicity, — that  property  by  means  of  which  they  remain 
in  a  more  or  less  permanent  although  variable  condition  of  con- 
traction. So  far  as  the  skeletal  muscles  are  concerned,  this  con- 
dition is  dependent  upon  their  connections  with  the  nervous  system. 
Cut  the  motor  nerve,  or  destroy  the  motor  center,  and  the  muscle 
loses  its  tone, — becomes  completely  relaxed.  Tonicity  or  tonic 
activity  is  therefore  characteristic  of  the  motor  nerve  centers,  and 
is  due,  no  doubt,  to  a  more  or  less  continuous  inflow  of  sensory 
impulses  into  those  centers.  The  tonus  of  the  nerve  centers  is  a 
reflex  tonus.  In  the  plain  muscle  the  condition  of  tonus  is  also 
marked.  The  blood-vessels,  the  bladder,  the  various  viscera  are 
rarely,  if  ever,  entirely  relaxed  for  any  length  of  time.  This  tonus 
is  also  dependent,  in  many  cases,  upon  a  constant  innervation 
through  the  motor  nerves,  but  after  these  latter  have  been  destroyed 
the  plain  muscle  still  shows  this  property  of  tonicity.  So  in  the 
heart  muscle  the  power  to  maintain  a  certain  degree  of  contraction, 
a  certain  state  of  muscle  tension  quite  independently  of  the  sharp 
systolic  contractions,  is  very  characteristic.  At  the  end  of  a  normal 
diastole,  for  example,  the  ventricle  is  not  entirely  relaxed,  it  retains 
a  certain  amount  of  tonicity  as  compared  with  its  condition  when 
inhibited  through  the  vagus  nerve  or  when  dead.  The  degree  of 
this  tonicity  determines,  of  course,  the  size  of  the  ventricular 
cavity  (the  diastolic  volume)  and  the  extent  of  the  charge  it  will 
take  from  the  auricles.  As  will  be  described  in  the  next  chapter 
the  tone  of  the  heart  muscle  is  dependent  in  part  upon  its  extrinsic 


584  CIRCULATION    OF    BLOOD    AND    LYMPH. 

b  l^r 

nerves,  but  it  is  more  dependent  probably  upon  the  composition 
of  the  blood.  Like  the  property  of  rhythmicity,  that  of  tonicity  is 
most  developed  at  the  venous  end  of  the  heart.  At  least  this  is  the 
case  with  the  heart  of  the  cold-blooded  animals,  upon  which 
this  property  has  been  studied  most  carefully.  The  ventricle 
of  the  terrapin,  or  strips  excised  from  the  ventricle  and  sus- 
pended so  that  their  movements  can  be  recorded,  often  vary 
greatly  in  length  with  differences  in  condition.  These  varia- 
tions are  due  to  changes  in  tone.  Not  infrequently  these 
changes  take  on  a  rhythmical  character;  so  that  if  the  ven- 
tricle is  beating  one  sees  upon  the  record  regular  tone  waves, 
an  alternate  slow  shortening  and  slow  relaxation  quite  inde- 
pendent of  the  rhythmical  beats.  The  tissue  of  the  auricle  and 
especially  of  the  sinus  venosus  exhibits  this  property  to  a  much 
more  marked  extent  (see  Fig.  238) .  The  tone — that  is,  the  length 
of  the  piece — if  in  strips,  or  the  capacity  of  the  chamber,  if  used 
entire,  is  continually  changing  and  oftentimes  in  a  rhythmical 


Fig.  238. — To  show  tone  waves  in  heart  muscle.  The  record  shows  contractions  of  > 
•trip  of  the  anus  venosus  (terrapin's  heart)  suspended  in  a  bath  of  blood-serum.  In  addi- 
tion to  the  sharp  contractions  marked  by  the  lines  there  are  longer,  wave-like  shortenings 
and  relaxations,  irregular  in  character,  which  are  due  to  variations  in  tone. 

way.  Fano*  has  made  a  special  study  of  this  property  and  has 
suggested  that  the  tone  changes  or  contractions  may  be  due  to 
the  activity  of  a  substance  in  the  heart  different  from  that  which 
mediates  the  ordinary  contractions.  Botazzif  suggests  that,  while 
the  usual  sharp  systolic  contraction  is  due  to  the  cross-striated 
(anisotropous)  substance,  the  slower  tone  changes  may  be  due 
to  the  undifferentiated  sarcoplasm.  However  this  may  be,  the 
property  of  tonicity  is  an  important  one  in  the  physiology  of  the 
heart  and  of  the  other  visceral  organs.  Through  it  a  certain  ten- 
sion of  the  musculature  is  maintained,  and  the  size  of  the  cavities 
and,  therefore,  the  output  of  the  ventricles  is  controlled.  A 
diminution  in  tonicity  constitutes  an  important  factor  in  the 
pathological  condition  known  as  acute  dilatation  of  the  heart. 

*Fano,  "Beitrage  zur  Physiologie,"  C.  Ludwig,  zu.  s.  70  Geburtstage 
gewid.,  Leipzig,  1887. 

f  "Journal  of  Physiology,"  21,  1,  1897. 


CHAPTER  XXX. 

THE  CARDIAC  NERVES  AND  THEIR  PHYSIOLOGICAL 

ACTION. 

The  heart  receives  two  sets  of  efferent  nerve  fibers  from  the 
central  nervous  system.  One  set  reaches  the  heart  through  the 
vagus  nerves,  and,  since  their  activity  slows  or  stops  the  heart 
beat,  they  are  spoken  of  as  the  inhibitory  nerve  fibers.  The  other 
set  passes  to  the  heart  by  way  of  the  sympathetic  chain,  and  since 
their  activity  accelerates  or  augments  the  heart  beat  they  are 
designated  usually  as  the  accelerator  nerve  fibers.  In  addition  the 
heart  is  provided  with  a  set  of  afferent  nerve  fibers.  Regarding 
the  functional  activity  of  these  latter  fibers,  our  experimental 
knowledge  is  limited  to  the  fact  that  some  of  them,  at  least, 
are  stimulated  at  each  beat  of  the  heart  (p.  618).  and  that 
possibly  some  of  them  help  to  form  the  so-called  depressor 
nerve  (p.  618),  Under  pathological  conditions  these  afferent 
fibers  may  produce  painful  sensations. 

The  Course  of  the  Cardiac  Fibers. — The  vagus  nerve  gives 
off  several  branches  that  supply  the  heart.  The  superior  car- 
diac branches  arise  from  the  vagus  in  the  neck  somewhere 
between  the  origins  of  the  superior  and  the  inferior  laryngeal 
nerves.  The  inferior  cardiac  branches  arise  from  the  thoracic 
portion  of  the  vagus  near  the  origin  of  the  inferior  laryngeal 
(N.  recurrens)  and,  indeed,  some  of  these  branches  may  spring 
directly  from  the  latter  nerve.  The  inhibitory  fibers  probably 
arise  in  these  inferior  branches  chiefly.  Both  superior  and 
inferior  cardiac  branches  pass  toward  the  heart  and  unite 
with  the  cardiac  branches  from  the  sympathetic  chain  to  form 
the  cardiac  plexus.  This  plexus  lies  on  the  arch  and 
ascending  portion  of  the  aorta,  and  from  it  the  heart  receives 
directly  both  its  inhibitory  and  accelerator  fibers.  The  inhibitory 
fibers  of  the  heart  form  a  part  of  the  outflow  of  bulbar  autonomic 
fibers  (p.  255)  through  the  vagus  nerve.  The  preganglionic  fibers 
probably  end  around  ganglion  cells  in  the  heart,  which  in  turn  send 
their  axons  as  postganglionic  fibers  to  the  heart  muscle. 

The  Action  of  the  Inhibitory  Fibers. — If  the  vagus  nerve 
in  the  neck  of  an  animal  is  cut  and  its  peripheral  end  is  stimulated 
the  heart  is  slowed  or  stopped  altogether  according  to  the  strength 
of  the  stimulus.  This  effect  is  illustrated  in  Figs.  239  and  240. 

585 


586 


CIRCULATION  OF  BLOOD  AND  LYMPH. 


This  inhibitory  influence  upon  the  heart  beat  was  first  described 
in  1845  by  the  two  brothers,  Edward  Weber  and  E.  H.  Weber. 
It  was  a  physiological  discovery  of  the  first  importance,  not  only 
as  regards  the  physiology  of  the  heart,  but  from  the  standpoint 
of  general  physiology,  since  it  gave  the  first  clear  instance  of  the 
possibility  of  inhibitory  action  through  nerve  fibers. 

If  the  heart  is  examined  during  its  complete  inhibition  it  will 

be  seen  that  it  stops  in  diastole, 
and  indeed  the  diastole  is  more 
complete  than  normal, — the  heart 
dilates  to  a  very  large  extent,  and 
becomes  swollen  with  blood.  This 
latter  fact  is  taken  usually  as  proof 
that  the  action  of  the  inhibitory 
fibers  not  only  prevents  the  usual 
systole,  but  also  removes  the  to- 
nicity  of  the  musculature.  Exam- 
ination of  the  heart  shows  also  that 
the  inhibition  affects  the  whole 
heart, — both  auricles  and  ventricles 
are  slowed  or  stopped,  as  the  case 
may  be.  That  the  vagus  nerve  in 
man  also  contains  inhibitory  fibers 
to  the  heart  is  made  highly  probable 
by  everything  known  concerning 
the  conditions  under  which  the  heart 
is  slowed  or  stopped  temporarily, 
and  has,  moreover,  been  demon- 
strated directly  in  several  instances 
upon  living  men.*  These  inhibitory 
fibers  have  been  shown  to  exist  in 
all  classes  of  vertebrates  and  in  a 
number  of  the  invertebrates, — a 
fact  which  in  itself  would  indicate 
the  great  importance  of  their  in- 
fluence upon  the  effective  activity  of 
the  heart.  In  the  mammals  gener- 
ally employed  in  laboratory  experi- 
ments the  inhibitory  fibers  occur  in 
both  vagi;  in  some  of  the  lower  vertebrates,  however,  especially  in 
the  terrapin,  the  inhibitory  fibers  may  be  found  exclusively  or 
mainly  in  the  right  vagus. 

*  See  especially  Thanhoffer,  "Centralblatt  f.  d.  med.  Wiss.,"  1875,  who 
gives  an  account  of  an  experiment  in  which  the  vagi  were  compressed  in  the 
neck,  with  a  resulting  stoppage  of  the  heart  and  loss  of  consciousness. 


Fig.  239.— To  show  the  inhibition 
of  the  terrapin's  heart  due  to  stimula- 
tion of  the  vagus  nerve.  The  upper 
tracing  (/)  records  the  contractions  of 
the  left  auricle ;  the  lower  (77)  the  con- 
tractions of  the  ventricle.  The  vagus 
was  stimulated  three  times,  each 
chamber  coming  to  a  complete  stop. 
On  removing  the  stimulus  it  will  be 
noted  that  the  auricular  contractions 
increase  gradually  to  their  normal, 
while  the  ventricular  contractions 
start  off  at  full  strength. 


THE    CARDIAC    NERVES. 


587 


Analysis  of  the  Action  of  the  Inhibitory  Fibers. — The  prom- 
inent effect  of  the  action  of  the  inhibitory  fibers  is  the  slowing 


Fig.  240. — To  show  the  inhibition  of  the  heart  from  stimulation  of  the  vagus  in  the 
dog.  Record  B  is  the  blood-pressure  tracing.  The  vagus  was  stimulated  twice.  The 
marks  x,  x,  indicate  the  beginning  and  end  of  the  stimulus.  The  first  stimulation  waa 
weak ;  it  will  be  noted  that  the  heart  escaped  and  began  beating  before  the  stimulus  was 
withdrawn.  The  second  stimulus  was  stronger;  the  inhibition  lasted  some  time  after  re- 
moval of  the  stimulus.  The  upper  curve  (K)  is  a  plethysmographic  (oncometer)  tracing 
of  the  volume  of  the  kidney.  It  will  be  noted  that  when  the  heart  stops  and  blood-pressure 
falls  the  kidney,  like  the  other  organs,  diminishes  in  volume.  (Dawson.) 

of  the  rate  of  the  heart  beat.  Numerous  observers  have  called 
attention  to  the  fact  that  the  vagus  fibers  may  also  cause  a  weaken- 
ing in  the  force  of  the  beat  as  well  as  a  slowing  in  the  rate,  or, 
indeed,  the  two  effects  may  be  obtained  separately.  This  fact  has 
been  shown  especially  for  the  auricles.*  In  the  heart  of  the  terrapin 
one  may,  by  using  weak  stimuli,  obtain  only  a  weakening  of  the 
auricular  beats  without  any  interference  with  the  rate  (Fig.  241), 
while  by  increasing  the  stimulus  the  slowing  in  rate  becomes  evident 
combined  with  a  diminution  in  force  or  extent.  Although  the 

*  Bayliss  and  Starling,  "Journal  of  Physiology,"  13,  410,  1892. 


588 


CIRCULATION    OF    BLOOD    AND    LYMPH. 


force  of  the  beat  may  be  influenced  without  altering  the  rate,  the 
reverse  does  not  hold.  Usually,  for  the  auricle,  at  least,  any  stimulus 
that  slows  the  beat  also  weakens  the  individual  beat.  Whether 
the  vagus  fibers  exercise  a  similar  double  influence  directly  upon 
the  ventricle  is  not  so  clear.  Some  observers  find  that  when  the 
ventricle  is  inhibited  the  beats,  although  slower,  are  stronger,  while 
others  obtain  an  opposite  result.  It  seems  probable,  as  stated 
by  Johansson  and  Tigerstedt,  that  the  result  obtained  depends 

largely  on  the  strength  of  stimulus 
used.  These  observers  found*  that 
with  relatively  weak  stimuli  the 
contractions  of  the  ventricle,  though 
slower,  are  stronger,  while  with 
stronger  stimuli  the  contractions  are 
diminished  in  strength  as  well  as 
rate.  The  question  is  complicated 
by  the  difficulty  of  separating  the 
direct  effect  of  the  vagus  on  the 
ventricle  from  the  indirect  effect 
brought  about  by  the  changes  in  the 
auricular  beat.  The  inhibitory  in- 
fluence makes  itself  felt  also  upon 
the  conductivity  of  the  heart.  This 
fact  has  been  noted  by  several  ob- 
servers. A  striking  example  is  seen 
in  the  case  of  partial  heart  block. 
When  as  the  result  of  some  injury 
or  pressure  in  the  auric ulo- ventricu- 
lar region  or  from  some  other  less 
evident  cause  there  is  a  partial  block,  so  that  the  ventricle  con- 
tracts once  to  two  or  three  beats  of  the  auricle,  vagus  stimulation 
may  be  followed  at  once,  as  an  after-effect,  by  a  return  to  the 
normal  beat,  a  re-establishment  of  a  one-to-one  rhythm.  Under 
other  circumstances  the  contrary  effect  of  vagus  stimulation 
has  been  described.  From  the  results  cited  it  seems  evident  that 
the  vagus  nerve  may  affect  the  rate  and  the  force  of  the  con- 
tractions, and  also  the  conductivity  or  the  propagation  of  the 
wave  of  excitation.  These  separate  influences  have  been  referred 
by  some  authors  to  the  existence  of  different  kinds  of  nerve  fibers, 
each  exerting  its  own  influence,  but  it  seems  preferable  to  assume, 
on  the  contrary,  that  only  one  kind  of  fiber  is  present,  and  that 
its  influence  on  the  metabolic  changes  in  the  heart  muscle  expresses 
itself  differently  upon  the  several  different  properties  of  the  tissue 
according  to  the  extent  of  its  action. 

*  See  Tigerstedt,  "  Lehrbuch  der  Physiologic  des  Kreislaufes,"  1893,  p.  247. 


Fig.  241. — To  show  the  effect  of 
vagus  stimulation  on  the  force  only  of 
the  auricular  beat  in  the  terrapin's 
heart:  A,  Record  of  the  auricular 
beats;  V,  record  of  the  ventricular 
beats.  The  vagus  was  stimulated  be- 
tween x  and  x.  It  will  be  noted  that 
the  ventricular  beats  are  not  affected, 
and  that  the  auricular  beats  diminish 
in  extent  without  any  change  in  rate. 


THE    CARDIAC    NERVES.  589 

Engelmann  has  made  an  attempt  to  analyze  the  influence  exerted  by  the 
cardiac  nerves  (inhibitory  and  accelerator).  He  designates  these  influences 
under  four  different  heads  with  the  further  supposition  that  they  are  mediated 
by  different  fibers:  (1)  The  chronotropic  influence,  affecting  the  rate  of  con- 
traction, positive  chronotropic  actions  causing  an  acceleration  and  negative 
chronotropic  actions  a  slowing  of  the  rate.  (2)  The  bathmotropic  influence, 
affecting  the  irritability  of  the  muscular  tissue;  this  also  may  be  positive  or 
negative.  (3)  The  dromotropic  influence,  positive  or  negative,  affecting  the 
conductivity  of  the  tissue.  (4)  The  inotropic  influence,  positive  or  negative, 
affecting  the  force  or  energy  of  the  contractions.* 

Does  the  Vagus  Affect  Both  Auricle  and  Ventricle? — The 
inhibitory  action  of  the  vagus  is  most  marked  upon  the  venous 
end  of  the  heart,  and  the  question  has  arisen  as  to  whether  it  affects 
the  ventricle  directly  or  not.  Gaskell  gave  evidence  to  indicate 
that  in  the  terrapin  the  auricle  only  is  inhibited,  the  ventricle  stop- 
ping because  it  fails  to  receive  its  normal  impulse  from  the 
auricle.  When  this  heart  is  inhibited  the  contractions  of  the 
auricle  after  cessation  of  inhibition  gradually  increase  in  amplitude 
until  the  normal  size  is  reached;  in  the  ventricle,  on  the  contrary, 
the  first  contraction  after  inhibition  is  of  normal  size  or  greater 
than  normal  (see  Fig.  239).  When  a  block  is  produced  in  the 
mammalian  heart  between  auricle  and  ventricle — by  clamping  the 
connecting  muscular  bundle,  for  instance — stimulation  of  the 
vagus  stops  the  auricle  only  t,  and  the  result  would  seem  to  indicate 
that  the  vagus  affects  only  the  auricle,  unless  it  is  assumed  that 
the  clamp  has  interrupted  the  inhibitory  paths  to  the  ventricle. 
On  the  other  hand,  in  favor  of  the  view  that  the  vagus  fibers  reach 
the  ventricle  and  influence  its  beats  directly,  we  have  the  fact, 
emphasized  by  Tigerstedt,  namely,  that  when  the  connection 
between  auricle  and  ventricle  is  severed  suddenly  the  ventricle 
frequently  continues  to  beat  at  its  own  rhythm  without  any  obvious 
pause.  It  would  seem  from  this  fact  that  when  the  whole  heart 
is  inhibited  by  stimulation  of  the  vagus  the  ventricle  does  not 
stop  simply  because  the  auricle  fails  to  send  on  its  usual  contraction 
wave,  since,  if  that  were  so,  cutting  off  the  auricle  or  clamping  the 
connection  between  it  and  the  ventricle  should  also  bring  on  a 
ventricular  pause,  as  happens  in  the  case  of  the  terrapin's  heart. 
It  seems,  however,  to  be  the  general  belief  of  those  who  have  experi- 
mented with  the  subject  that  the  action  of  the  vagus  is  exerted 
mainly  upon  the  auricles,  and,  indeed,  there  is  some  evidence  t  that 
its  effect  is  felt  mainly  upon  that  small  portion  of  the  auricle  (the 
sin o-auricular  node)  in  which  the  normal  heart-beat  takes  its  origin. 

Escape  from  Inhibition. — Strong  stimulation  of  the  vagus 
may  stop  the  entire  heart,  but  the  length  of  time  during  which  the 

*Englemann,  "Archiv  f.  Physiologic,"  1900,  p.  313,  and  1902,  suppl. 
volume,  p.  1. 

t  Erlanger,  "Archiv  f.  d.  ges.  Physiologic,"  127,  77,  1909. 
t  Flack,  "Journal  of  Physiology,"  41,  64,  1910. 


590  CIRCULATION    OF    BLOOD    AND    LYMPH. 

heart  may  be  maintained  in  this  condition  varies  in  different  species 
and  indeed  to  some  extent  in  different  individuals.*  In  some  ani- 
mals— cats,  for  example — the  strongest  stimulation  of  the  nerve 
serves  frequently  only  to  slow  the  heart  instead  of  causing  complete 
standstill.  In  dogs  the  heart  is  stopped  by  relatively  weak  stimu- 
lation, although  if  the  stimulation  is  maintained  the  heart,  as  a 
rule,  escapes  from  the  inhibition.  In  some  dogs  the  heart  may 
be  held  inhibited  long  enough  to  cause  the  death  of  the  animal 
unless  artificial  respiration  is  maintained,  but  usually  the  heart 
beat  soon  breaks  through  the  complete  inhibition.  The  "inner 
stimulus  "  in  such  cases  increases  in  strength  sufficiently  to  overcome 
the  opposing  inhibitory  influence,  and  this  circumstance  may  be 
regarded  as  an  argument  against  those  views  that  trace  the  origin  of 
the  "inner  stimulus"  to  some  of  the  products  formed  during  the  ca- 
tabolism  of  contraction.  Moderate  stimulation  of  the  vagus,  suffi- 
cient simply  to  slow  the  rate  of  beat,  can  be  maintained  without  dimi- 
nution in  effect  for  very  long  periods;  indeed,  as  is  explained  in  the 
next  paragraph,  the  heart  beat  is  kept  partially  inhibited  more  or 
less  continuously  through  life  by  a  constant  activity  of  the 
vagus.  In  the  cold-blooded  animals,  especially  the  terrapin, 
the  heart  may  be  kept  completely  inhibited  for  hours  by  stimu- 
lation of  the  vagus.  Mills  reports  that  he  has  kept  the  heart 
of  the  terrapin  in  this  condition  for  more  than  four  hours,  f 
Most  observers  state  that  complete  .inhibition  can  be  maintained 
for  a  longer  time  when  the  stimulus  is  applied  alternately  to 
the  two  vagi,  but  it  is  possible  that  this  result  is  due  to  the  fact 
that  continuous  stimulation  applied  to  a  nerve  usually  results 
in  some  local  loss  of  irritability. 

Reflex  Inhibition  of  the  Heart  Beat — Cardio-inhibitory 
Center. — The  inhibitory  fibers  may  be  stimulated  reflexly  by  action 
upon  various  sensory  nerves  or  surfaces.  One  of  the  first  experi- 
mental proofs  of  this  fact  was  furnished  by  Goltz's  often-quoted 
"Klopfversuch."J  In  this  experiment,  made  upon  frogs,  the  ob- 
server obtained  standstill  of  the  heart  by  light,  rapid  taps  on  the 
abdomen,  and  the  effect  upon  the  heart  failed  to  appear  when  the 
vagi  were  cut.  In  the  mammals  every  laboratory  worker  has  had 
numerous  opportunities  to  observe  that  stimulation  of  the  central 
stumps  of  sensory  nerves  may  cause  a  reflex  slowing  of  the  heart 
beat.  The  effect  is  usually  very  marked  when  the  central  stump 
of  one  vagus  is  stimulated,  the  other  vagus  being  intact.  The 
vagus  carries  afferent  fibers  from  the  thoracic  and  abdominal 
viscera,  and  most  observers  state  that  the  heart  may  be  reflexly 
inhibited  most  readily  by  simulation  of  the  surfaces  of  the  ab- 

*  See  Hough,  "Journal  of  Physiology,"  18,  161,  1895. 
t"  Journal  of  Physiology,"  6,  246. 
|  }  Goltz,  "Virchow's  Archiv  f.  pathol.  Anatomic,  etc.,"  26,  11,  1863. 


THE    CARDIAC    NERVES.  591 

dominal  viscera,  by  a  blow  upon  the  viscera,  for  example,  or 
by  sudden  distention  of  the  stomach.  In  man  similar  results 
are  noticed  very  frequently.  Acute  dyspepsia,  inflammation  of 
the  peritoneum,  painful  stimulation  of  sensory  surfaces, — the 
testes,  for  instance,  or  the  middle  ear, — may  cause  a  marked  slowing 
of  the  heart, — a  condition  designated  as  bradycardia.  What 
takes  place  in  all  such  cases  is  that  the  afferent  impulses  carried 
into  the  central  nervous  system  reflexly  stimulate  the  nerve  cells 
in  the  medulla  which  give  origin  to  the  inhibitory  fibers.  These 
cells  form  a  part  of  the  great*  motor  nucleus  (N.  ambiguus)  from 
which  arise  the  motor  fibers  of  the  vagus  and  the  glossopharyngeus. 
The  particular  group  of  cells  from  which  the  inhibitory  fibers  to  the 
heart  originate  has  not  been  delimited  anatomically.  Efforts  have 
been  made  to  locate  them  by  vivisection  experiments,  but  this 
method  has  shown  no  more  perhaps  than  that  they  are  found  in  the 
region  of  origin  of  the  vagus  nerve.  Physiologically,  however,  this 
group  of  cells  forms  a  center  which  is  of  the  greatest  importance  in 
controlling  the  activity  of  the  heart.  It  is  designated,  therefore,  as 
the  cardio-inhibitory  center.  We  may  define  the  cardio-inhibitory 
center  as  a  bilateral  group  of  cells  lying  in  the  medulla  at  the  level  of 
the  nucleus  of  the  vagus  and  giving  rise  to  the  inhibitory  fibers 
of  the  heart.  The  two  sides  are  probably  connected  by  commis- 
sural  cells  or  else  each  nucleus  sends  fibers  to  the  vagus  of  each 
side.  Through  this  center  all  reflexes  that  affect  the  heart  by  way  of 
the  inhibitory  fibers  must  take  place.  These  reflexes  may  be  occa- 
sioned by  incoming  sensory  impulses  through  the  spinal  or  cranial 
nerves,  or  by  impulses  coming  down  from  the  higher  portions  of 
the  brain.  The  center  may  also  be  stimulated  directly,  either  by 
pressure  upon  the  medulla,  which  may  give  rise  to  slow  heart  beats 
or,  as  they  are  sometimes  called,  vagal  beats,  or  by  changes  in  the 
composition  of  the  blood.  With  regard  to  the  reflex  stimulation  of 
this  center  it  is  important  to  bear  in  mind  the  general  physiological 
rule  that  afferent  impulses  may  either  excite  or  inhibit  the  activity 
of  nerve  centers.  In  the  former  case  the  heart  rate  would  be 
slowed,  in  the  latter  case  it  would  be  quickened  if  the  center  were 
previously  in  a  state  of  activity. 

The  Tonic  Activity  of  the  Cardio-inhibitory  Center.— The 
cells  of  the  cardio-inhibitory  center  are  in  constant  activity  to  a 
greater  or  less  extent.  As  a  consequence,  the  heart  beat  is  kept  con- 
tinually at  a  slower  rate  than  it  would  normally  assume  if  the 
inhibitory  apparatus  did  not  exist.  This  tonic  activity  of  the  vagus 
is  beautifully  exhibited  by  simple  section  of  the  two  vagi,  or  by  inter- 
rupting, in  some  other  way — cooling,  for  example — the  connection 
between  the  center  and  the  heart.  When  the  two  vagi  are  cut  the 
heart  rate  increases  greatly  and  the  blood-pressure  rises  on  account 
of  the  greater  output  of  blood  in  a  unit  of  time  (Fig.  242) .  Section 


592  CIRCULATION    OF    BLOOD    AND    LYMPH. 

of  one  vagus  gives  usually  a  partial  effect, — that  is,  the  heart-rate 
is  increased  somewhat, — but  it  is  still  further  increased  by  section 
of  the  second  vagus.  The  exact  result  obtained  when  the  nerves  are 


Fig.  242. — To  show  the  effect  of  section  of  the  two  vagi  in  the  dog  upon  the  rate  of 
heart  beat  and  the  blood-pressure:  1  marks  the  section  of  the  vagus  on  the  right  side; 
2,  section  of  the  second  vagus.  The  numerals  on  the  vertical  mark  the  blood-pressures ; 
the  numerals  on  the  blood-pressure  record  give  the  rate  of  heart  beats.  (Dawson.) 

severed  separately  varies  undoubtedly  with  the  conditions, — for 
instance,  with  the  intensity  of  the  tonic  activity  of  the  center. 
Throughout  life,  speaking  in  general  terms,  the  cardio-inhibitory 
center  keeps  the  "brakes"  on  the  heart  rate,  and  the  extent  of  its 
action  varies  under  different  conditions.  When  its  tonic  action  is 
increased  the  rate  becomes  slower;  when  it  is  decreased  the  rate 
becomes  faster.  In  all  probability,  this  tonic  action  of  the  center, 
like  that  of  the  motor  centers  generally,  is  in  reality  a  reflex  tonus. 
That  is,  it  is  not  due  to  automatic  processes  generated  within  the 
nerve  cells  by  their  own  metabolism  or  by  changes  in  their 
liquid  environment,  but  to  stimulations  received  through  sensory 
nerves.  The  continuous  though  varying  inflow  of  impulses  into 
the  central  nervous  system  through  different  nerve  paths  keeps 
the  center  in  that  state  of  permanent  gentle  activity  which  we 


THE    CARDIAC    NERVES.  593 

designate  as  "tone."  It  is  possible,  of  course,  that  certain 
afferent  paths  may  be  in  specially  close  functional  relationship 
to  the  center,  and  the  fact  that  at  each  heart  beat  its  own 
sensory  fibers  are  stimulated  (p.  618,  Fig.  280)  would  suggest 
that  these  fibers  may  have  this  function. 

The  Action  of  Drugs  on  the  Inhibitory  Apparatus. — The 
existence  of  the  inhibitory  fibers  to  the  heart  furnishes  a  means 
of  explaining  the  cardiac  action  of  a  number  of  drugs, — atropin, 
muscarin  or  pilocarpin,  nicotin,  curare,  digitalis,  etc., — for  the 
details  of  which  reference  must  be  made  to  works  on  pharmacology.* 
The  action  of  the  first  three  named  illustrates  especially  well  the 
application  that  has  been  made  of  physiology  in  modern  pharma- 
cology. Atropin  administered  to  those  animals,  such  as  the  dog 
or  man,  in  which  the  inhibitory  fibers  of  the  vagus  are  in  constant 
activity,  causes  a  quickening  of  the  heart  rate.  Indeed,  the  heart 
beats  as  rapidly  as  if  both  vagi  were  cut.  After  the  use  of  atropin, 
moreover,  stimulation  of  the  vagus  nerve  fails  to  produce  inhibition. 
The  action  of  atropin  is  satisfactorily  explained  by  assuming  that 
it  paralyzes  the  endings  of  the  (postganglionic)  inhibitory  fibers 
in  the  heart  muscle,  just  as  curare  paralyzes  the  terminations  of 
the  motor  fibers  in  skeletal  muscle.  Atropin  exercises  a  similar 
effect  upon  the  nerve  terminations  in  the  intrinsic  muscles  of  the 
eyeball  and  in  many  of  the  glands.  On  the  contrary,  when  mus- 
carin or  pilocarpin  is  administered  it  causes  a  slowing  and  finally 
a  cessation  of  the  heart  beat.  Since  this  effect  may  be  removed 
by  the  subsequent  use  of  atropin  it  is  assumed  that  the  two  former 
drugs  excite  or  stimulate  the  endings  of  the  inhibitory  fibers  in 
the  heart  and  thus  bring  the  organ  to  rest  in  diastole,  as  happens 
after  electrical  stimulation  of  the  vagus  nerve.  Some  authors, 
however,  believe  that  these  drugs  do  not  act  upon  the  terminals 
of  the  vagus  fibers,  but  upon  the  muscular  tissue  itself  or  upon  a 
specialized  "  receptive  substance "  (Langley)  contained  in  the 
muscle.  A  final  statement  cannot  be  made  upon  this  point,  but 
the  current  belief  is  that  the  atropin  paralyzes  while  the  muscarin 
or  pilocarpin  stimulates  the  endings  of  the  inhibitory  fibers  in  the 
substance  of  the  heart. 

The  Nature  of  Inhibition. — Since  the  discovery  of  the  inhibi- 
tory nerves  of  the  heart  furnished  the  first  conclusive  proof  of  the 
existence  in  the  body  of  definite  nerve  fibers  with  apparently  the 
sole  function  of  inhibition,  it  seems  appropriate  in  this  connection 
to  refer  to  the  views  regarding  the  nature  of  this  process.  Several 
general  views  of  the  nature  of  inhibition  have  been  proposed,  but 
the  one  that  is  most  definite  and  has  met  with  most  favor  is  that 

*  Consult  Cushny,  "Text-book  of  Pharmacology  and  Therapeutics,"  Phila- 
delphia. 


594  CIRCULATION    OF    BLOOD    AND    LYMPH. 

suggested  by  Gaskell.*  This  author  has  shown  that  the  after-effects 
of  stimulation  of  the  inhibitory  fibers  are  beneficial  rather  than  in- 
jurious to  the  heart ;  that  is,  under  certain  circumstances  an  improve- 
ment may  be  noticed  in  the  rate  or  force  of  the  beat  or  in  the  con- 
ductivity. He  has  also  shown,  by  an  interesting  experiment,  that 
during  the  state  of  inhibition  the  heart  tissue  is  made  increasingly 
electropositive  in  comparison  with  a  dead  portion  of  the  tissue. 
To  show  this  fact  the  tip  of  the  auricle  was  killed  by  heat  and  this  spot 
(a)  and  a  point  at  the  base  of  the  auricle  (6)  were  connected  with  a 
galvanometer.  Under  such  conditions  a  strong  demarcation  cur- 
rent was  obtained  flowing  through  the  galvanometer  from  b  to  a. 
If  the  auricle  contracted  a  negative  variation  resulted,  since  during 
activity  6  became  less  positive  as  regards  a.  If,  on  the  contrary, 
the  auricle  was  inhibited  by  stimulation  of  the  inhibitory  fibers 
a  positive  variation  was  obtained;  b  became  more  positive 
toward  a.  On  the  basis  of  such  results  Gaskell  concludes  that 
inhibition  in  the  heart  is  due  to  a  set  of  metabolic  changes  of  an 
opposite  character  to  those  occurring  during  contraction.  In  the 
latter  condition  the  metabolism  is  catabolic,  and  consists  in  the 
breaking  down  of  complex  substances  into  simpler  ones  with  the 
liberation  of  energy  as  heat  and  work.  During  inhibition,  on  the 
contrary,  the  processes  are  anabolic  or  synthetic  and  result  in  the 
formation  of  increased  contractile  material  whereby  the  condition 
of  the  heart  is  improved.  He  would  regard  the  inhibitory  fibers, 
therefore,  as  the  anabolic  nerve  of  the  heart  and  their  constant 
action  throughout  life  as  an  aid  to  the  nutrition  of  the  heart.  The 
same  general  view  may  be  extended  to  all  cases  of  inhibition,  and 
Gaskell  believes  that  all  muscular  tissues  are  supplied  with  anabolic 
(inhibitory)  and  catabolic  (motor)  fibers,  f 

A  more  specific  theory  applicable  to  the  case  of  the  heart  has  been  proposed 
by  the  author.  J  In  experiments  made  upon  the  isolated  heart  of  the  dog  it 
has  been  shown  that  during  stimulation  of  the  vagus  potassium  in  diffusible 
form  is  given  off  from  the  heart  muscle  (auricles).  It  is  known  that  potassium 
salts  in  a  certain  concentration  in  the  circulating  liquid  will  bring  the  heart 
to  a  stand-still,  and  the  state  of  potassium  inhibition  thus  produced  resembles 
very  closely  the  state  of  vagus  inhibition.  Since  the  vagus  when  stimulated 
liberates  potassium  in  a  diffusible  form,  it  is  suggested  that  its  action  in 
stopping  the  heart  is  effected  through  the  agency  of  this  substance.  The 
potassium  exists  in  large  percentage  in  the  heart-muscle,  but  in  a  combined 
form,  and  the  theory  assumes  that  the  vagus  impulses  initiate  a  dissociation 
or  cleavage  of  some  sort  which  sets  free  some  potassium  in  soluble  form.  If 
it  is  assumed  that  this  liberation  takes  place  in  the  part  of  the  heart  in  which 

*  Gaskell,  "Philosophical  Transactions  of  the  Royal  Society,"  London; 
Croonian  Lecture,  part  in,  1882;  "Journal  of  Physiology,"  7,  46;  and  Meek 
and  Eyster,  "American  Journal  of  Physiology,"  30,  271,  1912. 

f  For  a  general  discussion  of  this  idea  and  of  the  importance  of  inhibitory 
actions,  see  Melzer,  "Inhibition,"  "New  York  Medical  Journal,"  May  13, 
20,  27,  1899. 

t  Howell  and  Duke,  "American  Journal  of  Physiology,"  21,  51,  1908. 


THE    CARDIAC    NERVES. 


595 


the  beat  originates,  the  theory  offers  a  simple  explanation  of  the  stoppage  of 
the  beat,  of  the  quick  recovery  after  stimulation  ceases,  and  of  the  retention 
af  irritability  to  direct  stimula- 
tion shown  by  the  heart  during 
vagus  inhibition.  A  heart  that 
has  been  stopped  by  an  excess 
of  potassium  chloride  added  to 
the  circulating  liquid  beats  very 
promptly  as  soon  as  the  excess 
of  the  potassium  is  removed,  and 
as  in  the  case  of  vagus  inhibition 
it  seems  often  to  show  a  notice- 
able improvement  in  condition. 

That  the  inhibitory  ef- 
fect of  the  vagus  im- 
pulses upon  the  heart  is 
not  due  to  any  peculiarity 
in  properties  of  these 
fibers  or  of  the  impulses 
themselves,  but  is  depend- 
ent rather  upon  the  place 
or  manner  of  ending  in  the 
heart,  has  been  demon- 
strated by  direct  experi- 
ment. Erlanger*  has  shown 
that  when  an  ordinary 
spinal  nerve  (fifth  cervical) 
is  sutured  to  the  peripheral 
end  of  the  cut  vagus,  it  will, 

^t*^   +'~     t  Fig.  243.— Schematic  representation  of  the 

alter  time  tor  regeneration         course  of  the  accelerator^  fibers^to  the  dog[s  heart 

has  been  allowed,  cause, 
when  stimulated,  the  usual 
stoppage  of  the  heart. 

The  Course  of  the  Ac- 
celerator Fibers. — The 
heart  receives  efferent  or 
motor  nerve  fibers  from 
the  sympathetic  system  in 
addition  to  those  reaching  it  by  way  of  the  vagus  nerve.  Atten- 
tion was  first  called  to  these  sympathetic  fibers  by  Legallois 
(1812),  but  our  recent  knowledge  dates  from  the  experiments 
made  by  von  Bezold  (1862),  which  were  afterward  completed 
by  the  Cyon  brothers— M.  and  E.  Cyon  t— 1866.  These  fibers 
when  stimulated  cause  an  increased  rate  of  beat  and  are,  there- 
fore, designated  as  the  accelerator  nerve  of  the  heart.  Their 

*  Erlanger,  "American  Journal  of  Physiology,"  13,  372,  1905. 

t  For  the  history  and  literature  of  the  accelerator  nerves,  see  Cyon,  article 
"Cceur,"  p.  103,  in  Richet's  " Dictionnaire  de  Physiologic,"  lonn'  ™  TJ-*"- 
stedt,  "Lehrbuch  der  Physiologic  des  Kreislaufes,"  260,  1893. 


JIT 
W 


— right  side. — (Modified  from  Pawlow.)  1  he  sym- 
pathetic nerve  is  represented  in  solid  black.  The 
course  of  the  accelerator  fibers  is  indicated  by  ar- 
rows. /,  Cervical  sympathetic  combined  in  neck 
with,  10,  the  vagus;  //,  ///,  IV,  rami  communi- 
cantes  from  the  second,  third,  and  fourth  thoracic 
spinal  nerves,  carrying  most  of  the  accelerator  fi- 
bers to  the  sympathetic  chain ;  7,  annulus  of  Vieus- 
sens;  8,  inferior  cervical  ganglion;  2,  3,  4,  5, 
branches  from  vagus  and  vago-sym pathetic  trunk 
going  to  cardiac  plexus  (some  of  these — 3,  5, — 
carry  accelerator  fibers;  9,  the  inferior  laryngeal 
nerve. 


1900;  or  Tiger- 


596 


CIRCULATION    OF    BLOOD    AND    LYMPH. 


course  has  been  worked  out  physiologically  in  a  number  of 
animals.  Among  the  mammalia  and,  indeed,  among  different 
animals  of  the  same  species  there  is  some  variation,  but  a  general 
conception  of  their  origin  and  course  may  be  obtained  from 
Figs.  243  and  244,  which  represent  in  a  schematic  way  the 
anatomical  path  taken  by  these  fibers.  They  emerge  from  the 
spinal  cord  in  the  anterior  roots  of  the  second,  third,  and  fourth 

thoracic  spinal  nerves.  Accord- 
ing to  some  authors  they  may 
be  found  also  in  the  fifth  tho- 
racic, the  first  thoracic,  or  even 
the  lower  cervical  spinal  nerves. 
They  pass  then  by  way  of  the 
white  rami  to  the  stellate  or 
first  thoracic  ganglion  (6),  and 
thence  by  way  of  the  annulus 
of  Vieussens  (ansa  subclavia)  (7) 
to  the  inferior  cervical  ganglion. 
A  number  of  branches  leave 
the  sympathetic  system  and  the 
vagus  in  this  region  to  pass  to 
the  cardiac  plexus  and  thence 
to  the  heart.  The  accelerator 
fibers  are  found  in  some  of  these 
branches,  mixed  in  some  cases 
with  inhibitory  fibers  from  the 
vagus.  In  the  cat  Boehm  has 
described  a  special  branch  (ner- 
vus  accelerans)  which  runs  from 
the  stellate  ganglion  directly  to 
the  cardiac  plexus  (Fig.  244). 

The  preganglionic  portion  of  some  of  the  accelerator  fibers  ends 
around  the  ganglion  cells  in  the  first  thoracic  ganglion,  while 
Others  apparently  make  their  first  termination  in  the  inferior 
cervical  ganglion.  The  accelerator  fibers  may  be  stimulated  in 
the  spinal  roots  in  which  they  emerge  (II,  III,  IV),  in  the  annulus, 
or  in  some  of  the  branches  that  arise  from  the  annulus  or  from 
the  inferior  cervical  ganglion  (5,  3,  2).  It  will  be  borne  in  mind 
that  no  accelerator  fibers  are  found  in  the  cervical  sympathetic 
above  the  inferior  cervical  ganglion. 

At  various  times  investigators  have  asserted  that  accelerator  fibers  are 
contained  also  in  the  vagus  nerve.  Thus,  it  has  been  shown  that,  after  the 
paralysis  of  the  inhibitory  fibers  in  the  heart  by  atropin,  stimulation  of  the 
vagus  causes  an  acceleration  of  the  heart.  Little  attention  has  been  paid  to 
the  physiology  of  these  fibers,  since  it  seems  evident  that  the  great  outflow  of 
accelerators  is  made  via  the  sympathetic  system. 


Fig.  244.— Sketch  to  show  the  accel- 
erator (and  augmentor)  branches  from  the 
stellate  ganglion  (in  the  cat,  left  side):  1, 
The  ventral  branch  of  the  annulus  (ansa 
subclavia);  2,  small  branch  not  constantly 
present;  3,  Boehm's  accelerator  nerve 
(N.  cardiacus  e  ganglio  stellato). 


THE    CARDIAC    NERVES.  597 

The  Action  of  the  Accelerator  Fibers. — In  experimental 
work  the  accelerators  are  usually  stimulated  in  one  or  more  of  the 
branches  represented  schematically  as  5,  3,  6,  in  Fig.  243,  or  3,  in 
Fig.  244,  The  effect  is  an  increase  in  the  rate  of  beat  of  the  heart, 
which  may  be  very  evident,  amounting  to  as  much  as  70  per  cent, 
or  more  of  the  original  rate,  or  may  be  very  slight.  When  accelera- 
tion  is  obtained  the  latent  period  is  considerable  and  the  heart 
does  not  return  at  once  to  its  normal  rate  upon  cessation  of  the 
stimulus  (see  Figs.  245  and  246).  In  some  cases  the  effect  upon  the 
heart  is  an  acceleration  pure  and  simple, — that  is,  the  rate  of  beat  is 


Fig.  245. — To  show  the  acceleration  of  the  heart-rate  in  dog  upon  stimulation  of  the 
accelerator  fibers.  The  uppermost  line  gives  the  heart-rate  as  recorded  by  a  Hurthle  manometer 
inserted  into  the  carotid;  the  middle  line  indicates  the  beginning  and  duration  of  the  stimulus 
(tetanizing  induction  shocks) ;  the  bottom  line  marks  seconds.  The  pulse-rate  was  increased 
from  105  to  135  per  minute.  The  heart  did  not  recover  its  normal  rate  until  thirty  seconds 
after  the  stimulation. 

increased  without  any  evidence  of  an  increase  in  the  force  of  the 
beats.  The  larger  number  of  beats  is  offset  by  the  smaller  amplitude, 
of  each  beat;  so  that  the  blood-pressure  in  the  arteries  is  unchanged. 
In  other  cases  the  effect  upon  the  heart  may  be  an  increase  not  only 
in  rate  but  also  in  the  force  or  amplitude  of  the  beats,  or  the  rate 
may  remain  unaffected  and  only  the  amplitude  of  the  heart 
beats  be  increased.  For  these  reasons  most  authors  favor  the 
view  that  the  accelerator  nerves,  so  called,  contain  in  reality 
two  sets  of  fibers,  one,  the  accelerators  proper,  whose  function 
is  simply  to  accelerate  the  rate,  and  one,  the  augmentors,  that 
cause  a  more  forcible  beat.  The  augmenting  action  is  obtained 
especially  from  the  nerves  of  the  left  side. 

Tonicity  of  the  Accelerators  and  Reflex  Acceleration.— 
The  results  of  the  most  careful  work  show,  without  doubt,  that  the 
accelerators  to  the  heart  are  normally  in  a  state  of  tonic  activity.* 

*  For  a  discussion  of  this  and  other  points  in  the  physiology  of  the  ac- 
celerators see  Hunt,  "American  Journal  of  Physiology,"  2,  395,  1899,  and 
"Journal  of  Experimental  Medicine,"  2,  151,  1897. 


598  CIRCULATION   OF    BLOOD    AND    LYMPH. 

When  these  nerves  are  cut  upon  both  sides  the  heart  rate  is  decreased. 
We  must  believe,  therefore,  that  under  normal  conditions  the  heart 
muscle  is  under  the  constant  control  of  two  antagonistic  influ- 
ences, one  through  the  inhibitory  fibers  tending  to  slow  the  rate, 
one  through  the  accelerator  fibers  tending  to  quicken  the  rate.  The 
actual  rate  at  any  moment  is  the  resultant  of  these  two  influences. 
While  such  an  arrangement  seems  at  first  sight  to  be  unnecessary 
from  a  mechanical  standpoint,  it  is  doubtless  true  that  it  possesses 
some  distinct  advantage.  Possibly  it  makes  the  heart  more 
promptly  responsive  to  reflex  regulation.  Balanced  mechanisms 
of  this  kind  are  found  in  other  parts  of  the  body  where  smooth  and 
prompt  reactions  to  stimulation  seem  to  be  especially  necessary, — • 
for  example,  the  constrictor  and  dilator  fibers  of  the  iris,  the  ex- 
tensor and  flexor  muscles  of  the  joints,  etc.  Physiologists  have 
studied  experimentally  the  effect  upon  the  heart  of  stimulating 
simultaneously  the  inhibitory  and  the  accelerator  nerves.  The 
work  done  upon  this  subject  by  Hunt  seems  to  make  it  very 
certain  that  in  all  such  cases  the  result,  so  far  as  the  rate  is 
concerned,  is  the  algebraic  sum  of  the  effects  of  the  separate 
stimulations  of  the  nerve.  The  inhibitory  and  the  accelerator 
fibers  must  be  considered,  therefore,  as  true  antagonists,  acting 
in  opposite  ways  upon  the  heart.  The  existence  of  the  accel- 
erator nerves  makes  possible,  of  course,  their  reflex  stimulation. 
Experimentally  it  is  found  that  stimulation  of  various  sensory 
nerves — those  of  the  limbs  or  trunk,  for  instance — may  cause 
reflexly  either  an  increase  or  decrease  in  the  heart  rate,  and  as 
a  matter  of  experience  we  know  that  our  heart  rate  may  be 
increased  by  various  changes,  particularly  by  emotional  states. 
The  natural  explanation  of  such  accelerations  is  that  they  are 


Fig.  246. — To  show  the  acceleration  and  augmentation  produced  by  a  strong  stimulus. 
Isolated  cat's  heart,  stimulation  on  left  side.  The  upper  curve  gives  the  ventricular 
contractions,  the  lower  one  the  auricular  contractions.  The  lowermost  line  gives  the 
time  in  seconds  and  the  line  above  indicates  the  duration  of  the  stimulation  of  the  accel- 
erator nerve. 

due  to  reflex  stimulation  of  the  nerve  cells  in  the  central  nervous 
system  which  give  rise  to  the  accelerator  fibers.  But  another 
point  of  view  is  possible.  An  increase  in  heart  rate  may  be 
brought  about  either  by  a  reflex  stimulation  of  the  accelerator 


THE    CARDIAC   NERVES.  599 

fibers  or  by  a  reflex  inhibition  of  the  cardio-inhibitory  center. 
Hunt  especially  has  presented  many  experimental  facts  which 
indicate  that  an  increase  in  heart  rate  from  reflex  action  may  be 
produced  by  an  inhibition  of  the  tonic  activity  of  the  cardio- 
inhibitory  center.  He  finds,  for  instance,  that  when  the  two 
vagi  are  cut  stimulation  of  various  sensory  nerves  fails  to  give 
any  increase  in  the  already  rapid  heart  rate,  while,  on  the  con- 
trary, when  the  two  accelerator  paths  are  cut  a  reflex  increase  in 
heart  rate  may  be  obtained  readily.  The  negative  result  after 
previous  section  of  the  vagi 'may  well  be  due,  however,  to  the 
fact  that  the  heart  is  then  beating  at  a  very  rapid  rate,  too 
rapid  for  the  production  of  an  additional  acceleration  through 
the  ordinary  physiological  mechanism.  Acting  on  this  view, 
Hooker*  has  shown  that  if  the  heart  is  kept  slowed  by  artificial 
stimulation  of  the  peripheral  end  of  the  vagi,  then  various 
sensory  stimuli  will  provoke  a  reflex  acceleration  which  can 
only  occur  through  the  accelerator  center.  We  may  conclude, 
therefore,  that  the  accelerator  and  the  inhibitory  fibers  are  work- 
ing constantly  on  the  heart,  and  that  its  rate  is  the  resultant  or 
algebraic  sum  of  their  effects,  and  that  sudden  changes  in  this 
rate,  such  as  follow  from  sensory  or  psychical  disturbances  of  any 
kind,  may  be  referred  to  a  reflex  effect  upon  either  the  cardio- 
inhibitory  or  the  accelerator  center.  While  physiology  has  demon- 
strated the  general  properties  of  the  regulating  nerves  of  the  heart, 
the  inhibitory,  on  the  one  hand,  and  the  accelerator  and  augmen- 
tor  on  the  other,  it  is  necessary  for  much  more  work  to  be  done  in 
order  to  explain  satisfactorily  how  these  nerves  participate  in  the 
various  normal  and  pathological  changes  of  rate  and  force  of  beat. 

The  Accelerator  Center. — The  accelerator  fibers  arise  primarily  in 
the  central  nervous  system.  Since  stimulation  of  the  upper  cervical  region 
of  the  cord  causes  acceleration,  it  seems  evident  that  the  path  must  begin 
somewhere  in  the  brain.  It  has  been  assumed  that,  like  the  inhibitory  fibers, 
the  path  starts  in  the  medulla,  and  that,  therefore,  the  cells  in  that  organ 
which  give  rise  to  the  accelerator  fibers  constitute  the  accelerator  center 
through  which  reflex  effects,  if  any,  take  place.  As  a  matter  of  fact,  the 
location  of  these  cells  of  origin  has  not  been  made  out  satisfactorily.  The 
matter  offers  unusual  difficulty  on  the  experimental  side,  owing  to  the  existence 
of  the  cardio-inhibitory  center  in  the  medulla  and  the  absence  of  any  entirely 
satisfactory  method  of  distinguishing  certainly  between  reflex  acceleration 
through  this  center  and  through  the  accelerator  center. 

*  Hooker,  "American  Journal  of  Physiology,"  19,  417,  1907. 


CHAPTER  XXXI. 

THE  RATE  OF  THE  HEART  BEAT  AND  ITS  VARIA- 
TIONS UNDER  NORMAL  CONDITIONS, 

The  rate  of  heart  beat  changes  quickly  in  response  to  variations 
in  either  the  internal  or  external  conditions.  Therein  lies,  in  fact, 
the  great  value  of  the  regulatory  (inhibitory  and  accelerator)  nerves. 
Through  their  agency,  in  large  part,  the  pump  of  the  circulation  is 
reflexly  adjusted  to  suit  the  changing  needs  of  the  organism  and 
adapted  more  or  less  successfully  to  alterations  in  the  external 
environment.  The  variations  in  the  rate  of  beat  may  be  considered 
under  three  general  heads:  (I)  Fixed  adjustments  to  the  different 
mechanical  conditions  of  the  circulation.  (II)  Variations  caused 
by  reflex  effects  upon  the  inhibitory  or  accelerator  nerves.  (Ill) 
Variations  caused  by  changes  in  the  physical  or  chemical  conditions 
of  the  blood. 

The  Fixed  Adjustments  of  Rate. — When  we  speak  of  the 
normal  pulse  rate  we  mean  the  rate  in  an  adult  when  in  a  condition 
of  mental  and  bodily  repose.  Examination  shows  that  under  these 
circumstances  there  are  great  individual  variations.  The  average 
normal  rate  for  man  may  be  estimated  at  70  beats  per  minute; 
for  woman,  78  to  80  beats;  but  the  normal  rate  for  some  individuals 
may  be  much  lower  (50)  or  much  higher  (90).  Among  the  condi- 
tions for  which  the  heart  rate  shows  a  certain  constant  fixed  adapta- 
tion the  following  may  be  mentioned : 

Variations  with  Sex. — The  average  pulse  rate  in  women  is,  as 
a  rule,  higher  than  that  in  men,  and  this  difference  seems  to  hold 
for  alfperiods  of  life. 

Variations  with  Size. — Tall  individuals  have  a  slower  pulse 
rate  than  short  persons  of  the  same  age.  Several  observers  have 
thought  that  they  could  detect  a  constant  relationship  between 
size  and  pulse  rate.  Thus,  Volkmann  believed  that  the  pulse 
rate  varies  inversely  as  the  five-ninth  power  of  the  height.  In 
the  same  direction  it  is  found  that  small  animals,  as  a  rule,  have 
a  higher  pulse  rate  than  larger  ones.  Thus,  elephant,  25-28; 
horse  and  ox,  36-50;  sheep,  60-80;  dog,  100-120;  rabbit,  150; 
mice,  700.  The  smaller  the  animal,  speaking  generally,  the  more 
rapid  is  the  consumption  of  oxygen  in  its  tissues,  and  the  increased 
demand  for  oxygen  is  met  by  an  acceleration  of  the  flow,  due  to 
the  quicker  beat  of  the  heart.  According  to  Buchanan*  the  heart 
of  the  canary  beats  at  the  extraordinary  rate  of  1000  per  minute. 
*  Buchanan,  "Science  Progress,"  July,  1910. 
600 


THE    RATE    OF    THE    HEART    BEAT  601 

Variations  with  Age. — In  line  with  the  last  condition  it  is  found 
in  man  that  the  pulse  rate  is  highest  in  infancy,  sinks  quite  rapidly 
at  first  and  then  more  slowly  up  to  adult  life,  and  rises  again 
slightly  in  very  old  age  at  the  time  that  the  body  undergoes  a 
perceptible  shrinkage.  The  most  extensive  data  upon  this  point 
are  found  in  the  works  of  the  older  observers.*  According  to  Guy, 
a  condensed  summary  of  the  average  results  obtained  at  different 
periods  of  life,  both  sexes  included,  may  be  given  as  follows: 

At  birth v 140 

Infancy 120 

Childhood 100 

Youth 90 

Adult  age 75 

Oldage 70 

Extreme  age 75-80 

The  Variations  in  Pulse  Rate  Effected  through  the  In- 
hibitory and  Accelerator  Nerves. — Most  of  the  sudden  adaptive 
changes  of  the  heart  rate  come  under  this  head.  In  the  laboratory 
we  find  that  stimulation  of  all  sensory  nerve  trunks  may  affect 
the  heart  rate,  in  some  cases  increasing  it,  in  others  the  reverse. 
In  life  we  find  that  the  pulse  rate  is  very  responsive  to  our  changing 
sensations  and  especially  to  mental  conditions  that  indicate  deep 
interest  or  emotional  excitement.  In  a  previous  paragraph  (p.  599) 
the  physiological  cause  of  this  effect  has  been  discussed  briefly.  It 
may  arise  either  from  a  reflex  excitation  of  the  accelerator  nerves 
or  a  reflex  inhibition  of  the  tonic  activity  of  the  inhibitory  nerves. 
The  facts  at  present  seem  to  indicate  that  both  mechanisms  are  used. 
In  addition  to  these  reflexes  associated  with  conscious  states  the 
heart  is  susceptible  to  reflex  influences  of  a  totally  unconscious  char- 
acter connected  with  the  states  of  activity  of  the  visceral  organs. 
For  example,  after  meals  the  heart-beat  increases  usually  in  rate 
and  especially  in  force  of  beat,  thereby  counteracting  the  effect  on 
blood-pressure  of  the  large  vascular  dilatation  in  the  intestinal  area. 

Variations  in  Heart  Rate  with  the  Condition  of  Blood-pressure. — 
It  has  long  been  known  that  when  the  blood-pressure  in  the  arteries 
falls  the  pulse  rate  increases  and  when  it  rises  the  pulse  rate  de- 
creases. Thus,  the  low  blood-pressure  that  is  characteristic  of 
the  condition  of  surgical  shock  is  associated  with  a  very  rapid 
rate  of  heart  beat.  There  is  a  certain  inverse  relationship  between 
pressure  and  rate  which  has  the  characteristics  of  a  compensatory 
adaptation.  The  quicker  pulse  rate  following  upon  the  low  pressure 
tends  to  increase  the  output  of  blood  and  raise  the  pressure.  There 
was  formerly  much  discussion  as  to  whether  this  relationship  is 
brought  about  by  reflexes  through  the  extrinsic  nerves  of  the 

*  See  Volkmann,  "Die  Hamodynamik,"  p.  427,  1850;  also  Guy,  article 
"Pulse"  in  Todd's  "Cyclopaedia  of  Anatomy  and  Physiology,"  1847-49. 


602  CIRCULATION    OF    BLOOD    AND    LYMPH. 

heart  or  whether  it  is  due  to  some  direct,  perhaps  mechanical, 
effect  upon  the  heart.  The  experiments  of  Newell  Martin  upon 
the  isolated  heart  seem  to  have  settled  the  matter  satisfactorily.* 
By  a  method  devised  by  him  he  kept  dogs'  hearts  beating  for 
many  hours  when  isolated  from  all  connections  with  the  body 
except  the  lungs.  Under  these  conditions  it  was  found  that 
even  extreme  variations  in  blood-pressure  did  not  affect  the 
heart  rate.  Consequently,  the  variation  that  does  take  place 
under  normal  conditions  must  be  due  to  a  stimulation  of  the 
cardiac  nerves.  A  rise  of  pressure  in  the  arteries  may  affect 
directly  the  cardio-inhibitory  center  or  it  may  affect  afferent 
fibers  in  the  heart  or  arteries,  and  thus  reflexly  stimulate  the 
. cardio-inhibitory  center.  This  point  has  been  the  subject  of 
a  number  of  investigations,  but  Eyster  and  Hookerf  appear 
to  have  demonstrated  that  both  methods  of  stimulation  occur. 
High  arterial  pressure  affects  the  medullary  center  directly 
and  thus  slows  the  rate,  but  it  affects  also  certain  sensory  fibers 
in  the  aorta  at  or  beyond  the  arch,  and  through  $hem  causes  a 
reflex  slowing. 

Variations  with  Muscular  Exercise. — It  is  a  matter  of  everyday 
experience  that  the  heart  rate  increases  with  muscular  exercise. 
A  simple  change  in  posture,  in  fact,  suffices  to  affect  the  heart 
rate.  The  rate  is  higher  when  standing  (80)  than  when  sitting 
(70)  and  higher  in  this  latter  condition  than  when  lying  down 
(66).  Even  light  muscular  work,  such  as  tapping  a  telegraph  key 
as  rapidly  as  possible,  may  raise  the  heart  rate  from  60  or  70  to 
over  100  per  minute  (BowenJ),  while  the  effect  of  moderate  or 
heavy  work  is  correspondingly  greater,  the  pulse  rate  rising  to 
150,  or  even  180  per  minute.  When  the  muscular  work  is  con- 
tinued the  pulse  rate  rises  rapidly  to  a  certain  maximum,  which  it 
maintains  more  or  less  constantly  during  the  work.  After  the 
cessation  of  the  muscular  exercise  the  rate  drops  very  rapidly, 
reaching  the  normal  in  a  few  seconds  if  the  work  has  been  light, 
but  only  after  a  long  interval,  an  hour  or  more,  in  the  case  of  ex- 
hausting  muscular  work,  such  as  long-distance  runs.  Speaking  in 
general  terms,  therefore,  it  may  be  said  that  there  is  an  important 
immediate  effect  of  muscular  exercise  on  the  heart  rate,  and  a 
longer  lasting  or  relatively  permanent  effect  observed  chiefly  after 
strenuous  long-continued  exercise.  This  latter  effect  is  due,  in  all 
probability,  to  some  change  in  the  composition  of  the  blood.  One 
thinks  of  the  possibility  of  a  change  in  the  reaction  of  the  blood 
or  at  least  a  change  in  its  alkali  reserve  which  may  result  from  the 

*  Martin,  "Studies  from  the  Biological  Laboratory,  Johns  Hopkins  Uni- 
versity," 2,  213,  1882;  also  "Collected  Physiological  Papers,"  p.  25,  1895. 

f  Eyster  and  Hooker,  "American  Journal  of  Physiology,"  21,  373,  1908. 

JBowen,  "Contributions  to  Medical  Research,"  dedicated  to  V.  C. 
Vaughan,  1903. 


THE  RATE  OF  THE  HEART  BEAT.  603 

increased  formation  of  lactic  acid  in  the  contracting  muscles. 
There  is  direct  evidence  that  an  increase  in  the  hydrogen  ion  con- 
centration does  cause  an  increase  in  the  heart-rate.*  There  is  also 
the  possibility  that  other  substances  may  be  given  to  the  blood  dur- 
ing prolonged  muscular  effort  which  may  affect  the  heart  rate,  ad- 
renalin for  example.  There  is  need  for  further  experimental  work  to 
throw  light  upon  this  reaction.  The  marked  immediate  effect  of 
the  muscular  exercise  on  the  heart  rate  has  aroused  the  most  in- 
terest, and  it  has  been  studied  with  care  by  a  number  of  observers. 
The  rapidity  with  which  the  ''heart  rate  begins  to  increase  with 
muscular  work  indicates  that  it  is  a  nervous  effect  which  operates 
either  upon  the  inhibitory  apparatus,  decreasing  its  activity,  or 
upon  the  accelerator  apparatus,  increasing  its  activity.  The  ex- 
periments made  to  determine  this  latter  point  have  not  given 
concordant  results,  but  the  better  evidence  indicates  that  the  effect 
in  the  first  place  at  least  is  upon  the  cardio-inhibitory  center, 
decreasing  its  tone,  and,  therefore,  increasing  the  heart  rate. 
When,  for  example,  the  accelerator  nerves  are  excised  in  dogs,t 
moderate  exercise  causes  as  prompt  and  as  large  an  increase  in  the 
heart  rate  as  in  normal  animals.  Accepting  this  view,  the  further 
question  remains  as  to  whether  this  effect  is  an  ordinary  reflex 
action.  Some  authors  suppose  that  it  is.  They  assume  that  the 
sensory  nerves  in  the  muscles  are  stimulated,  and  that  through 
them  is  brought  about  a  reflex  inhibition  of  the  cardio-inhibitory 
center.  Others,  however,  have  suggested  that  the  effect  is  not  a 
reflex  from  the  periphery,  but  an  example  rather  of  irradiation  in 
the  nerve  centers.  J  That  is  to  say,  the  discharge  of  voluntary 
nerve  impulses  from  the  brain,  in  descending  to  the  cord,  affects 
the  cardio-inhibitory  center  in  the  medulla,  presumably,  on  the 
neuron  hypothesis,  by  way  of  collaterals.  Between  these  two 
points  of  view  it  is  not  possible  to  decide  at  present. 

Variations  with  the  Gaseous  Conditions  of  the  Blood. — In  con- 
ditions of  asphyxia  the  altered  gaseous  contents  of  the  blood, 
increase  in  CO2  and  decrease  in  O2,  act  upon  the  medullary  centers 
of  the  cardiac  nerves,  causing,  first,  an  increase  and  then  a  decrease 
in  heart  rate. 

The  Variations  in  Pulse  Rate  Due  to  Changes  in  the  Compo- 
sition or  Properties  of  the  Blood. — The  condition  under  this  head 
that  has  the  most  marked  influence  upon  the  heart  rate  is  the 
temperature  of  the  blood.     Speaking  generally,  the  rate  of  beat 
increases  regularly  with  the  temperature  of  the  blood  or  other 
circulating  liquid  up  to  a  certain  optimum  temperature.    On  the 
heart  of  the  cold-blooded  animal  this  relationship  is  easily  demon- 
looker,  Wilson,  Connett,  "Amer.  Jour,  of  Phys.,"  43,  351,  1917. 
t  Gasser  and  Meek,  "Amer.  Jour,  of  Phys.,"   34,  48,  1914. 
}  Johannson,  "  Skandinavisches  Archiv  f .  Physiologic,/'  5,  20,  1885. 


604 


CIRCULATION    OF    BLOOD    AND    LYMPH. 


strated  by  supplying  the  heart  with  an  artificial  circulation  of 
Ringer's  solution,  which  can  be  heated  or  cooled  at  pleasure.  The 
rate  and  force  of  the  beat  increase  to  a  maximum,  which  is 
reached  at  about  30°  C.  (see  Fig.  247).  Beyond  this  optimum 
temperature  the  beats  decrease  in  force  and  also  in  rate,  becoming 
irregular  or  fibrillar  before  the  heart  finally  comes  to  rest.  Newell 
Martin*  has  shown  the  same  relationship  in  a  very  conclusive 
way  upon  the  isolated  heart  of  the  dog.  Within  physiological 

limits  the  rate  of  beat  rises  and 
falls  substantially  parallel  to  the 
variations  in  temperature  as  is 
shown  by  the  chart  reproduced  in 
Fig.  248.  The  accelerated  heart 
rate  in  fevers  is  therefore  due 
probably  to  the  direct  influence  of 
the  high  temperature  upon  the 
heart  itself.  The  same  observer  de- 
termined experimentally  the  upper 
and  lower  lethal  limits  of  tempera- 
ture for  the  mammalian  heart. 
The  experiments  were  made  upon 
cats'  hearts  kept  alive  by  artificial 
circulation  through  the  coronary 
arteries,  t  It  was  found  that  the 
highest  temperature  at  which  the 
heart  will  beat  is  about  44°  to 
45°  C.,  although  a  slightly  higher 
temperature  may  be  withstood 
under  special  conditions.  At  the 
other  extreme  the  mammalian 
heart  ceases  to  beat  when  the 
temperature  falls  as  low  as  17°  to 
18°  C. 

The  rate  of  the  heart  beat  may 
be  influenced  also  by  many  sub- 
stances added  to  the  blood.  The 
influence  of  atropin  and  muscarin 
has  already  been  alluded  to,  but 
changes  also  in  the  normal  con- 
stituents of  the  blood  may  have  similar  effects.  An  increased  out- 
put of  epinephrin  from  the  adrenal  glands,  such  as  may  result  from 
emotional  excitement  (p.  625),  will  modify  the  heart  beat  either 

*  Martin,  "Croonian 
London,  174,  663,  1883; 

f  Martin  and  Applegarth 
Hopkins  University," 
p.  97,  1895. 


Fig.  247.— To  show  the  effect  of 
temperature  on  the  rate  and  force  01 
the  heart  beat.  Contractions  of  the 
terrapin's  ventricle  at  different  tem- 
peratures. Kymograph  moving  at 
the  same  speed.  At  30°  the  rate  it> 
still  increasing,  but  the  extent  of  con- 
traction has  passed  its  optimum. 


4,  275,  1890;  also  "Collected  Physiological  Papers," 


THE  RATE  OF  THE  HEART  BEAT. 


605 


directly  or  through  the  cardio-inhibitory  center  of  the  medulla, 
and  distinct  variations  in  the  reaction  or  the  inorganic  constituents 
of  the  blood  may  also  affect  the  rhythm  of  the  heart.  Addition  of 
potassium  salts  in  excess  will  stop  the  heart  beat  entirely,  bringing 
about  the  condition  of  potassium  inhibition,  but  such  conditions 
are,  for  the  most  part,  exceptional  or  experimental.  In  the  usual 


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routine  of  life  the  heart  beat  is  regulated  and  adapted  to  the  needs 
of  the  body  chiefly,  as  far  as  we  know,  through  the  agency  of  its 
extrinsic  nerves  rather  than  through  modifications  of  the  com- 
position of  the  blood. 


CHAPTER  XXXII. 

THE  VASOMOTOR  NERVES  AND  THEIR  PHYSIO- 
LOGICAL  ACTIVITY, 

During  the  first  half  of  the  nineteenth  century  the  physical  or 
mechanical  conditions  of  the  circulation  were  carefully  studied  and 
great  emphasis  was  laid  upon  such  properties  as  the  elasticity  of 
the  coats  of  the  vessels.  The  physical  adaptability  thereby  con- 
ferred upon  the  vascular  tubes  was  thought  to  be  sufficient  for  the 
purposes  of  the  circulation.  We  now  know  that  many  of  the  blood- 
vessels are  supplied  with  motor  and  inhibitory  nerve  fibers  through 
whose  activity  the  size  of  the  vascular  bed  and  the  distribution  of 
blood  to  the  various  organs  are  regulated.  We  know,  also,  that 
without  this  nervous  control  the  vascular  system  fails  entirely  to 
meet  what  seems  to  be  the  most  important  condition  of  a  normal 
circulation, — namely,  the  maintenance  of  a  high  arterial  pressure. 
Although  a  number  of  physiologists  had  assumed  the  existence  of 
nerve  fibers  capable  of  acting  upon  the  muscular  coats  of  the  blood- 
vessels, the  experimental  proof  of  the  existence  of  such  nerves, 
and  the  beginning  of  the  modern  development  of  the  theory  of 
vasomotor  regulation  were  a  part  of  the  brilliant  contributions  to 
physiology  made  by  Claude  Bernard.*  In  1851  Bernard  discovered 
that  when  the  sympathetic  nerve  is  cut  in  the  neck  of  a  rabbit  the 
blood-vessels  in  the  ear  on  the  same  side  become  very  much  dilated. 
He  and  other  observers  afterward  showed  that  if  the  peripheral 
(head)  end  of  the  severed  nerve  is  stimulated  electrically  the  ear 
becomes  blanched,  owing  to  a  constriction  of  the  blood-vessels. 
Thus  the  existence  of  vasoconstrictor  nerve  fibers  to  the  blood-vessels 
was  demonstrated.  A  vast  amount  of  experimental  work  has  been 
done  since  to  ascertain  the  exact  distribution  of  these  fibers  to  the 
various  organs  and  the  reflex  conditions  under  which  they  function 
normally.  Few  subjects  in  physiology  are  of  more  practical  im- 
portance to  the  physician  than  that  of  vasomotor  regulation;  it 
plays  such  a  large  and  constant  part  in  the  normal  activity  of  the 
various  organs.  Bernard  was  doubly  fortunate  in  being  the  first 
to  demonstrate  the  existence  of  a  second  class  of  nerve  fibers,  which, 
when  stimulated,  cause  a  dilatation  of  the  blood-vessels  and  which 

*  See  "Life  of  Claude  Bernard,"  by  Sir  Michael  Foster,  1899,  in  the  series, 
"Masters  of  Medicine." 

606 


THE    VASOMOTOR    NERVES.  607 

are  therefore  designated  as  vasodilator  nerve  fibers.  This  discovery 
was  made  in  connection  with  the  chorda  tympani  nerve,  a  branch 
of  the  facial,  which  sends  secretory  fibers  to  the  submaxillary  gland. 
When  this  nerve  is  cut  and  the  peripheral  end  is  stimulated  a  secre- 
tion of  saliva  results  and  at  the  same  time,  as  Bernard  showed,  the 
blood-vessels  of  the  gland  dilate;  the  flow  of  blood  is  greatly  in- 
creased in  the  efferent  vein  and  may  even  show  a  pulse. 

In  the  nervous  regulation  of  the  blood-vessels  we  have  to  con- 
sider, therefore,  the  existence  and  physiological  activities  of  two 
antagonistic  sets  of  nerve  fibers:  First,  the  vasoconstrictor  fibers, 
whose  action  causes  a  contraction  of  the  muscular  coats  of  the  ar- 
teries and  therefore  a  diminution  in  the  size  of  the  vessels.  Second, 
the  vasodilator  nerve  fibers,  whose  action  causes  an  increase  in  size 
of  the  blood-vessels,  due  probably  to  a  relaxation  (inhibition)  of  the 
muscular  coats  of  the  arteries.  Before  attempting  to  describe  the 
present  state  of  our  knowledge  upon  these  points  it  will  be  help- 
ful to  refer  to  some  of  the  methods  by  means  of  which  the  existence 
of  vasomotor  fibers  has  been  demonstrated. 

Methods  Used  to  Determine  Vasomotor  Action. — The 
simplest  and  most  direct  proof  is  obtained  from  mere  inspection, 
when  this  is  possible.  If  stimulation  of  the  nerve  to  an  organ 
causes  it  to  blanch,  the  presence  of  vasoconstrictor  fibers  is  dem- 
onstrated unless  the  organ  is  muscular  and  the  blanching  may  be 
regarded  as  a  mechanical  result.  On  the  other  hand,  if  stimulation 
of  the  nerve  to  an  organ  causes  it  to  become  congested  or  flushed 
with  blood  the  presence  of  vasodilator  fibers  may  be  accepted.  It 
is  obvious,  however,  that  this  method  is  applicable  in  only  a  few 
instances  and  that  in  no  case  does  it  lend  itself  to  quantitative 
study.  2.  Vasomotor  effects  may  be  determined  by  measur- 
ing the  outflow  of  blood  from  the  veins.  If  stimulation  of  the 
nerve  to  an  organ  causes  a  decrease  in  the  flow  of  blood  from  the 
veins  of  that  organ,  this  fact  implies  the  existence  of  vasoconstrictor 
fibers,  while  an  opposite  result  indicates  vasodilator  fibers.  3. 
By  variations  in  arterial  and  venous  pressures.  When  vaso- 
constrictor fibers  are  stimulated  there  is  a  rise  of  pressure  in  the 
artery  supplying  the  organ  and  a  fall  of  pressure  in  the  veins 
emerging  from  the  organ.  This  result  is  what  we  should  expect  if 
the  constriction  takes  place  in  the  region  of  the  arterioles.  The 
diminution  in  size  of  these  vessels  by  increasing  peripheral  resistance 
augments  the  internal  pressure  on  the  arterial  side  of  the  resistance, 
and  causes  a  fall  of  side  pressure  on  the  venous  side  (see  p.  515). 
If  the  area  involved  is  large  enough  the  increased  resistance  will 
make  a  perceptible  difference  in  pressure,  not  only  in  the  organ 
supplied,  but  also  in  the  aorta;  there  will  be  a  rise  of  general  (dias- 
tolic)  blood-pressure.  On  the  other  hand,  a  vasodilator  action  IP 


608  CIRCULATION    OF    BLOOD    AND    LYMPH. 

any  organ  is  accompanied  by  the  reverse  changes.  Peripheral 
resistance  being  diminished  there  will  be  a  fall  of  pressure  on  the 
arterial  side  and  a  rise  of  pressure  on  the  venous  side.  When, 
therefore,  the  stimulation  of  any  nerve  brings  about  a  rise  of 
arterial  pressure  that  can  not  be  referred  to  a  change  in  the  heart 
beat  the  inference  made  is  that  the  result  is  due  to  a  vasocon- 
striction.  When  the  method  is  applied  to  a  definite  organ — the 
brain,  for  instance — it  becomes  conclusive  only  when  simultaneous 
observations  are  made  upon  the  pressure  in  the  artery  and  the  vein 
of  the  organ,  and  proof  is  obtained  that  the  pressures  at  these  points 
vary  in  opposite  directions.  4.  By  observations  upon  the  volume 
of  the  organ.  It  is  obvious  that,  other  conditions  remaining  un- 
changed, a  vasoconstriction  in  an  organ  will  be  accompanied  by 
a  diminution  in  volume,  and  a  vasodilatation  by  an  increase  in 
volume.  This  method  of  studying  the  blood-supply  of  an  organ  is 
designated  as  plethysmography,  and  any  instrument  designed  to 
record  the  changes  in  volume  of  an  organ  is  a  plethysmograph* 
Plethysmographs  have  been  designed  for  special  organs,  and  in  such 
cases  they  have  sometimes  been  given  special  names.  Thus,  the 
plethysmograph  used  upon  the  kidney  and  spleen  has  been  desig- 
nated as  an  oncometer,  that  for  the  heart,  as  a  cardiometer. 
The  precise  form  and  structure  of  a  plethysmograph  varies,  of 
course,  with  the  organ  studied,  but  the  principle  used  is  the 
same  in  all  cases.  The  organ  is  inclosed  in  a  box  with  rigid 
walls  that  have  an  opening  at  some  one  point  only,  and  this 
opening  is  placed  in  connection  with  a  recorder  of  some  kind  by 
tubing  with  rigid  walls.  The  connections  between  recorder 
and  plethysmograph  and  the  space  in  the  interior  of  the  latter 
not  occupied  by  the  organ  may  be  filled  with  air  or,  as  is  more 
usually  the  case,  with  water.  The  idea  of  a  plethysmograph 
may  be  illustrated  by  the  skull.  This  structure  forms  a  natural 
pelthysmograph  for  the  brain.  If  a  hole  is  bored  through  the 
skull  at  any  point  and  a  connection  is  then  made  with  a  recorder 
of  some  kind,  such  as  a  tambour,  the  volume  changes  of  the 
brain  may  be  registered  successfully. 

The  plethysmograph  generally  em  ployed  in  laboratories,  particularly  for  in- 
vestigations on  man,  is  some  modification  of  the  form  devised  by  Mosso  (see 
Fig.  249) .  The  hand  and  more  or  less  of  the  arm  is  placed  in  a  glass  cylinder 
which  is  swung  freely  from  a  support.  The  opening  around  the  arm  is  shut 
off  by  a  cuff  of  rubber  dam  that  must  be  chosen  of  such  a  size  as  to 
fit  the  arm  snugly  without  compression  of  the  superficial  veins.  The 
forward  end  of  the  plethysmograph  is  connected  by  tubing  with  a  re- 
corder. Through  appropriate  openings  the  cylinder  and  connecting  tubes 
are  filled  with  warm  water  and  then  all  openings  are  closed  except  the 
one  leading  to  the  recorder.  Any  increase  in  volume  of  the  arm  will  drive 
water  from  the  plethysmograph  to  the  recorder,  and  any  decrease,  on 

*  For  a  description  of  the  development  of  this  method,  see  Francjois-Franck- 
Marey's  "Travaux  du  Laboratoire/'  1876,  p.  1. 


THE    VASOMOTOR    NERVES. 


609 


the  contrary,  will  suck  water  from  the  recorder  into  the  plethysmograph. 
In  the  author's  laboratory  a  modification  that  has  been  found  most  conve- 
nient is  represented  in  Fig.  250.  To  avoid  escape  of  water  at  the  upper  end 
of  the  tube  and  at  the  same  time  to  prevent  compression  of  the  veins  of  the 
arm  a  very  thin  rubber  glove  with  long  gauntlet  is  used.  The  gauntlet 
is  strengthened  by  cuffs  of  dam  tubing,  as  shown  in  the  illustration,  and  all 
are  reflected  over  the  end  of  the  plethysmograph.  The  outer  cuff  (3)  may 
be  omitted.  The  hand  is  inserted  into  the  cylinder  and  is  held  in  place  by 
flexing  the  fingers  through  the  rings.  The  plethysmograph  being  suspended 
freely  from  the  ceiling,  any  movement  of  the  arm  will  move  the  instrument  as 
a  whole  without  disturbing  the  position  of  the  arm  in  the  instrument.  By 
means  of  rings  of  hard  rubber  (D,  E) ,  one  fitting  around  the  rim  of  the  plethys- 
mograph and  the  other  adapted  more  or  less  closely  to  the  size  of  the  forearm, 
the  reflected  portion  of  the  gauntlet  and  cuff  is  held  in  place  and  prevented 
from  giving  way  readily  to  any  rise  of  pressure  in  the  plethysmograph.  The 


Fig.  249. — A  schematic  diagram  of  Mosso's  plethysmograph  for  the  arms:  a,  the  glass 
cylinder  for  the  arm,  with  rubber  sleeve  and  two  tubulatures  for  filling  with  warm  water ; 
8,  the  spiral  spring  swinging  the  test  tube,  t.  The  spring  is  so  calibrated  that  the  level  of 
the  liquid  in  the  test  tube  above  the  arm  remains  unchanged  as  the  tube  is  filled  and 
emptied.  The  movements  of  the  tube  are  recorded  on  a  drum  by  the  writing  point,  p. 


ulterior  of  the  latter  is  connected,  as  shown  in  Fig.  249,  to  a  test  tube  swung 
by  a  spiral  spring  (Bowditch's  recorder) .  The  spring  is  so  adjusted  by  trial  that 
it  suiks  and  rises  exactly  in  proportion  to  the  inflow  or  outflow  of  water.  By 
this  means  the  level  of  the  water  in  the  tube  is  kept  constant,  and  since  the  posi- 
tion of  this  level  determines  the  pressure  upon  the  outside  of  the  arm  in  the 
plethysmograph  this  pressure  is  also  kept  constant  independently  of  the 
changes  in  volume  of  the  arm.  The  level  should  be  set  in  the  beginning 
so  as  to  make  a  slight  positive  pressure  on  the  arm  sufficient  to  flatten 
the  thin  glove  to  the  skin  and  thus  drive  out  the  air  between  the  two. 
When  the  apparatus  is  conveniently  arranged,  with  slings  to  support  the 
elbow,  observations  may  be  made  upon  the  changes  in  volume  of  the  arm 
during  long  periods.  The  results  so  obtained  are  referred  to  under  several 
headings.  With  the  form  of  recorder  described  the  plethysmograph  gives 
usually  only  the  slow  changes  hi  volume  of  the  arm,  due  to  a  greater  or  less 
amount  of  blood.  By  using  a  more  sensitive  recorder  and  making  the  con- 

39 


610  CIRCULATION    OF    BLOOD    AND    LYMPH 

nections  entirely  rigid  the  smaller,  quicker  changes  in  volume  caused  by  the 
heart  beat  are  also  recorded.  A  volume  pulse  is  obtained  resembling  in  its 
general  form  the  pressure  pulse  given  by  the  sphygmograph.  When  used 
For  this  purpose  the  instrument  is  described  as  a  hydrosphygmograph. 

Records  taken  of  the  volume  of  the  hand,  foot,  brain,  or  any 
other  organ  show  that  in  addition  to  the  changes  caused  by  the 
heart  beat  and  by  the  respiratory  movements,  there  are  other  more 
irregular  variations  that  are  continually  occurring,  the  cause  of  which 
is  to  be  found  in  the  variations  in  the  amount  of  blood  in  the  organ. 
Day  and  night  these  changes  in  volume  take  place,  and  they  are 
referable  to  the  activity  of  the  vasomotor  system.  Vasoconstriction 
or  vasodilatation  in  the  organ  itself  cause  what  may  be  called 


Fig.  250. — Detailed  drawing  of  the  glass  plethysmograph  with  the  arrangement  of  rub- 
ber glove  to  prevent  leaking  without  com  pressing  the  veins.  2.  The  glove  with  its  gauntlet 
reflected  over  the  end  of  the  glass  cylinder;  1  and  3,  supporting  pieces  ol  stout  rubber  tub- 
ing ;  D  and  E,  sections  of  outer  and  inner  rings  of  hard  rubber  to  fasten  the  reflected  rubber 
tubing  and  reduce  the  opening  for  the  arm. 

an  active  change  in  volume.  But  Vasoconstriction  or  vasodilata- 
tion in  other  organs  may  cause  a  perceptible  change,  of  a  passive 
kind,  in  the  volume  of  the  organ  under  observation.  For,  since 
the  amount  of  blood  remains  the  same,  a  change  in  any  one  organ 
must  affect  more  or  less  the  volume — that  is,  the  blood  contents — 
of  all  other  organs. 

General  Distribution  and  Course  of  the  Vasoconstrictor 
Nerve  Fibers. — These  fibers  belong  to  the  sympathetic  autonomic 
system,  and  consist,  therefore,  of  a  preganglionic  fiber  arising  in  the 
central  nervous  system  and  a  postganglionic  fiber  arising  from  the 
cell  of  some  sympathetic  ganglion.  The  general  arrangement  of 
the  autonomic  system  (p.  252)  should  be  reviewed  in  this  connec- 
tion. It  has  been  shown  by  experiments  of  the  kind  described 
under  the  last  heading  that  vasoconstrictor  fibers  are  present  in 


THE    VASOMOTOR    NERVES. 


611 


numerous  nerve  trunks,  but  especially  in  those  distributed  to  the 
skin  and  to  the  abdominal  and  pelvic  organs.  If,  for  instance,  the 
sciatic  or  the  splanchnic  nerve  be  cut,  to  avoid  reflex  effects,  and 
the  peripheral  end  be  stimulated,  there  will  be  a  strong  constriction 
of  the  vessels,  which  may  be  detected  by  ocular  inspection,  blanch- 
ing; by  the  increase  in  arterial  pressure;  or  by  the  diminution  in 
volume  of  the  organs.  The  vasoconstrictor  fibers  supplying  these 
two  great  regions  arise  immediately  (postganglionic  fibers)  from 
one  or  other  of  the  ganglia  constituting  the  sympathetic  chain,  or 
from  the  large  prevertebral  ganglia  (celiac  ganglion,  for  instance) 
directly  connected  with  it.  Ultimately,  of  course,  they  arise  in  the 
central  nervous  system  (preganglionic  fiber),  and  it  has  been  shown 
that,  for  the  regions  under  consideration,  they  all,  with  a  few  com- 
paratively unimportant  exceptions,  leave  the  spinal  cord  in  the 
great  outflow  that  takes  place  in  the  thoracic  region  from  the  second 


Fig.  251. — Schema  to  show  the  path  of  the  preganglionic  and  postganglionic  portions 
of  a  vasoconstrictor  nerve  fiber:  a,  Anterior  root,  showing  the  course  of  the  preganglionic 
fiber  as  a  dotted  line;  d,  v,  dorsal  and  ventral  branches  of  the  bpinal  nerve;  r,  the  ramus 
communicans;  g,  the  sympathetic  ganglion.  The  postgangliocic  fibers  in  each  ramus  come 
from  the  sympathetic  ganglion  with  which  it  is  connected.  The  preganglionic  fibers  enter- 
ing at  any  ganglion  may  pass  up  or  down  to  end  in  the  cells  of  some  other  ganglion. 


thoracic  to  the  second  lumbar  nerves  (p.  254).  In  this  outflow 
they  are  mixed  with  other  autonomic  fibers,  such  as  the  sweat 
fibers,  pilomotor  fibers,  accelerator  fibers  to  heart,  pupilodilator 
fibers,  visceromo tor  fibers,  etc.  Emerging  in  the  anterior  roots,  they 
pass  to  the  sympathetic  chain  by  way  of  the  corresponding  ramus 
communicans.  Having  reached  the  chain,  they  end  in  one  or  other 
of  the  ganglia,  not  necessarily  in  the  ganglion  with  which  the  ramus 
connects  anatomically.  The  preganglionic  fibers  for  the  blood- 
vessels of  the  submaxillary  gland,  for  instance,  enter  the  first 
thoracic  ganglion  of  the  sympathetic  chain,  but  do  not  actually 
terminate  until  they  reach  the  superior  cervical  ganglion  high  in  the 
neck.  The  postganglionic  fibers  arise  in  the  ganglion  in  which  the 
preganglionic  fibers  terminate.  Those  destined  to  supply  the  skin 


612  CIRCULATION    OF    BLOOD    AND    LYMPH. 

of  the  trunk  and  extremities  pass  from  the  ganglion  to  the  cor- 
responding spinal  nerve  by  way  of  the  ramus  communicans  (gray 
ramus)  and  after  reaching  the  spinal  nerve  they  are  distributed  with 
it  to  its  corresponding  region  (Fig.  251).  In  the  general  region 


Fig.  252. — Vasomotor  effect  of  stimulation  of  the  splanchnic  nerve — peripheral  end — 
in  the  dog  (Dawaon) :  1.  The  line  of  zero  pressure;  2,  the  line  of  the  stimulating  pen;  on 
and  off  mark  the  beginning  and  end  of  the  stimulation;  3,  the  time  record  in  seconds;  4, 
the  blood-pressure  record  (stimulation  causes  a  marked  rise  of  blood-pressure  due  to  stimu- 
lation of  vasoconstrictor  fibers) ;  5,  plethysmographic  tracing  of  the  volume  of  the  kidney 
(oncometer);  stimulation  of  the  splanchnic  causes  a  diminution  in  volume  of  the  kidney 
owing  to  the  constriction  of  its  arterioles. 

under  consideration  (lower  cervical  to  upper  lumbar)  each  ramus 
communicans  between  a  spinal  nerve  and  a  sympathetic  ganglion 
consists,  therefore,  of  two  parts,  one  (white  ramus)  of  preganglionic 
fibers  passing  from  the  spinal  nerve  to  the  ganglion,  the  other 
(gray  ramus)  of  postganglionic  fibers  coming  from  the  ganglion  to 
the  spinal  nerve  for  distribution  to  the  peripheral  tissues.  It  should 
be  borne  in  mind  that  the  fibers  in  the  white  ramus  do  not 
return  to  the  spinal  nerve  by  the  gray  portion  of  the  same  ramus, 


THE    VASOMOTOR    NERVES.  613 

but  passing  upward  or  downward  in  the  sympathetic  chain 
return,  to  some  other  spinal  nerve  as  postganglionic  fibers.  In  this 
way,  therefore,  it  happens  that  the  various  intercostal  nerves  and 
the  nerves  of  the  brachial  and  sciatic  plexus  contain  vasoconstrictor 
fibers  as  postganglionic  or  sympathetic  fibers.  On  the  other  hand, 
the  vasoconstrictor  fibers  destined  for  the  great  vascular  region  of 
the  intestines  and  other  abdominal  viscera,  after  reaching  the  sym- 
pathetic chain  by  way  of  the  white  rami  as  preganglionic  fibers,  do 
not  return  to  the  spinal  nerves  by  the  gray  rami.  They  leave  the 
sympathetic  chain,  still  as  preganglionic  fibers,  in  the  branches  of  the 
splanchnic  nerves  and  through  them  pass  to  the  celiac  ganglion, 
where  they  mainly  end,  and  their  path  is  continued  by  the  post- 
ganglionic or  sympathetic  fibers  arising  from  this  ganglion.  More 
specific  information  concerning  the  origin  of  the  vasomotor  fibers 
to  the  different  organs  is  given  in  condensed  form  farther  on.  It  is 
quite  important  in  the  beginning,  however,  to  obtain  a  clear  general 
conception  of  the  paths  taken  by  the  constrictor  fibers  from  their 
origin  in  the  spinal  cord  to  their  termination,  on  the  one  hand, 
in  the  vessels  of  the  skin,  or,  on  the  other,  in  the  vessels  of  the 
abdominal  and  pelvic  viscera. 

The  Tonic  Activity  of  the  Vasoconstrictor  Fibers. — A  very 
important  fact  regarding  the  vasoconstrictor  nerve  fibers  is  that 
they  are  constantly  in  action  to  a  greater  or  less  extent.  This 
fact  is  demonstrated  by  the  simple  experiment  of  cutting  them. 
If  the  sympathetic  nerve  in  the  neck  is  cut  in  the  rabbit  the  blood- 
vessels of  the  ear  become  dilated.  If  the  splanchnic  nerves  on 
the  two  sides  are  cut  the  intestinal  region  becomes  congested, 
and  the  effect  in  this  case  is  so  great  that  the  general  arterial  pressure 
falls  to  a  very  low  point.  From  these  and  numerous  similar  ex- 
periments we  may  conclude  that  normally  the  arteries — that  is, 
the  arterioles — are  kept  in  a  condition  of  tone  by  impulses  received 
through  the  vasoconstrictor  fibers.  Cut  these  nerves  and  the  arte- 
ries lose  their  tone  and  dilate,  with  the 'result  that,  the  peripheral 
resistance  being  diminished,  the  lateral  pressure  falls  on  the  arterial 
side  and  rises  on  the  venous  side.  The  relatively  enormous  effect 
upon  aortic  pressure  caused  by  paralysis  of  the  tone  of  the  arteries 
in  the  splanchnic  area  shows  that  under  normal  conditions  the 
peripheral  resistance  in  this  great  area  plays  a  predominant  part 
in  the  maintenance  of  normal  arterial  pressure,  and  by  the  same 
reasoning  variations  in  tone  in  the  arteries  of  this  region  must 
play  a  very  large  part  in  the  regulation  of  arterial  pressure. 

The  Vasoconstrictor  Center. — As  stated  in  the  last  two  para- 
graphs, the  vasoconstrictor  fibers  emerge  from  the  cord  over  a 
definite  region,  and  they  exhibit  constant  tonic  activity.  It  has 
been  shown,  moreover,  that  if  the  cord  be  cut  anywhere  in  the 


614 


CIRCULATION    OF    BLOOD    AND    LYMPH. 


cervical  region  all  of  the  constrictor  fibers  lose  their  tone;  a  great 
vascular  dilatation  results  in  both  the  splanchnic  and  skin  areas. 
We  may  infer  from  this  fact  that  the  vasoconstrictor  paths  originate 
from  nerve  cells  in  the  brain  and  that  their  tonic  activity  is  to 
be  traced  to  these  cells.  Such  a  group  of  cells  exists  in  the  medulla 

oblongata,  and  forms  the  vaso- 
constrictor center.  The  axons 
given  off  from  these  cells  de- 
scend in  the  cervical  cord  and 
terminate  at  various  levels  in 
the  anterior  horn  of  gray  mat- 
ter in  the  region  from  the  upper 
thoracic  to  the  upper  lumbar 
spinal  nerves.  A  spinal  neuron 
continues  the  path  as  the  pre- 
ganglionic  vasoconstrictor  fiber 
which  terminates,  as  already 
described,  in  some  sympathetic 
ganglion,  whence  the  path  is 
further  continued  by  the  post- 
ganglionic  fiber.  This  arrange- 
ment of  the  constrictor  paths  is 
indicated  schematically  in  Fig. 
253.  The  exact  location  of  the 
group  of  cells  that  plays  the  im- 
portant role  of  a  vasoconstrictor 
center  has  not  been  determined 
histologically.  The  region  has, 
however,  been  delimited  roughly 
by  physiological  experiments.  If 
the  brain  is  cut  through  at  the 
level  of  the  midbrain  there  is  no 
marked  loss  of  vascular  tone  in 
the  body  at  large.  If,  however, 
similar  sections  are  made  farther 
and  farther  back  a  point  is 

reached  at  which  vascular  paralysis  begins  to  be  apparent  and  a 
point  farther  down  at  which  this  paralysis  is  as  complete  as  it 
would  be  if  the  cervical  cord  were  cut.  Between  these  two  points 
the  vasoconstrictor  center  must  lie.  The  careful  experiments  of 
this  kind  made  by  Dittmar*  are  now  somewhat  old.  According 
to  his  description,  the  center  is  bilateral, — that  is,  consists  of  a 
group  of  cells  on  each  side, — and  lies  about  the  middle  of  the  fourth 
ventricle  in  the  tegmental  region,  in  the  neighborhood  of  the  nucleus 
of  the  facial  and  of  the  superior  olivary.  In  the  rabbit  it  has  a 
*  "Berichte  d.  Sachs.  Akademie,  Math.-phys.  Klasse,"  1873,  p.  449. 


Fig.  253.— Schema  to  show  the  path 
of  the  vasoconstrictor  fibers  from  the  vaso- 
constrictor center  to  the  blood-vessels  and 
the  mechanism  for  the  reflex  stimulation 
of  these  fibers :  v.  c.,  The  vasoconstrictor 
center;  1,  the  central  neuron  of  the  vaso- 
constrictor path ;  2,  the  spinal  neuron 
(preganglionic  fiber);  3,  the  sympathetic 
neuron  (postganglionic  fiber);  a,  the  arte- 
riole ;  4,  the  sensory  fibers  of  the  posterior 
root  making  connections  by  collaterals 
with  the  vasoconstrictor  center ;  5,  an  in- 
tercentral  fiber  (efferent)  acting  upon  the 
vasoconstrictor  center. 


THE    VASOMOTOR    NERVES.  615 

length  of  3  mms.,  a  breadth  of  1  to  1.5  mms.,  and  lies  about  2 
to  2.5  mms.  lateral  to  the  mid-line.  Assuming  the  existence  of 
this  group  of  cells,  we  must  attribute  to  them  functions  of  the  first 
importance.  Like  other  motor  cells,  they  are  capable  of  being 
stimulated  reflexly  and  by  this  means  the  regulation  of  the  blood- 
flow  is  largely  controlled.  Moreover,  they  are  in  constant  activity, 
• — due  doubtless  also  to  a  constant  reflex  stimulus  from  the  inflow 
of  afferent  impulses.  The  complete  loss  of  this  tonic  influence 
would  result  in  a  complete  vascular  paralysis,  the  small  arteries 
would  be  dilated,  peripheral  resistance  would  be  greatly  diminished, 
and  the  arterial  pressure  in  the  aorta  would  fall  from  a  level  of 
100-150  mms.  Hg  to  about  20  or  30  mms.  Hg, — a  pressure  insuffi- 
cient to  maintain  the  life  of  the  organism.  We  must  conceive, 
also,  that  in  this  vasoconstrictor  center  the  different  cells  are  con- 
nected by  definite  paths  with  the  vasoconstrictor  fibers  to  the 
different  regions  of  the  body;  that  some  of  the  cells,  for  instance, 
control  the  activity  of  the  fibers  distributed  to  the  intestinal  area, 
and  others  govern  the  vessels  of  the  skin.  Under  physiological 
conditions  the  different  parts  of  the  center  may,  of  course,  be  acted 
upon  separately.  In  this  description  of  the  vasoconstrictor  center 
and  the  efferent  vasoconstrictor  fibers  reference  has  been  made  only 
to  their  action  on  the  small  arteries.  This  is,  generally  speaking, 
the  apparatus,  which  on  the  basis  of  experimental  work,  we  are 
justified  in  using  to  explain  the  various  vasomotor  phenomena  of 
the  body.  There  are,  however,  many  observations  on  record 
which  indicate  the  possibility  that  the  veins  also  may  be  supplied 
with  motor  nerve  fibers,  and  that  reflex  control  of  the  distribution 
of  the  blood  and  the  regulation  of  the  return  flow  to  the  heart  may 
be  exerted  in  part  through  changes  in  the  caliber  of  the  venous 
vessels.  Unfortunately,  our  knowledge  upon  this  point  is  too  in- 
complete at  present  to  be  used  with  confidence  in  the  explanation 
of  specific  phenomena.  It  is,  nevertheless,  a  possibility  that  must 
be  held  in  mind.  Some  of  the  more  significant  facts  bearing  upon 
this  point  are  referred  to  below. 

Vasoconstrictor  Reflexes — Pressor  and  Depressor  Nerve 
Fibers. — It  is  obvious  that  such  a  mechanism  as  that  described 
above  is  susceptible  of  reflex  stimulation  through  sensory  nerves, 
and  according  to  our  general  knowledge  we  should  suppose  that 
a  tonic  center  of  this  kind  may  have  its  tonicity  increased  (excita- 
tion) or  decreased  (inhibition).  Numerous  experiments  in  phys- 
iology warrant  the  view  that  both  kinds  of  effect  take  place 
normally.  Those  afferent  nerve  fibers  which  when  stimulated 
cause  reflexly  an  excitation  of  the  vasoconstrictor  center,  and 
therefore  a  peripheral  vasoconstriction  and  rise  of  arterial  pressure, 
are  frequently  designated  as  pressor  fibers,  or  their  effect  upon  the 
circulation  is  designated  as  a  pressor  effect.  Those  afferent  fibers, 


616  CIRCULATION    OF    BLOOD    AND    LYMPH. 

on  the  contrary,  which  when  stimulated  cause  a  diminution  in 
the  tone  of  the  vasoconstrictor  center  and  therefore  a  periph- 
eral vasodilatation  and  fall  of  arterial  pressure,  are  designated  as 
depressor  nerve  fibers,  or  their  effect  upon  the  circulation  is  a  de- 
pressor effect.  Pressor  effects  may  be  obtained  by  stimulation  of 
almost  any  of  the  large  nerves  containing  afferent  fibers,  but  espe- 
cially perhaps  of  the  cutaneous  nerves.  There  is  abundance 
of  evidence  to  show  that  similar  results  can  be  obtained  in  man. 
The  pressor  effect  manifests  itself  by  a  rise  in  general  arterial  pres- 
sure, if  a  sufficiently  large  region  is  involved,  and  by  a  diminution 
in  size  of  the  organ  involved.  On  the  other  hand,  depressor  effects 
may  also  be  obtained  from  stimulation  of  many  of  the  large  nerve 
trunks.  If  one  stimulates  the  central  end  of  the  sciatic  nerve, 
for  example,  one  obtains  a  pressor  effect  on  the  circulation  in  most 
cases,  but  under  certain  conditions  a  marked  depressor  effect  fol- 
lows the  stimulation.*  The  simplest  explanation  of  such  a  result 
is  that  the  nerve  trunks  contain  afferent  fibers  of  both  kinds. 
When  we  apply  our  electrodes  to  a  nerve  we  stimulate  every  fiber 
in  it  and  the  actual  result  will  depend  upon  which  group  of  fibers 
exerts  the  stronger  action,  and  this  may  vary  with  the  condition 


Fig.  254.— Plethysmographic  curve  of  forearm.  The  volume  of  the  arm  was  recorded 
by  means  of  a  counter-weighted  tambour  and  the  record  shows  the  pulse  waves.  A  problem 
in  mental  arithmetic — the  product  of  24  by  43  —caused  a  marked  constriction  of  the  arm. 

of  the  nerve,  the  condition  of  the  center,  the  anesthetic  used,  etc. 
Under  normal  conditions  no  such  gross  stimulation  occurs.  The 
pressor  fibers  are  stimulated  under  some  circumstances,  the  de- 
pressor fibers  under  others.  For  instance,  when  the  skin  is  exposed 
to  cold  it  is  blanched  not  by  a  direct,  but  by  a  reflex,  effect.  The 
low  temperature  stimulates  the  sensory  (cold)  fibers  in  the  skin, 
and  the  nerve  impulses  thus  aroused  reflexly  stimulate  the  vaso- 
constrictor center,  or  a  part  of  it,  and  cause  blanching  of  the  skin. 
Exposure  to  high  temperatures,  on  the  contrary,  flushes  the  skin, 
*See  Hunt,  "  Journal  of  Physiology,"  18,381,  1895. 


THE    VASOMOTOR    NERVES. 


617 


and  in  this  case  we  may  suppose  that  the  sensory  impulses  carried 
by  the  heat  nerves  inhibit  the  tone  of  the  vasoconstrictor  center 
and  cause  dilatation  or  flushing  of  the  skin.  So  far  as  man  is 
concerned,  experiments  made  with  the  plethysmograph  show  very 
clearly  that  the  vasoconstrictor  center  is  easily  affected  in  a  pressor 
or  depressor  manner  by  psychical  states  or  activities.  Mental 
work,  especially  mental  interest,  however  aroused,  is  followed  by 
a  constriction  of  the  blood-vessels  of  the  skin, — a  pressor  effect  (see 
Fig.  254) ;  and  we  may  find  an  explanation  of  the  value  of  the  reflex 
in  the  supposition  that  the  rise  of  arterial  pressure  thus  produced 


Fig.  255.— Effect  of  stimulating  the  central  end  of  the  depressor  ner^e  of  the  heart  m 
a  rabbit.  The  time  record  marks  seconds.  On  and  off  mark  the  beginning  and  end I  of 
the  stimulation.  The  blood-pressure  rises  slowly  after  the  removal  of  the  stimulus  and 
eventually  reaches  the  normal  level.  This  complete  recovery  is  not  shown  in  the  portion 


of  the  record  reproduced.     (Dawson.) 


forces  more  blood  through  the  brain  (p.  638).  On  the  other  hand, 
feelings  of  embarrassment  or  shame  may  be  associated  with  a  de- 
pressor effect,  a  dilatation  in  the  vessels  of  the  skin  manifested,  for 
example,  in  the  act  of  blushing.  In  both  cases  we  must  assume 
intracentral  nerve  paths  between  the  cortex  and  the  center  in  the 


618  CIRCULATION    OF    BLOOD    AND    LYMPH. 

medulla,  the  impulses  along  one  path  exciting  the  center,  while 
those  along  the  other  inhibit  its  tone,  or,  as  explained  below,  excite 
a  vasodilator  center.  Among  the  many  depressor  effects  that 
have  been  observed  on  stimulation  of  afferent  nerve  fibers  one  has 
aroused  especial  interest — namely,  that  caused  by  certain  afferent 
fibers  from  the  heart  or  from  the  aorta.  These  fibers  in  some 
animals — the  dog,  for  instance — run  in  the  vagus  nerve,  but  in 
other  animals,  the  rabbit,  they  form  a  separate  nerve,  the  so-called 
depressor  nerve  of  the  heart — discovered  by  Ludwig  and  Cyon 
(1866).  So  far  as  the  effect  in  question  is  concerned  the  physiolog- 
ical evidence  indicates  that  the  fibers  arise  from  the  descending 
aorta  and  it  might  be  more  appropriate  to  speak  of  them  as  the 
depressor  nerve  of  the  aorta.*  In  the  rabbit  this  nerve  forms  a 
branch  of  the  vagus,  arising  high  in  the  neck  by  two  roots,  one 
from  the  trunk  of  the  vagus  and  one  from  the  superior  laryngeal 
branch.  It  runs  toward  the  heart  in  the  sheath  with  the  vagus 
and  the  cervical  sympathetic.  The  nerve  is  entirely  afferent. 
If  it  is  cut  and  the  peripheral  end  is  stimulated  no  result  follows. 
If,  however,  the  central  end  is  stimulated  a  fall  of  blood-pressure 
occurs  and  also  perhaps  a  slowing  of  the  heart  beat  (see  Fig.  255). 
The  latter  effect  is  due  to  a  reflex  stimulation  of  the  cardio-inhib- 
itory  center  and  may  be  eliminated  by  previous  section  of  the 
vagi.  The  fall  of  blood-pressure  is  explained  by  supposing  that 
the  nerve,  when  stimulated,  inhibits,  to  a  greater  or  less  extent,  the 
tonic  activity  of  the  vasoconstrictor  center,  f  Physiological  ex- 
periments indicate  that  the  nerve  plays  an  important  regulatory 
role.t  When,  for  instance,  blood-pressure  rises  above  normal 
limits,  it  may  be  supposed  that  the  endings  of  this  nerve  in  the 
aorta  or  heart  are  stimulated  by  the  mechanical  effect,  and  the 
blood-pressure  is  thereby  lowered  by  an  inhibition  of  the  tone  of  the 
constrictor  center.  Moreover,  it  has  been  shown  by  Einthoven 
that  every  heart  beat  sends  up  this  nerve  a  series  of  nerve  impulses, 
that  is,  when  the  nerve  is  cut  and  the  ends  are  connected  with 
a  string-galvanometer,  electrical  variations  occur  synchronous 
with  the  heart  beat  (Fig.  280).  To  explain  this  result  we  can 
only  assume  that  each  heart  beat  stimulates  sensory  endings 
in  the  heart  itself  or  in  the  aorta,  and  that  the  nerve  impulses 
thus  transmitted  to  the  medulla  probably  play  a  role  in  main- 
taining the  tonic  activity  of  some  of  its  centers,  perhaps,  as 
Einthoven  suggests,  the  tonic  activity  especially  of  the  cardio- 
inhibitory  center. 

*See  Eyster  and  Hooker,  "American  Journal  of  Physiology,"  21,  373, 
1908;  also  Koster  and  Tschermak,  "Archiv  f.  die  gesammte  Physiologic," 
93,  24,  1902. 

t  See  Porter  and  Beyer,  "American  Journal  of  Physiology,"  4,  283,  1900; 
ttlso  Bayliss,  "Journal  of  Physiology,"  14,  303,  1893. 

t  Sewall  and  Steiner,  "Journal  of  Physiology,"  6,  162,  1885. 


THE    VASOMOTOR    NERVES.  619 

A  most  suggestive  example  of  the  regulating  action  of  the  depressor  nerve 
is  given  by  Sewall.  When  the  carotids  in  a  rabbit  are  clamped  a  variable 
and  not  very  large  rise  of  arterial  pressure  is  observed.  If,  however,  the 
depressor  nerves  are  first  cut,  clamping  the  carotids  causes  an  extraordinary 
rise  of  arterial  pressure.  When  the  carotids  are  closed  we  may  suppose  that 
the  resulting  anemia  of  the  medulla  stimulates  the  vasoconstrictor  center 
and  thus  tends  to  raise  arterial  pressure,  but  this  effect  is  neutralized  because 
as  the  pressure  rises  the  depressor  fibers  of  the  heart  are  stimulated.  It 
seems  evident  that  during  life  the  depressor  fibers  must  exert  a  very  important 
regulating  effect  upon  the  circulation. 

A  similar  nerve  has  been  described  anatomically  in  man,  while 
in  animals  like  the  dog,  in  which  it  is  not  present  as  a  separate 
anatomical  structure,  it  probably  exists  within  the  trunk  of  the 
vagus.  If  this  latter  nerve  is  cut  in  the  dog  and  the  central  end 
is  stimulated  a  depressor  effect  is  usually  obtained. 

Vasoconstrictor  Centers  in  the  Spinal  Cord. — From  the  description  of  the 
vasoconstrictor  mechanism  given  above  the  probable  inference  may  be  made 
that  throughout  the  thoracic  region  the  cells  of  origin  of  the  preganglionic 
fibers  may,  under  special  conditions,  act  as  subordinate  vasoconstrictor  centers 
capable  of  giving  reflexes  and  of  exhibiting  some  tonic  activity.  Numerous 
experiments  tend  to  support  this  inference  When  the  spinal  cord  is  cut^  in 
the  lower  thoracic  region  there  is  a  paralysis  of  vascular  tone  in  the  posterior 
extremities.  If,  however,  the  animal  is  kept  alive  the  vessels  gradually  re- 
cover their  tone,  although  not  connected  with  the  medullary  center.  The  re- 
sumption of  tone  in  this  case  may  be  attributed  to  the  nerve  cells  in  the  lower 
thoracic  and  upper  lumbar  region,  since  vascular  paralysis  is  again  produced 
when  this  portion  of  the  cord  is  destroyed.  Finally,  Gpltz  has  shown  that 
when  the  entire  cord  is  destroyed,  except  the  cervical  region  (p.  154),  vascular 
tone  may  be  restored  eventually  in  the  blood-vessels  affected.  In  this  case  the 
resumption  of  tonicity  must  be  referred  either  to  the  properties  of  the  muscular 
coats  of  the  arteries  themselves,  or  to  the  activity  of  the  sympathetic  nerve 
cells  that  give  rise  to  the  postganglionic  fibers.  However  this  may  be,  it  seems 
quite  clear  that  under  normal  conditions  the  great  vasoconstrictor  center  in 
the  medulla  is  the  important  seat  of  tonic  and  of  reflex  activity.  If  the  con- 
nections of  this  center  with  the  blood-vessels  are  destroyed  suddenly — for 
example,  by  cutting  the  cervical  cord — blood-pressure  falls  at  once  to  such  a 
low  level,  20  to  30  mms.  Hg.,  that  death  usually  results  unless  artificial  means 
are  employed  to  sustain  the  animal. 

Rhythmical    Activity    of    the    Vasoconstrictor    Center. — 

Throughout  life  the  vasoconstrictor  center  is  in  tone  the  intensity 
of  which  varies  with  the  intensity  and  character  of  the  reflex  im- 
pulses playing  upon  it.  Under  certain  unusual  conditions  the 
center  may  exhibit  rhythmical  variations  in  tonicity  which  make 
themselves  visible  as  rhythmical  rises  and  falls  in  the  general 
arterial  pressure  (Fig.  256),  the  waves  being  much  longer  than 
those  due  to  the  respiratory  movements.  These  waves  of  blood- 
pressure  are  observed  often  in  experiments  upon  animals,  but 
their  ultimate  cause  is  not  understood.  They  are  usually  desig- 
nated as  Traube-Hering  waves,  although  this  term,  strictly  speak- 
ing, belongs  to  waves,  synchronous  with  the  respiratory  move- 
ments, that  were  observed  by  Traube  upon  animals  in  which 
the  diaphragm  was  paralyzed  and  the  thorax  was  opened. 
These  latter  waves  are  also  due  to  a  rhythmical  action  of  the 


620  CIRCULATION   OF    BLOOD    AND    LYMPH. 

vasomotor  center.  During  sleep,  certain  much  longer,  wave-like 
variations  in  the  blood-pressure  also  occur  that  are  again  due  doubt- 
less to  a  rhythmical  change  of  tone  in  the  vasoconstrictor  center. 


Fig.  256. — Rhythmical  vasomotor  waves  of  blood-pressure  in  a  dog  (Traube-Hering 
waves).  The  upper  tracing  (1)  is  the  blood-pressure  record  as  taken  with  the  mercury 
manometer;  the  lower  tracing  (2)  is  taken  with  a  Hiirthle  manometer.  Seven  distinct 
respiratory  waves  of  blood-pressure  may  be  recognized  on  each  large  wave.  (Dawson.) 

General  Course  and  Distribution  of  the  Vasodilator  Fibers. 

— By  definition  a  vasodilator  fiber  is  an  efferent  fiber  which  when 
stimulated  causes  a  dilatation  of  the  arteries  in  the  region  supplied. 
In  searching  for  the  existence  of  such  fibers  in  the  various  nerve 
trunks  physiologists  have  used  all  the  methods  referred  to  above, — 
namely,  the  flushing  of  the  organ  as  seen  by  the  eye,  the  increased 
blood-flow,  the  increase  in  volume,  or  the  fall  in  blood-pressure  on 
the  arterial  side  associated  with  a  rise  on  the  venous  side.  By 
these  methods  vasodilator  fibers  have  been  demonstrated  in  the 
following  regions : 

1.  In  the  facial  nerve.     The  dilator  fibers  are  found  in  the  chorda  tym- 

pani  branch  and  are  distributed  to  the  salivary  glands  (submaxil- 
lary  and  sublingual)  and  to  the  anterior  two-thirds  of  the  tongue. 

2.  In  the  glossopharyngeal  nerve.     Supplies  dilator  fibers  to  the  posterior 

third  of  tongue,  tonsils,  pharynx,  parotid  gland  (tympanic  nerve). 

3.  In  the  sympathetic  chain.     In  the  cervical  portion  of  the  sympathetic 

dilator  fibers  are  carried  which  are  distributed  to  the  mucous  mem- 
brane of  the  mouth  (lips,  gums,  and  palate),  nostrils,  and  the  skin 
of  the  cheeks.  These  fibers  pass  up  the  neck  to  the  superior  cervi- 
cal ganglion  and  thence  by  communicating  branches  reach  the  Gas- 
serian  ganglion  and  are  distributed  to  the  bucco-facial  region  in  the 
branches  of  the  fifth  cranial  nerve.*  From  the  thoracic  portion  of 
the  sympathetic  vasodilator  fibers  pass  to  the  abdominal  viscera  by 
way  of  the  splanchnic  nerves  and  to  the  limbs  by  way  of  the 
branches  of  the  brachial  and  lumbar  plexuses,  but  the  data  regarding 
the  dilator  fibers  for  these  regions  are  not  as  yet  entirely  satisfactory. 
Goltz  and  others  have  shown  that  dilator  fibers  are  found  in  the 
nerves  of  the  limbs,  but  the  origin  of  these  fibers  from  the  sympa- 
thetic chain  has  not  been  demonstrated. 

*  See  "  Recherches  experimentales  sur  le  systeme  nerveux  vasomoteur, " 
Dastre  and  Morat,  1884. 


THE    VASOMOTOR    NERVES.  (521 

4.  In  the  nervi  ergentes.  Eckhard  first  gave  conclusive  proof  that  the 
erection  of  the  penis  is  essentially  a  vasodilator  phenomenon.  The 
fibers  arise  from  the  first,  second,  and  third  sacral  spinal  nerves,  pass 
to  the  hypogastric  plexus  as  the  nervi  erigentes,  and  thence  are  dis- 
tributed to  the  erectile  tissues  of  the  penis. 

The  General  Properties  of  the  Vasodilator  Nerve  Fibers. — 
Unlike  the  vasoconstrictors,  the  vasodilators  are  not  in  tonic 
activity;  at  least,  no  experimental  proof  has  been  given  that  they 
are.  In  the  case  of  the  erectile  tissue  of  the  penis  and  the  dilators 
of  the  glands  it  would  seem  that  the  fibers  are  in  activity  only 
during  the  functional  use  of  the  organ,  at  which  time  they  are 
excited  refiexly.  There  has  been  much  discussion  in  physiology  as 
to  the  nature  of  the  action  of  the  dilator  fibers.  The  muscular 
coat  of  the  small  arteries  runs  transversely  to  the  length  of  the 
vessel,  and  it  is  easy  to  see  that  when  stimulated  to  greater  con- 
traction through  the  constrictor  fibers  it  must  cause  a  narrowing 
of  the  artery.  It  is  not  so  evident  how  the  nerve  impulses  carried 
by  the  dilator  fibers  bring  about  a  widening  of  the  artery.  At 
one  time  peripheral  sympathetic  ganglia  in  the  neighborhood  of 
the  arteries  were  used  to  aid  in  the  explanation,  but,  since  histo- 
logical  evidence  of  the  existence  of  such  ganglia  is  incomplete,  the 
view  that  seems  to  meet  with  most  favor  at  present  is  as  follows: 
The  dilator  fibers  end  presumably  in  the  muscle  of  the  walls  of 
the  arteries,  and  when  stimulated  they  inhibit  the  tonic  contrac- 
tion of  this  musculature  and  thus  bring  about  a  relaxation.  These 
fibers  in  fact  inhibit  the  tonic  contraction  of  the  vascular  muscle 
just  as  the  vagus  fibers  inhibit  the  tone  of  the  cardiac  muscle. 
Dilatation  caused  by  a  vasodilator  nerve  fiber  always  presupposes, 
therefore,  a  previous  condition  of  tonic  contraction  in  the  walls 
of  the  artery,  this  tonic  condition  being  produced  either  by  the 
action  of  vasoconstrictor  fibers  or  by  the  intrinsic  properties 
of  the  muscle  itself.  In  the  nerves  of  the  limbs,  as  stated  above, 
both  vasoconstrictor  and  vasodilator  effects  may  be  detected 
by  stimulation.  It  has  been  shown  that  the  separate  fibers  may 
be  differentiated  by  certain  differences  in  properties.  Thus, 
if  the  peripheral  end  of  the  cut  sciatic  nerve  is  stimulated  by 
rapidly  repeated  induction  shocks  a  vasoconstrictor  effect  is  ob- 
tained, as  shown  plethysmographically  by  a  diminution  in  volume 
of  the  limb.  If,  however,  the  same  nerve  is  stimulated  by  slowly 
repeated  induction  shocks  the  dilator  effect  will  predominate,* 
indicating  a  greater  degree  of  irritability  on  the  part  of  these  latter 
fibers.  After  section  of  the  sciatic  nerve  the  vasodilators  degen- 
erate more  slowly  than  the  vasoconstrictors,  and  they  retain 
their  irritability  when  heated  or  cooled  for  a  longer  time  than 
the  constrictors.f 

*  Bowditch  and  Warren,  "Journal  of  Physiology,"  7,  439,  1886. 

t  Howell,  Budgett,  and  Leonard.  "Journal  of  Physiology,"  16,  298,  1894. 


622  CIRCULATION    OF   BLOOD    AND    LYMPH. 

Vasodilator  Center  and  Vasodilator  Reflexes.— Since  the 
vasodilator  fibers  form  a  system  similar  to  that  of  the  vasocon- 
strictors, it  might  be  supposed  that,  like  the  latter,  their  activity 
is  controlled  from  a  general  center,  forming  a  vasodilator  center  in 
the  brain  similar  to  the  vasoconstrictor  center.  What  evidence 
we  have,  however,  is  against  this  view.  In  the  dog  with  his  spinal 
cord  severed  in  the  lower  thoracic  region  the  penis  may  show  normal 
erection  when  the  glans  is  stimulated, — a  fact  that  indicates  a 
reflex  center  for  these  dilator  fibers  in  the  lumbar  cord.  For  the 
other  clear  cases  of  vasodilator  fibers  we  have  no  reason  at  present 
to  believe  that  they  are  ail  normally  connected  with  a  single  group 
of  nerve  cells  located  in  a  definite  part  of  the  nervous  system.  The 
dilator  fibers  in  the  facial,  glossopharyngeal,  and  cervical  sympa- 
thetic (distributed  through  the  trigeminal)  all  arise  probably  in  the 
medulla,  but  not,  so  far  as  is  known,  from  a  common  nucleus. 
Intimately  connected  with  the  question  of  the  existence  of  a  general 
vasodilator  center  is  the  possibility  of  definite  reflex  stimulation 
of  the  vasodilator  fibers.  As  stated  above,  reflex  dilatation  of  the 
blood-vessels  may  be  produced  by  stimulating  various  nerve  trunks 
containing  afferent  fibers.  The  depressor  nerve  fibers  of  the  heart 
give  only  this  effect,  and  the  sensory  fibers  from  certain  other 
regions,  notably  the  middle  ear  and  the  testis,  cause  mainly,  if  not 
exclusively,  a  fall  of  arterial  pressure  due  presumably  to  vascular 
dilatation.  The  sensory  nerves  of  the  trunk  and  limbs,  when 
stimulated  by  the  gross  methods  of  the  laboratory,  give  either 
reflex  vasoconstriction  or  reflex  vasodilatation,  and,  as  was  stated 
above,  there  is  reason  to  believe  that  these  trunks  contain  two  kinds 
of  afferent  fibers, — the  piessor  and  the  depressor.  The  action  of  the 
former  predominates  usually,  but  in  deep  anesthesia,  and  particu- 
larly in  those  conditions  of  exposure  and  exhaustion  that  precede 
the  appearance  of  "shock,"  the  depressor  effect  is  more  marked  or, 
indeed,  may  be  the  only  one  obtained.  To  explain  such  depressor 
effects  we  have  two  possible  theories.  They  may  be  due  to  reflex 
excitation  of  the  centers  giving  origin  to  the  vasodilator  fibers  or  to 
reflex  inhibition  of  the  tonic  activity  of  the  vasoconstrictor  centers. 
The  latter  explanation  is  the  one  usually  given,  especially  for  the 
typical  and  perhaps  special  effect  of  the  depressor  nerve  of  the  heart. 
This  explanation  seems  justified  by  the  general  consideration  that 
in  the  two  great  vascular  areas  through  whose  variations  in  capacity 
the  blood-flow  is  chiefly  regulated, — namely,  the  abdominal  viscera 
and  the  skin, — the  vasoconstrictor  fibers  are  chiefly  in  evidence 
and  are,  moreover,  in  constant  tonic  activity.  On  the  other  hand, 
the  fact  that  vasodilator  fibers  exist  is  presumptive  evidence  that 
they  are  stimulated  reflexly,  since  it  is  by  this  means  only  that  they 
can  normally  affect  the  blood-vessels.  Some  of  the  many  depressor 


THE    VASOMOTOR    NERVES.  623 

effects  occurring  in  the  body  must  be  due,  therefore,  to  reflex 
stimulation  of  the  dilators  and  others  to  reflex  inhibition  of  the 
constrictors.  It  would  be  convenient  to  retain  the  name  depressor 
for  the  sensory  fibers  causing  the  latter  effect,  and  to  designate 
those  of  the  former  class  by  a  different  name,  such  as  reflex  vaso- 
dilator fibers.*  Only  experimental  work  can  determine  positively 
to  which  effect  any  given  reflex  dilatation  is  due,  but  provisionally 
at  least  it  would  seem  justifiable  to  assume  that  dilatation  by  reflex 
stimulation  of  the  vasodilator  fibers  occurs  in  those  parts  of  the 
body  in  which  vasodilator  fibers  are  known  to  exist.  Thus,  the 
erection  of  the  penis  from  stimulation  of  the  glans  may  be  explained 
in  this  way,  also  the  congestion  of  the  salivary  glands  during  activity, 
the  blushing  of  the  face  from  emotions,  and  possibly  the  dilatation 
in  the  skeletal  muscles  during  contraction.  Gaskell  and  others 
have  given  reasons  for  believing  that  the  vessels  in  the  muscles  are 
supplied  with  vasodilator  nerve  fibers,  and  Kleen  f  has  shown  that 
mechanical  stimulation  of  the  muscles — kneading,  massage,  etc. — 
causes  a  fall  of  arterial  pressure. 

Vasodilatation  Due  to  Afferent  Fibers. — The  existence  of  definite  effer- 
ent vasodilator  fibers  in  the  nerve  trunks  to  the  limbs  has  been  made  doubt- 
ful by  the  work  of  Bayliss.  This  author  has  discovered  certain  facts  which  at 
present  tend  to  make  the  question  of  vasodilatation  more  obscure,  but  which, 
when  fully  understood,  will  doubtless  give  us  a  much  deeper  insight  into  the 
subject.  Briefly  stated,  he  has  shownj  that  stimulation  of  the  posterior  roots 
of  the  nerves  supplying  the  lumbo-sacral  and  the  brachial  plexus  causes  vas- 
cular dilatation  in  the  corresponding  limbs.  He  has  given  reasons  for  believing 
that  the  fibers  involved  are  afferent  fibers  from  the  limbs  and  that,  therefore, 
when  stimulated  they  must  conduct  the  impulses  in  a  direction  opposite  to 
the  normal — antidromic.  It  is  most  difficult  to  understand  how  such 
impulses,  conveyed  to  the  terminations  of  the  sensory  fibers,  can  affect  the 
muscular  tissue  of  the  blood-vessels.  It  is  most  difficult  to  understand  also 
how  such  anatomically  afferent  fibers  can  be  stimulated  reflexly  in  the  cen- 
tral nervous  system.  Some  light  has  been  thrown  upon  this  subject  by  recent 
work§  upon  the  vascular  dilatation  of  the  conjunctival  membrane  when 
irritated  locally  by  substances,  such  as  oil  of  mustard,  that  cause  inflammation. 
It  has  been  found  that  the  vascular  dilatation  in  these  cases  is  not  due  to  a 
direct  effect  of  the  irritant  on  the  vessels,  and  that  it  is  not  a  reflex  effect 
through  the  spinal  cord  or  the  posterior  root  ganglia.  On  the  other  hand,  the 
effect  is  not  obtained  if  the  terminations  of  the  sensory  fibers  of  the  region  are 
anesthetized,  or  if  the  sensory  nerves  to  the  region  are  cut  and  time  is  allowed 
for  them  to  degenerate.  The  hypothesis  used  to  explain  the  reaction  is  that  the 
sensory  fibers  to  the  region  branch  at  their  termination,  one  branch  going  to 
the  sensory  ending,  the  other  to  the  blood-vessels.  When,  therefore,  the  sen- 
sory ending  is  stimulated  there  is  a  local  reflex,  of  the  nature  of  an  axon-reflex, 
through  the  other  limb  of  the  bifurcation,  which  effects  a  dilatation  of  the 
blood-vessel.  If  this  explanation  holds  upon  further  examination,  it  will 
establish  the  existence  of  a  peripheral  mechanism  for  the  production  of  local 
vasodilatation  which  has  not  been  taken  into  account  heretofore  (see  p.  152). 

*  See  Hunt,  "Journal  of  Physiology,"  18,  381,  1895. 
t  Kleen,  "Skandinavisches  Archiv  f.  Physiologic,"  247,  1887. 
t  Bayliss,  "Journal  of  Physiology,"  26,  173,  1900,  and  28,  276,  1902. 
§  Ninian  Bruce,  "Quarterly  Journal  of  Exp.  Physiology,"  6,  339,  1913; 
also  Bardy,  "Skandinavisches  Archiv  f.  Physiologic,"  32,  198,  1914. 


624 


CIRCULATION    OF    BLOOD    AND    LYMPH. 


General   Schema. — The  main  facts  regarding  the  vasomotor 
apparatus  may  be  summarized  briefly  in  tabular  form  as  follows: 


Efferent       vasomotor 
nerve  fibers. 


Afferent  fibers   giving 
vasomotor  reflexes. 


I.  Vasoconstrictor  fibers — distributed  mainly  to 
the  skin  and  the  abdominal  viscera  (splanch- 
nic area),  all  connected  with  a  general  center 
in  the  medulla  oblongata,  and  in  constant 
tonic  activity. 

II.  Vasodilator  fibers — distributed  especially  to 
the  erectile  tissue,  glands,  bucco-f  acial  region, 
and  muscles;  not  connected  with  a  general 
center  and  not  in  tonic  activity. 

I.  Pressor  fibers.  Cause  vascular  constriction  and 
rise  of  arterial  pressure  from  reflex  stimula- 
tion of  the  vasoconstrictor  center — e.  g.t 
sensory  nerves  of  skin. 

II.  Depressor  fibers.  Cause  vascular  dilatation  and 
fall  of  arterial  pressure  from  reflex  inhibition 
of  the  tonic  activity  of  the  vasoconstrictor 
center, — e.  g.t  depressor  nerve  of  heart. 
III.  Depressor  (or  reflex  vasodilator)  fibers.  Cause 
vascular  dilatation  and  fall  of  arterial  pres- 
sure from  stimulation  of  the  vasodilator 
center, — e.  g.,  erectile  tissue,  congestion  of 
glands  in  functional  activity. 

It  may  be  supposed  that  under  normal  conditions  the  activity 
of  this  mechanism  is  adjusted  so  as  to  control  the  blood-flow  through 
the  different  organs  in  proportion  to  their  needs.  When  the  blood- 
vessels of  a  given  organ  are  constricted  the  flow  through  that  organ 
is  diminished,  while  that  through  the  rest  of  the  body  is  increased 
to  a  greater  or  less  extent  corresponding  to  the  size  of  the  area  in- 
volved in  the  constriction.  When  the  blood-vessels  of  a  given 
organ  are  dilated  the  blood-flow  through  that  organ  is  increased  and 
that  through  the  rest  of  the  body  diminished  more  or  less.  The 
adaptability  of  the  vascular  system  is  wonderfully  complete,  and 
is  worked  out  mainly  through  the  reflex  activity  of  the  nervous 
system  exerted  partly  through  the  vasomotor  fibers  and  partly 
through  the  regulatory  nerves  of  the  heart. 

Regulation  of  the  Blood-supply  by  Chemical  and  Mechan- 
ical Stimuli. — From  time  to  time  attention  has  been  called  to 
the  fact  that  the  calibre  of  the  blood-vessels  may  be  influenced 
otherwise  than  through  the  agency  of  vasoconstrictor  and  vaso- 
dilator nerve  fibers.  Gaskell,  for  example,  has  shown  that  acids 
in  slight  concentration  cause  a  vascular  dilatation.  Bayliss  *  has 
generalized  the  facts  of  this  kind,  and  has  suggested  that  in  addi- 
tion to  the  nervous  regulation  described  in  the  preceding  pages 
there  may  be  formed  chemical  substances  of  a  definite  character 
which  exert  a  similar  useful  regulating  action.  As  examples  of 


Bayliss  in  "Ergebnisse  der  Physiologic,"  1906,  v.,  319. 


THE  VASOMOTOR  NERVES.  625 

this  influence,  we  have  the  lactic  acid  produced  in  muscles  during 
activity  and  probably  also  the  carbon  dioxid  produced  in  this  as 
in  other  tissues.  These  substances  in  physiological  concentra- 
tions cause  a  relaxation  of  muscular  tonus  by  virtue  of  their  acidity 
and,  therefore,  may  act  to  produce  a  local  dilatation  during  func- 
tional activity  and  thus  provide  the  organ  with  more  blood  at  the 
time  that  it  is  needed.  On  the  other  hand,  the  internal  secretion 
of  the  adrenal  glands  (epinephrin)  and  possibly  also  of  the  infun- 
dibular portion  of  the  pituitary  gland  have  the  reverse  effect, 
causing  a  vasoconstriction  and  *thus  tending  to  maintain  normal 
vascular  tone.  Evidence  has  accumulated  in  recent  years  which 
indicates  that  the  secretion  of  epinephrin  may  be  increased  under 
various  conditions,  such  as  emotional  excitement*  or  sensory 
stimulation,  and  it  is  possible  that  by  this  means  the  arterial 
pressure  may  be  increased  under  conditions  which  in  nature 
might  be  supposed  to  call  for  mental  and  muscular  activity. 
Therapeutically,  various  substances  may  be  introduced  into  the 
circulation  which,  by  chemical  action,  cause  a  constriction  or  a 
dilatation  of  the  peripheral  arteries  and  thus  raise  or  lower  general 
blood-pressure.  In  the  former  class  of  vasoconstricting  reagents 
we  have  such  substances  as  epinephrin,  digitalis,  etc.,  while  in  the 
latter  class  the  nitrites,  especially  amyl  nitrite  (Brunton),  have 
been  much  used,  particularly  in  such  conditions  as  angina  pectoris, 
in  which  a  quick  relief  from  a  state  of  vascular  hypertension  is 
desirable. 

*  Cannon,  "Bodily  Changes  in  Pain,  Hunger,  Fear,  and  Rage,"  1915. 
40 


CHAPTER  XXXIII. 

THE  VASOMOTOR  SUPPLY  OF  THE  DIFFERENT 
ORGANS. 

There  are  three  important  organs  of  the  body — namely,  the 
heart,  the  lungs,  and  the  brain — in  which  the  existence  of  a  vaso- 
motor  supply  is  still  a  matter  of  uncertainty.  A  very  great  deal 
of  investigation  has  been  attempted  with  reference  to  these  organs, 
but  the  technical  difficulties  in  each  case  are  such  that  no  entirely 
satisfactory  conclusion  has  been  reached.  A  brief  review  of  some 
of  the  experimental  work  on  record  will  suffice  to  make  evident  the 
present  condition  of  our  knowledge. 

Vasomotors  of  the  Heart. — The  coronary  vessels  lie  in  or  on 
the  musculature  of  the  heart.  Any  variation  in  the  force  of  con- 
traction or  tonicity  of  the  heart  muscle  itself  will  therefore  affect 
possibly  the  caliber  of  the  arterioles  and  the  rate  of  blood-flow  in  the 
coronary  system.  At  each  contraction  of  the  ventricles  the  coro- 
nary circulation  is  probably  interrupted  by  a  compression  of  the 
smaller  arteries  and  veins,  and  the  size  of  these  vessels  during  dias- 
tole will  naturally  vary  with  the  extent  of  relaxation  of  the  cardiac 
muscle.  Since  stimulation  of  either  of  the  efferent  nerves  supplying 
the  heart,  vagus  and  sympathetic,  affects  the  condition  of  the  mus- 
culature, it  is  evident  at  once  how  difficult  it  is  to  distinguish  a 
simultaneous  effect  upon  the  coronary  arteries,  if  any  such  exists. 
Newell  Martin*  found  that  stimulation  of  the  vagus  causes  dilata- 
tion of  the  small  arteries  on  the  surface  of  the  heart  as  seen  through 
a  hand  lens.  Moreover,  when  the  heart  is  exposed  and  artificial 
respiration  is  stopped  the  arteries  may  be  seen  to  dilate  before 
the  asphyxia  causes  any  general  rise  of  arterial  pressure.  Martin 
interpreted  these  observations  to  mean  that  the  coronary  arteries 
receive  vasodilator  fibers  through  the  vagus.  Porterf  measured 
the  outflow  through  the  coronary  veins  in  an  isolated  cat's  heart 
kept  alive  by  feeding  it  with  blood  through  the  coronary  arteries. 
He  found  that  this  outflow  is  diminished  when  the  vagus  nerve 
is  stimulated,  and  hence  concluded  that  the  vagus  carries  vasocon- 
strictor fibers  to  the  heart.  Maasf  reports  similar  results  also 
obtained  from  cats'  hearts  kept  alive  by  an  artificial  circulation 
through  the  coronary  arteries.  Stimulation  of  the  vagus  slowed 

*  Martin,  "  Transactions  Medical  and  Chirurgical  Faculty  of  Maryland." 
1891. 

t  Porter,  "  Boston  Medical  and  Surgical  Journal, "  January  9,  1896. 
j  Maas,  "  Archiv  f.  die  gesammte  Physiologic, "  74,  281,  1899. 

626 


VASOMOTOR    SUPPLY    OF   THE    ORGANS.  627 

the  stream  (vasoconstrictor  fibers),  while  stimulation  of.  the 
sympathetic  path  quickened  the  flow  (vasodilator  fibers).  Neither 
Maas  nor  Porter  gives  conclusive  proof  that  the  heart  musculature 
was  not  affected  by  the  stimulation.  Wiggers  reports*  that  the 
effect  of  epinephrin  upon  a  heart  perfused  through  the  coronary 
arteries,  but  not  beating,  is  to  decrease  the  flow,  while  upon  the 
beating  heart  this  effect  is  reversed,  owing  to  the  action  of  the 
epinephrin  upon  the  heart  contractions.  Schaefer,f  on  the  con- 
trary, gets  entirely  opposite  results.  When  an  artificial  circula- 
tion was  maintained  through  {he  coronary  system  and  the  amount 
of  outflow  was  determined,  he  found  that  this  quantity  was  not 
definitely  influenced  by  stimulation  of  either  the  sympathetic  or 
the  vagus  branches.  Moreover,  injection  of  epinephrin  into  the 
coronary  circulation  had  no  influence  upon  the  outflow,  and  since 
this  substance  causes  an  extreme  constriction  in  the  vessels  of 
organs  provided  with  vasoconstrictor  fibers,  the  author  concludes 
that  the  coronary  arteries  have  no  vasomotor  nerve  fibers.  Lang- 
endorff  reports  that  strips  of  coronary  artery  suspended  in  an  epi- 
nephrin solution  exhibit  relaxation  instead  of  the  contraction  shown 
by  other  arteries,  and  this  fact,  if  corroborated,  might  be  considered 
as  evidence  for  the  presence  of  vasodilator  fibers.  It  is  evident 
from  a  consideration  of  these  results  that  the  existence  of  vasomotor 
fibers  to  the  heart  vessels  is  still  a  matter  open  to  investigation. 

Vasomotors  of  the  Pulmonary  Arteries. — The  pulmonary 
circulation  is  complete  in  itself,  and  it  differs  from  the  systemic  cir- 
culation chiefly  in  that  the  peripheral  resistance  in  the  capillary 
area  is  much  smaller.  Consequently  the  arterial  pressure  in  the 
pulmonary  artery  is  small,  while  the  velocity  of  the  blood-flow  is 
greater  than  in  the  systemic  circuit, — that  is,  a  larger  portion  of 
the  energy  of  the  contraction  of  the  right  ventricle  is  used  in  mov- 
ing the  blood.  From  the  mechanical  conditions  present,  it  is  ob- 
vious that  the  pressure  in  the  pulmonary  artery  might  be  increased 
by  a  vasoconstriction  of  the  smaller  lung  arteries,  or,  on  the  other 
hand,  by  an  increase  in  the  blood-flow  to  the  right  ventricle  through 
the  venae  cavse,  or,  lastly,  by  back  pressure  from  the  left  auricle  when 
the  left  ventricle  is  not  emptying  itself  as  well  as  usual  on  account 
of  high  aortic  pressure.  While  it  is  comparatively  easy,  therefore, 
to  measure  the  pressure  in  the  pulmonary  artery,  it  is  difficult,  in 
the  interpretation  of  the  changes  that  occur,  to  exclude  the  possi- 
bility of  the  effects  being  due  indirectly  to  the  systemic  circula- 
tion. Bradford  and  Dean,J  by  comparing  carefully  the  simul- 
taneous records  of  the  pressures  in  the  aorta  and  a  branch  of  the 
pulmonary  artery,  came  to  the  conclusion  that  the  latter  may 

*  Wiggers,  "American  Journal  of  Physiology,"  1909.  Proceedings  of 
the  American  Physiological  Society. 

f  "Archives  des  sciences  biologiques,"  11,  suppl.  volume,  251,  1905. 
J  Bradford  and  Dean,  "Journal  of  Physiology,"  16,  34,  1894. 


628  CIRCULATION    OF    BLOOD    AND    LYMPH. 

be  affected  independently  by  stimulation  of  the  third,  fourth, 
and  fifth  thoracic  spinal  nerves,  and  hence  concluded  that 
these  nerves  contain  vasoconstrictor  fibers  to  the  pulmonary 
vessels,  the  course  of  the  fibers  being,  in  general,  that  taken 
by  the  accelerator  fibers  to  the  heart,  namely,  to  the  first 
thoracic  sympathetic  ganglion  by  the  rami  communicantes  and 
thence  to  the  pulmonary  plexus.  They  give  evidence  to  show 
that  these  fibers  are  stimulated  during  asphyxia.  The  authors 
state,  however,  that  the  effects  obtained  upon  the  pressure  in  the 
pulmonary  artery  are  relatively  and  absolutely  small  as  compared 
with  the  vasomotor  effects  in  the  aortic  system.  Similar  results 
have  been  obtained  by  other  observers  ( Franc.  ois-Franck).  Using 
another  and  more  direct  method,  Brodie  and  Dixon*  have  come 
to  an  opposite  conclusion.  These  authors  maintained  an  artificial 
circulation  through  the  lungs  and  measured  the  rate  of  outflow 
when  the  nerves  supplying  the  lungs  were  stimulated.  Under  these 
conditions  stimulation  of  the  vagus  or  the  sympathetic  caused  no 
definite  change  in  the  rate  of  flow, — a  result  which  would  indicate 
that  neither  nerve  conveys  vasomotor  fibers  to  the  lung  vessels. 
This  conclusion  was  strengthened  by  the  fact  that  in  similar  per- 
fusions  made  upon  other  organs  (intestines)  .vasomotor  effects  were 
easily  demonstrated.  Moreover,  epinephrin,  pilocarpin,  and  mus- 
carin  cause  marked  vasoconstriction  when  irrigated  through  the 
intestine,  but  have  no  such  effect  upon  the  vessels  in  the  lungs. 
These  authors  conclude  that  the  lung  vessels  have  no  vasomotor 
nerves  at  all,  and  their  experimental  evidence  might  be  accepted 
as  satisfactory  except  for  the  fact  that  a  similar  method  in  the 
hands  of  another  observer  has  given  opposite  results.  Plumierf 
finds  that  the  outflow  through  a  perfused  lung  is  diminished  in 
some  cases  by  stimulation  of  the  sympathetic  branches  to  the  lungs, 
and  also  by  the  use  of  epinephrin.  Under  such  conditions  it  is 
necessary  to  defer  a  decision  until  more  experiments  are  reported. 
Regarding  the  vasomotors  of  the  lungs,  one  can  only  say,  as  in  the 
case  of  the  heart,  that  their  existence  has  not  been  demonstrated. 

The  Circulation  in  the  Brain  and  Its  Regulation. — The 
question  of  the  existence  of  vasomotor  nerves  to  the  brain  brings 
up  necessarily  the  larger  question  of  the  special  characteristics  of 
the  cranial  circulation.  The  brain  is  contained  in  a  rigid  box  so 
that  its  free  expansion  or  contraction  with  variations  in  the  amount 
of  blood  can  not  take  place  as  in  other  organs  and  we  have  to  con- 
sider in  how  far  this  fact  modifies  its  circulation. 

The  Arterial  Supply  of  the  Brain. — The  brain  is  supplied  through 
the  two  internal  carotids  and  the  two  vertebrals,  which  together 
form  the  circle  of  Willis.  It  will  be  remembered  also  that  the 

*  Brodie  and  Dixon,  "Journal  of  Physiology,"  30,  476,  1904. 
fPlumier,  "Journal  de  physiologic  et  de  pathologic  generate,"  6,  665, 
1904;  see  also  Wiggers,  "Jour,  of  Pharmacol.  and  Exper.  Therap.,"  1,  341, 1909. 


VASOMOTOR  SUPPLY  OF  THE  ORGANS.  629 

vertebral  arteries  give  off  the  posterior  and  the  anterior  spinal  arte- 
ries, which  supply  the  spinal  cord,  and  that  the  last-named  artery 
makes  anastomoses  along  the  cord  with  the  intercostal  arteries 
and  other  branches  from  the  descending  aorta.  From  the  ana- 
tomical arrangement  alone  it  is  evident  that  the  circulation  in  the 
brain  is  very  well  protected  from  the  possibility  of  being  inter- 
rupted by  the  accidental  closure  of  one  or  more  of  its  arteries.  In 
some  animals,  the  dog,  one  can  ligate  both  internal  carotids  and 
both  vertebrals  without  causing  unconsciousness  or  the  death  of  the 
animal.  In  an  animal  under  these  conditions  a  collateral  circula- 
tion must  be  brought  into  play  through  the  anastomoses  of  the 
spinal  arteries.  In  man,  on  the  contrary,  it  is  stated  that  ligation 
of  both  carotids  is  dangerous  or  fatal. 

The  Venoics  Supply.  —The  venous  system  of  the  brain  is  peculiar, 
especially  in  the  matter  of  the  venous  sinuses.  These  large  spaces 
are  contained  between  folds  of  the  dura  mater  or,  on  the  base  of 
the  skull,  between  the  dura  mater  and  the  bone.  The  channel 
hollowed  out  in  the  bone  is  covered  with  a  roof  of  tough,  inex- 
tensible  dura  mater,  and  indeed  in  some  animals  the  basal  sinuses 


Cerebrum. 

Fig.  257.— Diagram  to  represent  the  relations  of  the  meningeal  membranes  of  the  cere- 
brum, the  position  of  the  subarachnoidal  space  and  of  the  venous  sinuses. 

may  in  part  be  entirely  incased  in  bone.  The  larger  cerebral  veins 
open  into  these  sinuses;  the  openings  have  no  valves,  but,  on  the 
contrary,  are  kept  patent  and  protected  from  closure  by  the  struc- 
ture of  the  dura  mater  around  the  orifice.  The  sinuses  receive 
blood  also  from  the  veins  of  the  pia  mater,  dura  mater,  and  from 
the  bones  of  the  skull  through  the  diploic  veins.  The  venous  blood 
emerges  from  the  skull  in  man  mainly  through  the  opening  of  the 
lateral  sinuses  into  the  internal  jugular  vein,  although  there  is  also 
a  communication  in  the  orbit  between  the  cavernous  sinus  and  the 
ophthalmic  veins  through  which  the  cranial  blood  may  pass  into 
the  system  of  facial  veins  or  vice  versa,  another  communication 
with  the  venous  plexuses  of  the  cord,  and  a  number  of  small  emis- 
sary veins.  In  some  of  the  lower  animals — the  dog,  for  instance — 
ihe  main  outflow  is  into  the  external  jugular  through  what  is  known 


630 


CIRCULATION    OF    BLOOD    AND    LYMPH. 


as  the  superior  cerebral  vein.  A  point  of  physiological  interest  is 
that  the  venous  sinuses  and  their  points  of  emergence  from  the  skull 
are  by  their  structure  well  protected  from  closure  by  compression. 
The  Meningeal  Spaces  and  Cerebrospinal  Liquid. — The  general 
arrangement  of  the  meningeal  membranes,  and  particularly  of  the 
meningeal  spaces,  is  important  in  connection  with  the  mechanics  of 
the  brain  circulation.  In  the  skull  the  dura  mater  adheres  to  the  bone, 
the  pia  mater  invests  closely  the  surface  of  the  brain,  while  between 
lies  the  arachnoid  (Fig.  257).  The  capillary  space  between  the  arach- 
noid and  the  dura,-  the  so-called  subdural  space,  may  be  neglected. 
Between  the  arachnoid  and  the  pia  mater,  however,  lies  the  sub- 

arachnoidal  space  more  or 
less  intersected  by  septa  of 
connective  tissue,  but  in  free 
communication  throughout 
the  brain  and  cord.  This 
subarachnoidal  space  is  filled 
with  a  liquid,  the  cerebro- 
spinal  liquid,  which  forms  a 
pad  inclosing  the  brain  and 
cord  on  all  sides.  The  liquid 
surrounding  the  cord  is  in 
free  communication  with 
that  in  the  brain,  as  is  indi- 
cated in  the  accompanying 
schematic  figure  (Fig.  258). 
Within  the  brain  itself  there 
are  certain  points  at  fhe  an- 
gles and  hollows  of  the  differ- 
ent parts  of  the  brain  at  which 
the  subarachnoidal  space 
is  much  enlarged,  forming 
the  so-called  cisternse,  which 
are  in  communication  one 
with  another  by  means  of  the 
less  conspicuous  canals  (see 
Fig.  259) .  The  whole  system 
is  also  in  direct  communica- 
tion with  the  ventricles  of 
the  brain  on  the  one  hand,  through  the  foramen  of  Magendie, 
the  foramina  of  Luschka,  and  perhaps  at  other  places,  and,  on  the 
other  hand,  along  the  cranial  and  spinal  nerves  it  is  continued 
outward  in  the  tissue  spaces  of  the  sheaths  of  these  nerves.  The 
Pacchionian  bodies  constitute  also  a  peculiar  feature  of  the  sub- 
arachnoidal space.  These  bodies  occur  in  numbers  that  vary 
with  the  individual  and  with  age,  and  are  found  along  the  sinuses, 


—Cerebro  -Spinal  LiptucL 
jjfiinal  Cord. 


Fig,  258. — Diagram  to  show  the  connec- 
tion of  the  subarachnoidal  space  in  the  brain 
and  the  cord. 


VASOMOTOR  SUPPLY  OF  THE  ORGANS. 


631 


especially  the  superior  longitudinal  sinus.  Each  body  is  a  minute, 
pear-shaped  protrusion  of  the  arachnoidal  membrane  into  the  inte- 
rior of  a  sinus,  as  represented  schematically  in  Fig.  260.  Through 
these  bodies  the  cerebrospinal 
liquid  is  brought  into  close 
contact  with  the  venous 
blood,  the  two  being  sepa- 
rated only  by  a  thin  layer 
of  dura  and  the  very  thin 
arachnoid.  The  number  of 
the  Pacchionian  bodies  is 
hardly  sufficient  to  lead  us 
to  suppose  that  they  have  a 
special  physiological  impor- 
tance. The  cerebrospinal  liq- 
uid found  in  the  subarach- 
noidal  space  and  the  ventri- 
cles of  the  brain  is  a  very 
thin,  watery  liquid  having  a 
specific  gravity  of  only  1.007 
to  1.008.  It  contains  only 
traces  of  proteins  and  other 
organic  substances,  which  may  vary  under  pathological  condi- 
tions. It  is  thinner  and  more  watery  than  the  lymph,  resembling 
rather  the  aqueous  humor  of  the  eye.  The  amount  of  this  fluid 


Fig.  259. — Diagram  to  show  the  location 
of  the  cisternse  and  canals  of  the  subarach- 
noidal  space. — (Poirier  and  Charpy.) 


Fig.  260.— Schema  to  show  the  relations  of  the  Pacchionian  bodies  to  the  sinuses: 
d,  d,  Folds  of  the  dura  mater,  inclosing  a  sinus  between  them;  v.b.,  the  blood  in  the 
sinus;  a,  the  arachnoidal  membrane;  p,  the  pia  mater;  Pa.,  the  Pacchionian  body  as 
a  projection  of  the  arachnoid  into  the  blood  sinus. 

present  normally  is  difficult  to  determine.  Various  figures  have 
been  given,  but  it  is  usually  stated  to  amount  to  60  to  80  c.c.  If 
these  figures  are  correct  it  evidently  does  not  form  a  thick  envelope 
to  the  nervous  system.  Under  abnormal  conditions  (hydroceph- 


632 


CIRCULATION    OF    BLOOD    AND    LYMPH. 


alus,  etc.)  the  quantity  may  be  greatly  increased,  and  it  is  stated 
that  normally  'the  amount  increases  with  age,  after  puberty,  as 
the  brain  shrinks  in  size.*  It  is  physiologically  interesting  to  find 
that  this  liquid  may  be  formed  very  promptly  from  the  blood  and, 
when  in  excess,  be  absorbed  quickly  by  the  blood.  In  fractures 
of  the  base  of  the  skull,  for  instance,  the  liquid  has  been  observed 
to  drain  off  steadily  at  the  rate  of  200  c.c.  or  more  per  day.  On  the 
other  hand,  when  one  injects  physiological  saline,  into  the  sub- 
arachnoidal  space  under  some  pressure  it  is  absorbed  with  sur- 
prising rapidity.  After  death,  also,  the  liquid  present  in  the  sub- 
arachnoidal  space  is  soon  absorbed.  Experimental  work  f  indicates 
that  the  cerebrospinal  liquid  is  formed  within  the  ventricles  from 

the  choroid  plexuses,  and,  in- 
deed, there  is  some  evidence 
that  its  formation  may  be  due 
to  a  process  of  active  secretion 
on  the  part  of  the  epithelial 
cells  covering  these  plexuses. 
However  that  may  be,  the 
stream  of  liquid  starts  within 
the  ventricles  and  passes  out 
through  the  foramen  of  Ma- 
gendie  and  the  foramina  of 
Luschka  into  the  subarach- 
noidal  spaces,  from  which  in 
turn  it  is  absorbed  into  the 
cerebral  veins  (Fig.  260a).  If 
the  aqueduct  of  Sylvius  or  the 
foramina  of  exit  are  blocked, 
the  continued  formation  of 
liquid  within  the  ventricles 
may  lead  to  the  production  of 
internal  hydrocephalus.  The  rapidity  of  formation  of  the  secre- 
tion is  increased  apparently  by  pituitary  extracts  and  diminished 
by  thyroid  extracts,  t 

Intracranial  Pressure. — By  intracranial  pressure  is  meant  the 
pressure  in  the  space  between  the  skull  and  the  brain, — therefore 
the  pressure  in  the  subarachnoidal  liquid  and  presumably  also  the 
pressure  in  the  ventricles  of  the  brain,  since  the  two  spaces  are  in 
communication.  This  pressure  may  be  measured  by  boring  a  hole 
through  the  skull,  dividing  the  dura,  and  connecting  the  under- 
lying space  with  a  manometer.  Most  observers  who  have  measured 


Fig.  260a.— Diagram  by  Dandy  and  Black- 
faa,  slightly  changed,  to  show  the  circulation  of 
the  cerebrospinal  liquid:  I,  II,  lateral  ventri- 
cles; III,  the  third  ventricle;  IV,  the  fourth 
ventricle;  A,  foramina  of  Monroe;  L,  L,  foram- 
ina of  Luschka;  M,  foramen  of  Magendie;  S, 
aqueduct  of  Sylvius.  The  arrows  show  the  direc- 
tion of  flow  of  the  cerebrospinal  liquid. 


Stillman,  "Archives  of  Internal  Medicine,"  8,  193,  1911. 


1913 


also  Frazier  and  Peet,  ibid.,  36,  464,  1915. 


VASOMOTOR    SUPPLY    OF    THE    ORGANS. 


633 


this  pressure  state  that  it  is  the  same  as  the  venous  pressure  within 
the  sinuses.  This  we  can' understand  when  we  remember  the  close 
relations  between  the  subarachnoidal  liquid  and  the  large  veins 
and  sinuses.  We  may  consider  that  the  large  veins  are  surrounded 
by  the  cerebrospinal  liquid,  and  consequently  an  equilibrium  of 
pressure  may  be  established  between  them;  any  rise  in  the  intra- 
cranial  pressure  raises  venous  pressure  by  compression  of  the 
veins,  and  probably  by  accelerating  the  flow  of  liquid  from  the 
Subarachnoidal  space  into  the  venous  circulation.  On  the  other 
hand,  an  increase  in  venous  pressure  might  be  assumed  to  cause 
a  corresponding  rise  in  intracranial  pressure  due  to  the  compression 
following  the  expansion  of  the  venous  walls,  and  to  the  retardation 
of  the  inflow  of  cerebrospinal  liquid  into  the  veins.  If  the  cerebro- 
spinal liquid  is  formed  in  the  choroid  plexuses  by  a  process  of 
secretion  there  may  be,  of  course,  a  secretion  pressure  not  depend- 
ent on  the  mechanical  conditions  in  the  vascular  circulation,  which 
may  cause  independent  variations  in  the  pressure  within  the  sub- 
arachnoidal space.  But  it  is 
not  at  all  certain  that  the 
cerebrospinal  liquid  is  formed 
by  a  process  of  active  secre- 
tion, and  in  any  event  the 
changes  in  mechanical  press- 
ure within  the  cerebral  veins 
must  influence  directly  the 
pressure  in  the  surrounding 
cerebrospinal  liquid,  and  vice 
versa  in  the  way  described 
above.  Compression  of  the 
veins  of  the  neck  raises  the 
pressure  in  the  cerebral  veins 
and  also  intracranial  pressure, 
and  a  higher  general  arterial 
pressure  also  results  finally  in 
a  higher  pressure  in  the  cere- 
bral veins,  and,  therefore,  in 
the  subarachnoidal  space. 
Under  pathological  condi- 
tionsrf  such  as  tumors,  ab- 
scesses, excessive  formation  of 
cerebrospinal  liquid,  etc., 
which  lead  to  a  general  com- 
pression of  the  brain,  intra- 
cranial pressure  may  be  in- 
creased beyond  normal  limits.  Experimental  investigations  show 
that  so  long  as  the  intracranial  pressure  remains  below  that  of  the 


I 

V 

Fig.  261.— Schema  to  represent  the 
transmission  of  arterial  pressure  through 
the  brain  substance  to  the  veins:  A,  The 
artery,  V,  the  vein,  represented  as  entering 
into  and  emerging  from  a  box  with  rigid 
walls  and  filled  with  incompressible  liquid; 
c,  c,  the  intervening  area  of  small  arte- 
ries, etc.  An  expansion  of  the  walls  of 
the  arterial  system  by  the  pulse  wave  or  by 
a  rise  of  arterial  pressure  increases  the  pres- 
sure on  the  surrounding  liquid  and  this  is 
transmitted  through  the  liquid  to  the  walls 
of  the  veins  and  compresses  them,  since  at 
this  point  of  the  circuit  the  intravascular 
pressure  is  low. 


634  CIRCULATION    OF    BLOOD    AND    LYMPH. 

arteries  supplying  the  brain  the  circulation  through  the  brain  is 
not  markedly  affected.  If,  however,  the  intracranial  pressure  rises 
above  general  arterial  pressure  the  flow  through  the  substance  of 
the  brain  is  prevented  and  a  condition  of  anemia  results  which 
would  presumably  cause  unconsciousness.  In  anesthetized  ani- 
mals submitted  to  such  a  condition  it  has  been  shown  that  a 
compensation  takes  place;  the  anemic  condition  of  the  medulla 
stimulates  the  cardio-inhibitory  center,  causing  a  slower  heart 
beat;  at  the  same  time  it  stimulates  also  the  vascmotor  center, 
causing  a  general  vasoconstriction  in  the  rest  of  the  body,  the 
result  of  which  is  to  raise  the  arterial  pressure  and  reestablish  the 
cranial  circulation  (Gushing).* 

Reduced  to  its  simplest  form,  the  normal  conditions  may  be  represented 
by  a  schema  such  as  is  given  in  Fig.  261.  A  system  with  an  artery,  capillary 
area,  and  a  vein  is  represented  as  inclosed  in  a  rigid  box  and  surrounded  by 
an  incompressible  liquid.  According  to  the  conditions  prevailing  in  the  body, 
the  pressure  in  the  interior  of  A  and  its  branches  is  much  higher  than  in  V. 
If,  now,  the  pressure  in  A  is  increased  the  greater  pressure  brought  to  bear  on 
the  walls  will  tend  to  expand  them;  a  greater  pressure  will  thereby  be  com- 
municated to  the  outside  liquid,  which,  in  turn,  will  compress  the  veins  cor- 
respondingly. The  expansion  on  the  arterial  side  is  made  possible  by  a  corre- 
sponding diminution  on  the  venous  side  where  the  internal  pressure  is  least. 

The  recorded  measurements  of  the  intracranial  pressure  show 
that  it  may  vary  from  50  to  60  mms.  of  mercury,  obtained  during 
the  great  rise  of  pressure  following  strychnin  poisoning,  to  zero 
or  less,  as  obtained  by  Hillf  from  a  man  while  in  the  erect  pos- 
ture. In  this  position  the  negative  influence  of  gravity  is  at  its 
maximum. 

The  Effect  of  Variations  in  Arterial  Pressure  upon  the  Blood- 
flow  through  the  Brain. — Quite  a  number  of  observers!  have  proved 
experimentally  that  a  rise  of  general  pressure  is  followed  not  only 
by  an  increase  in  the  intracranial  tension,  but  also  by  an  increased 
blood-flow  through  the  brain.  There  has  been  much  discussion  as 
to  whether  a  rise  of  arterial  pressure  in  the  basilar  arteries  can  cause 
any  actual  increase  in  the  amount  of  blood  in  the  brain  or  whether 
it  expresses  itself  solely  or  mainly  as  an  increased  amount  of  flow. 
In  the  other  organs  of  the  body,  except  perhaps  the  bones,  a  general 
rise  of  pressure,  not  accompanied  by  a  constriction  of  the  organ's 
own  arteries,  causes  a  dilatation  or  congestion  of  the  organ  together 
with  an  increased  blood-flow.  Physiologically  the  congestion — 
that  is,  the  increased  capacity  of  the  vessels — is  of  no  value;  the 

*  Gushing,  "American  Journal  of  the  Medical  Sciences,"  1902  and  1903, 
and  also  Eyster,  Burrows  and  Essick,  "Journal  of  Experimental  Medicine," 
11,  489,  1909. 

t  Bayliss  and  Hill,  "Journal  of  Physiology,"  18,  356,  1895. 

•*•  See  Gartner  and  Wagner,  "Weiner  med.  Wochenschrift,"  1887;  de  Boeck 
and  Verhorgen,  "Journal  de  Me"decine,  etc.,"  Brussels;  Roy  and  Sherrington, 
"Journal  of  Physiology,"  11,  85,  1890;  Reiner  and  Schnitzler,  "Archiv  f.  exp. 
Pathol.  u.  Pharmakol.,"  3§,  249,  1897. 


VASOMOTOR    SUPPLY    OF    THE    ORGANS.  635 

important  thing  is  the  increase  in  the  quantity  of  blood  flowing 
through.  In  the  brain,  owing  to  the  peculiarities  of  its  position, 
it  has  been  suggested  that  perhaps  no  actual  increase  in  size  is 
possible.  It  is  evident,  however,  that  the  existence  of  the  liquid 
in  the  subarachnoidal  space  makes  possible  some  actual  expan- 
sion of  the  organ.  For  as  the  pressure  upon  this  liquid  increases  it 
may  be  driven  into  the  dural  sac  of  the  cord  (Fig.  258)  and  along  the 
sheaths  of  the  cranial  and  spinal  nerves.  To  what  extent  this  is 
actually  possible  in  man  we  do  not  know,  nor  do  we  know  how  much 
cerebrospinal  liquid  is  contained  in  the  skull  and  brain  of  man.  In 
the  dog  Hill  *  finds  experimentally  that  the  brain  can  expand  only 
by  an  amount  equal  to  2  or  3  c.c.  without  causing  a  rise  of  intra- 
cranial  tension ;  so  that  probably  these  figures  represent  the  amount 
of  expansion  possible  in  this  animal  by  simple  squeezing  out  of  the 
cerebrospinal  liquid.  If  the  rise  of  arterial  pressure  is  such  as  to 
expand  the  brain  beyond  this  point,  then  it  may  not  only  force 
out  cerebrospinal  liquid,  if  any  remains,  but,  as  explained  in  the 
last  paragraph,  it  will  compress  the  veins  and  raise  intracranial 
pressure.  To  the  extent  that  the  veins  are  compressed  as  the  ar- 
teries expand  no  actual  increase  in  the  size  or  blood-capacity  of  the 
brain  takes  place.  That  an  expansion  of  the  brain  arteries  com- 
presses the  veins  is  indicated  very  clearly  by  the  normal  occurrence 
of  a  venous  pulse  in  this  organ.  The  blood  flows  out  of  the  veins  of 
the  brain  in  pulses  synchronous  with  the  arterial  pulses,  and  this 
venous  pulse  may  be  recorded  easily  as  shown  in  Fig.  262.  In  this 
case  the  sudden  expansion  of  the  arteries  compresses  the  cerebral 
veins,  giving  a  synchronous  rise  of  pressure  in  the  interior  of  the 
sinuses.  Some  authors  (Geigel,  Grashey),  on  purely  theoretical 


Fig.  262. — Simultaneous  record  of  pulse  in  the  circle  of  Willis  (c)  and  in  the  toreu- 
lar  Herophili  (<).  The  tracing  from  the  circle  of  Willis  was  obtained  by  means  of  a 
Hurthle  manometer  connected  with  the  head  end  of  the  internal  carotid.  It  will  be  noted 
that  the  pulses  are  simultaneous,  indicating  that  the  venous  pulse  is  due  to  the  transmis- 
sion of  the  arterial  pulse  through  the  brain  substance. 

grounds,  have  held  that  this  compression  of  the  veins  in  cases  of  an 
extensive  rise  in  arterial  pressure  may  result  in  a  diminished 
blood-flow  through  the  organ, — a  sort  of  self-strangulation  of 
its  own  circulation.  Actual  experiment  shows  that  this  is  not  the 
case.  Any  ordinary  rise  of  general  arterial  pressure  is  accompanied 

*  Hill,  "The  Physiology  and  Pathology  of  the  Cerebral  Circulation," 
London,  1896. 


636  CIRCULATION    OF    BLOOD    AND    LYMPH. 

by  a  greater  blood-flow  through  the  brain,  so  long  as  the  arterial 
pressure  remains  above  intracranial  pressure.  Whether  the  brain 
increases  in  volume  as  a  result  of  a  rise  of  arterial  pressure  is,  on  the 
physiological  side,  unimportant;  the  main  point  is  that  the  amount 
of  blood  flowing  through  it  is  increased  under  such  circumstances  as 
would  cause  a  like  result  in  other  organs.  That  the  compression  of 
the  veins  does  not  produce  any  sensible  obstruction  to  the  blood- 
flow  may  be  understood  easily.  In  the  first  place,  this  compression 
does  not  take  place  at  the  narrow  exit  from  the  skull, — since  at  that 
point  the  sinuses  are  protected  from  the  action  of  intracranial  press- 
ure. The  compression  takes  place  doubtless  upon  the  cerebral  veins 
emptying  into  the  sinuses,  and  at  this  point  the  venous  bed, 
taken  as  a  whole,  is  so  large  that  the  expansion  due  to  an 
ordinary  rise  of  arterial  pressure  is  distributed  and  has  but  little 
effect  on  the  volume  of  the  flow.  Secondly,  very  great  increases  in 
arterial  pressure,  up  to  the  point  of  rupture  of  the  walls,  have  less 
and  less  effect  in  actually  expanding  the  arteries ;  a  point  is  reached 
eventually  at  which  these  tubes  become  practically  rigid,  so  that 
farther  expansion  is  impossible.  This,  of  course,  is  true  for  every' 
organ. 

The  Regulation  of  the  Brain  Circulation. — It  is  still  a  matter 
of  uncertainty  whether  the  arteries  of  the  brain  possess  vasomotor 
nerves.  Most  of  the  authors  who  have  studied  the  matter  experi- 
mentally have  concluded  that  there  are  none.*  These  authors  were 
unable  to  show  that  stimulation  of  any  of  the  nerve  paths  that 
might  innervate  the  brain  vessels  causes  local  effects  upon  the  brain 
circulation.  Whenever  such  stimulations  caused  a  change  in  pres- 
sure or  amount  of  flow  in  the  brain  the  result  was  referable  to  an  alter- 
ation of  general  arterial  pressure  produced  by  a  vasomotor  change 
elsewhere  in  the  body.  When  as  a  result  of  such  stimulation  the 
pressure  rises  in  the  circle  of  Willis,  one  may  infer  that  if  this  is  due 
to  a  local  constriction  in  the  cerebral  arterioles  there  should  be  a 
fall  of  pressure  in  the  venous  sinuses  and  a  diminished  flow  of  blood; 
if,  on  the  contrary,  it  is  due  to  a  constriction  elsewhere  in  the  body 
that  has  increased  general  arterial  pressure,  but  has  not  constricted 
the  brain  circuit,  then  there  should  be  a  rise  in  venous  pressure  and 
intracranial  pressure,  together  with  a  greater  flow  of  blood  through 
the  brain.  Most  observers  obtain  this  latter  result.  Some  inves- 
tigators, Hiirthle,  Francois-Franck,  and  others,  f  on  the  other 
hand,  have  obtained  results,  especially  from  stimulation  of  the 
cervical  sympathetic,  which  indicated  local  vasoconstriction  or  vaso- 
dilatation  in  the  brain.  So  far  as  the  experimental  results  for  or 

*  See  Roy  and  Sherrington,  Bayliss  and  Hill,  Hill,  Gaertner  and  Wagner, 
loc.  cit.,  and  Hill  and  MacLeod,  "Journal  of  Physiology,"  26,  394,  1901. 


t  Hiirthle,  "Archiv  f.  die  gesammte  Physiologic,"  44,  574,  1889;  Fran^ois- 
Franck,  "Archives  de  physiol.  normale  et  pathologique "  1890;  Weber 
"Archiv  f.  Physiologic,"  1908,  457. 


VASOMOTOR    SUPPLY   OF    THE    ORGANS.  637 

against  vasomotors  are  based  upon  a  determination  of  the  amount 
of  flow  through  the  brain  or  upon  measurements  of  pressure  within 
the  circle  of  Willis,  it  has  been  shown  that  an  undetermined  fac- 
tor is  involved  which  makes  such  observations  unsatisfactory. 
It  has  been  shown  *  in  experiments  upon  dogs  that  when  the  intra- 
cranial  pressure  is  raised  so  high  as  to  obliterate  the  circulation 
through  the  brain  substance  itself  an  abundant  circulation  may  be 
maintained  through  the  skull  by  perfusion  into  the  internal  carotid 
—that  is  to  say,  there  are  paths  between  the  circle  of  Willis  and  the 
emergent  veins  other  than  the  capillary  circulation  through  the 
brain  substance.  One  such  path  is  furnished  by  an  anastomosis 
at  the  base  of  the  skull  between  the  circle  (through  the  internal 
carotid)  and  the  ophthalmic  branch  of  the  internal  maxillary  artery. 
It  might,  therefore,  very  well  happen  that  the  circulation  in  the  brain 
substance  may  be  changed  without  materially  affecting  the  amount 
of  blood-flow  from  the  brain,  owing  to  the  fact  that  these  other 
paths  are  open.  Weber,  who  used  the  plethysmographic  method 
of  measuring  the  volume  of  the  brain,  states  positively  that  stimu- 
lation of  the  cervical  sympathetics,  of  the  cortical  surface,  and  of 
various  sensory  nerves  gives  in  animals  such  changes  in  brain 
volume  as  can  only  be  interpreted  by  the  assumption  that  the  brain 
vessels  possess  both  vasoconstrictor  and  vasodilator  nerve-fibers. 
Since  these  reactions  can  be  obtained  reflexly  after  destruction  of 
the  general  vasomotor  center  in  the  medulla,  he  is  forced  to  assume 
a  special  vasomotor  center  for  the  brain  lying  further  forward  than 
the  medulla,  a  conclusion  which  is  not  entirely  satisfactory. 
Plethysmographic  observations  on  the  brain  during  sleep,  as 
reported  by  some  observers  (p.  269),  have  also  been  inter- 
preted as  indicating  the  presence  of  a  local  vasomotor  apparatus. 
An  argument  of  a  different  kind  in  favor  of  vasomotor  fibers  has 
been  submitted  by  Wiggers.j  In  experiments  made  upon  an  iso- 
lated brain  (in  the  skull)  perfused  with  an  artificial  circulation,  he 
states  that  addition  of  epinephrin  caused  a  diminution  in  the  out- 
flow from  the  organ,  thus  showing  that  the  epinephrin  had  caused  a 
constriction  somewhere  in  the'circuit.  If,  as  some  authors  believe, 
epinephrin  acts  only  on  plain  muscle  that  is  innervated  by  sympa- 
thetic nerve-fibers,  this  result  furnishes  indirect  evidence  for  the  ex- 
istence of  such  fibers  in  the  case  of  the  brain  vessels.  Using  the 
same  method,  this  author  states  that  electrical  stimulation  applied 
directly  to  the  sheath  of  the  internal  carotid  at  its  entrance  into 
the  skull  also  causes  a  decrease  in  the  outflow,  a  fact  which  would 
indicate  the  existence  of  constrictor  fibers  running  in  the  sheath 
of  this  artery.  On  the  whole,  it  will  be  seen  that  the  evidence  for 


1908. 


*  Eyster,  Burrows,  and  Essick,  ''Journal  of  Exp.  Medicine/'  u,  489,  1909. 
f  Wiggers,  "American  Journal  of  Physiology,"  14,  452,  1905;  and  21,  454, 


638  CIRCULATION    OF    BLOOD    AND    LYMPH. 

the  existence  of  a  vasomotor  regulation  of  the  brain  circulation  is 
not  conclusive.  If  vasomotors  are  present  it  is  possible  that  they 
may  serve  to  control  the  distribution  of  blood  within  the  cerebral 
area,  while  the  general  supply  to  the  brain  as  a  whole  is  increased  or 
decreased  by  a  mechanism  of  another  sort  described  by  Roy  and 
Sherrington.  According  to  these  authors  the  blood-flow  through 
the  brain  is  controlled  indirectly  by  vasomotor  effects  upon  the  rest 
of  the  body.  When,  for  example,  a  vasoconstriction  occurs 
in  the  skin  or  the  splanchnic  area  the  result  is  a  rise  of  pressure 
in  the  aorta,  and,  therefore,  a  rise  of  pressure  in  the  circle  of  Willis, 
which  then  forces  more  blood  through  the  brain.  Adopting  this 
view,  we  can  understand  the  teleology  of  certain  well-known  vaso- 
motor reflexes.  Stimulation  of  the  skin  generally  causes  a  reflex 
constriction  and  rise  of  pressure,  and  one  can  well  understand  that 
this  result  is  valuable  if  it  means  a  greater  flow  of  blood  through 
the  brain,  since  under  the  conditions  of  nature  such  stimulation, 
especially  when  painful,  demands  alertness  and  increased  activity 
on  the  part  of  the  animal.  Attention  has  also  been  called  to  the 
fact  that  in  plethysmographic  observations  on  man  the  most 
certain  and  extensive  constrictions  of  the  skin  vessels  are  those 
caused  by  increased  mental  activity,  especially  when  it  takes 
the  form  of  emotional  excitement.  Mosso  has  shown  by  observa- 
tions upon  men  wrth  trephine  holes  in  the  skull  that  the  constriction 
of  the  limbs  is  always  accompanied  by  a  dilatation  of  the  brain. 
This  fact,  therefore,  fits  exactly  the  view  that  is  being  considered. 
The  peripheral  constriction,  by  raising  general  blood-pressure,  di- 
lates the  brain  more  or  less,  and,  what  is  more  important,  drives 
more  blood  through  it.  It  is  difficult  to  understand  why  psychical 
activity  is  associated  in  this  way  with  a  peripheral  constriction, 
and  usually  an  increased  heart-rate,  unless  the  object  of  the  reflex 
is  to  increase  the  blood-supply  to  the  brain.  Even  if  vasomotor 
fibers  are  subsequently  shown  to  be  present  in  the  brain,  the  im- 
portance of  this  reflex  in  providing  a  greater  flow  to  the  central 
organ  at  the  time  that  it  is  in  activity  may  still  be  admitted.  A 
general  irrigation,  so  to  speak,  is*  provided  for  by  this  means. 
Local  vasomotors  may  be  used  to  divert  this  flow  mainly  through 
one  or  another  cerebral  area. 

Vasomotor  Nerves  of  the  Head  Region. — The  vasomotor 
supply  of  the  various  parts  of  the  head,  including  the  mouth  cavity, 
has  been  investigated  by  many  observers.  It  would  appear  from 
the  results  of  most  of  these  investigations  that  the  vasoconstrictor 
supply  for  the  skin,  including  the  ears,  the  eye,  the  mouth,  and 
buccal  glands,  is  derived  mainly,  if  not  entirely,  from  the  sympa- 
thetic nervous  system.  These  fibers  arise  from  the  spinal  cord  in  the 
upper  thoracic  nerves,  first  to  the  fifth  or  sixth,  emerge  by  the  rami 
communicantes  to  the  sympathetic  chain,  in  which  they  pass  upward 


VASOMOTOR    SUPPLY    OF    THE    ORGANS.  639 

and  end,  for  the  most  part,  in  the  superior  cervical  ganglion.  From 
this  ganglion  they  are  distributed,  by  various  routes,  as  postgan- 
glionic  fibers.  In  one  interesting  instance  the  constrictor  fibers 
for  the  head  were  supposed  to  take  a  somewhat  different  course. 
It  was  shown  by  Schiff,  long  ago,  that  in  the  rabbit  the  ear  receives 
vasomotor  fibers  from  the  auricularis  magnus  nerve,  a  branch  of  the 
third  cervical  nerve.  Later  investigations  indicate  (Meltzer)  that 
the  ear,  in  fact,  receives  most  of  its  vasoconstrictor  fibers  by  this 
route.  Fletcher,  however,  has  shown  that  these  fibers  do  not  emerge 
from  the  brain  in  the  roots  of  the  third  cervical,  but  rather  in  the 
general  outflow  from  the  thoracic  region.  After  reaching  the  sym- 
pathetic chain  these  particular  fibers  pass  to  the  third  cervical  by 
the  gray  rami  from  the  first  thoracic  ganglion,  which  communicate 
with  a  number  of  the  cervical  nerves.  On  the  other  hand,  the 
vasodilator  fibers  for  the  head  are  supplied  in  part  by  way  of  the 
cervical  sympathetic,  following  the  same  general  path  as  the  con- 
strictors, and  in  part  by  way  of  the  cranial  nerves  (seventh,  ninth) 
and  the  sympathetic  ganglia  with  which  they  connect.  According 
to  Langley,  the  outflow  of  the  seventh  nerve  passes  to  the  spheno- 
palatine  ganglion,  whence  as  postganglionic  fibers  they  accompany 
the  branches  of  the  superior  maxillary  nerve  and  cause  vasodila- 
tation  in  the  membrane  of  the  nose,  soft  palate,  tonsils,  uvula,  roof 
of  mouth,  upper  lips,  gums,  and  pharynx.  The  well-known  dilators 
of  the  submaxillary  and  sublingual  glands  are  contained  in  the 
chorda  tympani  branch  of  the  seventh  nerve;  the  preganglionic 
fibers  terminate  probably  in  the  small  peripheral  ganglia  connected 
with  these  glands.  The  fibers  that  emerge  in  the  ninth  pass  in 
part  directly  to  the  tongue  and  in  part  terminate  first  in  the  otic 
ganglion,  whence  they  are  distributed  with  the  branches  of  the 
inferior  maxillary  to  the  lower  lips,  cheeks,  gums,  and  parotid  and 
orbital  glands.  Dastre  and  Morat  describe  the  vasodilators  in  the 
cervical  sympathetic  as  reaching  the  fifth  cranial  nerve  by  com- 
municating branches  from  the  superior  cervical  ganglion  and  state 
that  they  cause  dilatation  of  the  bucco-facial  region, — that  is, 
the  lips,  the  gums,  cheeks,  palate,  nasal  mucous  membrane,  and 
the  corresponding  skin  areas. 

The  Trunk  and  the  Limbs. — The  vasoconstrictor  fibers  for 
these  regions  are  distributed,  so  far  as  is  known,  chiefly  to  the  skin. 
They  are  all  derived  immediately  from  the  sympathetic  chain  and 
ultimately  from  the  outflow  in  the  anterior  roots  of  the  thoracic 
and  lumbar  spinal  nerves.  Those  for  the  upper  limbs  arise  from 
the  midthoracic  region  chiefly  (fourth  to  ninth  thoracic  nerves), 
those  for  the  lower  limbs  arise  in  the  nerves  of  the  lower  thoracic 
and  upper  lumbar  region  (eleventh,  twelfth,  thirteenth  thoracic 
[dog]  and  first  and  second  lumbar).  The  vasodilator  fibers  in  the 
nerves  of  the  limbs  have  been  demonstrated  frequently,  as  already 


640  CIRCULATION    OF    BLOOD    AND    LYMPH. 

explained.  Whether  or  not  these  fibers  also  pass  through  .the 
sympathetic  system,  following  the  same  general  course  as  the 
vaso  constrictors,  has  not  been  shown  conclusively.  The  most 
definite  work  at  present  (Bayliss)  indicates  that  the  vasodilator 
effect  is  directly  caused  in  some  unknown  way  by  afferent  fibers 
in  the  nerves  forming  the  brachial  and  the  sciatic  plexus.  The 
theoretical  explanations  offered  for  this  result  have  been  referred 
to  (p.  623). 

The  Abdominal  Organs.— The  stomach  and  intestines  receive 
their  most  important  supply  of  vasoconstrictor  fibers  by  way  of  the 
splanchnic  nerves  and  celiac  ganglion.  These  fibers  emerge  from 
the  cord  in  the  lower  thoracic  spinal  nerves,  from  the  fifth  down, 
and  the  upper  lumbar  nerves,  and  they  supply  the  whole  mesenteric 
circulation  as  far  as  the  descending  colon.  The  stomach  and  in- 
testines are  said  to  receive  vasoconstrictor  fibers  from  the  vagus 
nerve  also  (Lohmann).  According  to  some  observers  (Franyois- 
Franck  and  Hallion),  the  mesenteric  vessels  receive  a  supply  of 
vasodilator  fibers  by  way  of  the  splanchnics,  and  it  is  also  stated 
that  similar  fibers  reach  this  region  through  the  vagus  nerve. 
The  pancreas  has  been  shown  to  receive  vasoconstrictor  fibers  by 
way  of  the  splanchnics,  and  the  kidney,  according  to  Bradford, 
receives  vasodilator  as  well  as  vasoconstrictor  fibers  from  the  same 
nerve.  Most  of  the  vasomotor  fibers  to  the  kidney  of  the  dog 
emerge  from  the  cord  in  the  roots  of  the  eleventh,  twelfth,  and 
thirteenth  thoracic  nerves,  and  those  for  the  liver  (Franyois- 
Franck  and  Hallion)  come  from  about  the  same  region.  The 
vasoconstrictors  to  the  spleen  are  said  to  leave  the  spinal  cord 
chiefly  in  the  anterior  roots  of  the  sixth,  seventh,  and  eighth 
thoracic  nerves. 

The  Genital  Organs. — Both  vasoconstrictor  and  vasodilator 
fibers  have  been  discovered  for  the  external  genital  organs  (penis, 
scrotum,  clitoris,  vulva).  The  vasoconstrictors  arise  in  the  dog 
from  the  thirteenth  thoracic  to  the  fourth  lumbar  nerves,  pass  over 
to  the  sympathetic  chain,  and  thence  reach  the  organs  either  by 
way  of  the  hypogastric  nerve  and  pelvic  plexus  or  by  way  of  the 
sacral  sympathetic  ganglia  and  their  branches  to  the  pudic  nerves. 
The  vasodilator  fibers  arise  from  the  sacral  spinal  nerve,  being  the 
best  known  of  the  sacral  autonomic  system.  They  enter  the  ner- 
vus  erigens  and  thence  reach  the  organs  by  way  of  the  pelvic 
plexus.  The  especial  importance  of  these  fibers  in  the  process  of 
erection  is  described  in  the  section  on  the  physiology  of  the  repro- 
ductive organs.  The  internal  genital  organs — uterus,  vagina, 
vas  deferens,  seminal  vesicles,  etc. — receive  no  vasomotor  fibers 
from  the  sacral  autonomic  system, — that  is,  from  the  nervi  erigentes 
— but  do  receive  a  supply  of  constrictor  fibers  from  the  sympathetic 
system.  These  latter  fibers  emerge  from  the  cord  in  the  roots  of 


VASOMOTOR  SUPPLY  OF  THE  ORGANS.  641 

the  upper  lumbar  nerves  and  reach  the  organs  by  way  of  the  in- 
ferior mesenteric  ganglion  and  hypogastric  nerve.* 

Vasomotor  Supply  of  the  Skeletal  Muscles. — Gaskell  f  es- 
pecially has  given  evidence  of  the  existence  of  vasomotor  fibers  in 
the  muscles.  He  concludes,  as  the  result  of  his  work,  that  the  blood- 
vessels of  the  muscles  receive  both  vasoconstrictor  and  vasodilator 
fibers,  but  that  the  latter  greatly  predominate, — at  least,  their 
physiological  effect  is  much  more  evident  in  experimental  work. 
As  proof  of  the  presence  of  dilator  fibers  he  gives  such  results  as 
these:  The  mylohyoid  muscle  of  the  frog  is  thin  enough  to  be 
observed  directly  under  the  microscope.  When  curarized  and 
stimulated  through  its  motor  nerve  the  small  vessels  may  be  seen 
to  dilate  and  there  is  an  augmented  flow  of  blood.  In  a  dog  section 
of  the  motor  nerve  to  a  muscle  is  followed  by  a  greatly  increased 
flow  of  blood,  which,  however,  is  only  temporary  and  is  referable  to 
a  mechanical  stimulation  of  the  dilator  fibers.  Direct  stimulation 
of  the  severed  nerve  causes  an  increased  flow  of  blood  through  the 
muscles,  but  if  the  muscles  are  first  completely  curarized  stimulation 
causes,  on  the  contrary,  a  decreased  flow.  This  last  result  is  ex- 
plained on  the  supposition  that  curare  paralyzes  the  endings  of  the 
dilator  fibers  and  thus  allows  the  effects  of  the  constrictors  to  mani- 
fest themselves.  Since,  however,  Bayliss  has  given  evidence  to 
show  (p.  623)  that  the  dilator  effect  in  the  limbs  is  due  to  the  anti- 
dromic  action  of  afferent  fibers,  it  is  evident  that  this  important 
question  needs  reinvestigation.  Various  physiologists  have  shown 
that  muscular  activity  is  accompanied  by  an  increase  in  the  blood- 
flow  through  the  muscle,  as  we  should  expect,  but  it  remains  uncer- 
tain whether  this  result  is  brought  about  solely  by  an  increased 
activity  of  the  heart  or  by  the  combined  effect  of  vasodilatation  and 
increase  in  heart-work.  Kaufmann  J  takes  this  latter  view  in  con- 
sequence of  some  interesting  results  obtained  upon  horses.  He 
measured  the  blood-flow  through  the  masseter  muscle  and  the 
elevator  of  the  lip  in  a  horse  in  which  the  muscles  were  exercised 
normally  by  the  act  of  eating.  The  blood-flow  was  increased  as 
much  as  five  times  over  that  observed  during  rest,  and  that  this 
increase  was  due  in  part  at  least  to  a  local  dilatation  seems  to  be 
proved  by  the  fact  that  the  blood-pressure  in  the  artery  supplying 
the  muscle  fell,  while  that  in  the  vein  rose.  While,  therefore,  our 
experimental  knowledge  of  the  vasomotors  of  the  muscles  needs 
further  investigation,  we  may  provisionally  accept  the  view  ad- 
vocated by  Gaskell, — namely,  that  the  vasomotor  supply  to  the 

*  For  the  bibliography  of  the  vasomotor  supply  to  the  various  organs  see 
Langley,  "Ergebnisse  der  Physiologic,"  vol.  ii.,  part  n.,  p.  820,  1903. 

t  Gaskell,  "Journal  of  Physiology/'  1,  262,  1878-79. 

j  Kaufmann,  "Archives  de  physiologic  normale  et  pathologique,"  J1892, 
pp.  279  and  495. 
41 


642  CIRCULATION    OF    BLOOD    AND    LYMPH. 

muscles  consists  essentially  of  dilator  fibers  and  that  these  fibers 
are  brought  into  action  reflexly  whenever  the  muscles  contract, 
thus  providing  an  increased  blood-flow  in  proportion  to  the  func- 
tional activity.  It  should  be  added  that  the  local  dilatation  in 
the  muscles  during  activity  may  be  due  also  to  the  chemical  action 
of  the  (acid)  metabolic  products  on  the  blood-vessels  (p.  624). 

The  Vasomotor  Nerves  to  the  Veins. — It  is  assumed  in  physi- 
ology that  the  vasoconstrictors  and  vasodilators  end  in  the  muscula- 
ture of  the  small  arteries.  The  veins  also  have  a  muscular  coat, 
and  it  is  possible  that  if  this  musculature  were  innervated  from 
the  central  nervous  system  we  should  have  another  efficient  factor 
in  controlling  the  blood-flow.  Mall  has  given  very  clear  proof  that 
the  portal  vein  receives  vasoconstrictor  fibers  from  the  splanchnic 
nerve,*  but  this  supply  may  be  exceptional,  as  the  portal  system 
itself  is  unique.  The  portal  vein,  indeed,  plays  the  role  physiolog- 
ically of  an  artery  in  regard  to  the  liver.  Roy  and  Sherringtonf 
give  some  evidence  for  the  existence  of  venomotor  nerves  to  the 
large  veins  of  the  neck,  and  Thompson,  as  also  Bancroft, J  reports 
experiments  in  which  it  was  found  that  stimulation  of  the  sciatic 
nerve  caused  a  visible  constriction  of  the  superficial  veins  of  the 
hind  limbs.  Finally,  it  has  been  shown  that  solutions  of  epinephrin 
cause  contraction  in  rings  of  vein  as  they  do  in  arterial  strips. 
On  the  accepted  explanation  of  the  way  in  which  epinephrin  acts 
this  fact  implies  that  the  muscle  in  the  veins  is  supplied  by  sympa- 
thetic autonomic  nerve-fibers.  If  such  a  system  exists  it  must 
exert  an  important  influence  upon  the  supply  of  blood  to  the 
heart.! 

THE  CIRCULATION  OF  THE  LYMPH.. 

The  direction  of  flow  of  the  lymph  is  from  the  tissues  toward  the  large 
lymphatic  trunks,  the  thoracic  and  the  right  lymphatic  duct.  The  flow  is 
maintained  in  this  direction  mainly  by  a  difference  in  pressure  at  the  two  ends. 
At  the  opening  of  the  large  trunks  into  the  jugular  veins  the  pressure  is  very 
low;  in  the  vein,  in  fact,  it  may  be  zero  or  even  negative  as  compared  with 
the  atmospheric  pressure.  The  opening  between  the  lymph  vessel  and 
the  vein  is  protected  by  a  valve  which  opens  toward  the  vein,  and  the  lymph, 
therefore,  will  flow  into  the  vein  as  long  as  the  pressure  in  the  latter  is  lower 
than  that  in  the  lymphatic  duct.  At  the  other  extremity  of  the  system, 
in  the  tissue  spaces  to  which  the  lymphatic  capillaries  are  distributed,  the 
pressure,  on  the  contrary,  is  high.  Its  exact  amount  is  not  known, 
but,  since  the  pressure  in  the  blood  capillaries  is  equal  to  40-60  mms.  Hg, 
the  pressure  in  the  liquid  of  the  surrounding  tissues  must  also  be  consider- 
able. The  tissues  are,  in  fact,  in  a  condition  .of  turgidity  owing  to  the 
pressure  of  the  lymph  in  the  tissue-spaces.  This  difference  in  pressure 
at  the  two  ends  of  the  lymphatic  system  is  the  main  constant  factor  in  mov- 
ing the  lymnh.  It  is  obvious  that  in  the  long  run  it  is  dependent  upon  the 
pressure  within  the  blood-vessels  and  therefore  upon  the  force  of  the  heart 

*  Mall,  "Archiv  f.  Physiologic,"  p.  409,  1892. 

t  Roy  and  Sherrington,  "Journal  of  Physiology,"  11,  85,  1890. 

J  Bancroft,  "American  Journal  of  Physiology,"  1,  477,  1898. 

§  See  Henderson,  "American  Journal  of  Physiology,"  23,  345,  1909. 


VASOMOTOR    SUPPLY    OF    THE    ORGANS.  643 

beat.  The  contractions  of  the  heart  supply  the  energy,  not  only  for  the  move- 
ment of  the  blood,  but  also  for  the  much  slower  movement  of  the  lymph.  The 
circulation  of  the  lymph  is  aided,  however,  by  many  accessory  factors.  In 
some  animals  there  "are  genuine  lymph  hearts  upon  the  course  of  the  vessels, — 
that  is,  pulsatile  expansions  of  the  lymph  vessels  whose  force  of  beat,  con- 
trolled by  valves,  is  directly  applied  to  moving  the  lymph.  No  such  structures 
are  found  in  the  mammalia,  but  according  to  some  observers  the  large  re- 
ceptacle at  the  beginning  of  the  thoracic  duct,  receptaculum  chyli  may 
undergo  contractions,  and  is,  besides,  under  the  influence  of  motor  and 
inhibitory  nerves.  Such  movements,  if  they  occur,  must  be  equivalent  to  the 
action  of  a  lymph  heart  in  their  influence  upon  the  flow  of  lymph.  The 
flow  of  lymph  or  chyle  in  the  intestinal  area  is  also,  without  doubt,  greatly 
assisted  by  the  peristaltic  and  especially  by  the  rhythmic  contractions  of  the 
musculature  of  the  intestines,  and  by  the  independent  movements  of  the 
villi.  The  volume  of  the  lymph  in  this  region  is  especially  large  and  the 
lymph  capillaries  and  veins  are  provided  with  valves.  Rhythmical  con- 
tractions of  the  musculature  of  the  intestine  must  squeeze  the  lymph  toward 
the  thoracic  duct,  acting  like  a  local  pump  to  accelerate  the  flow  of  lymph. 
A  similar  influence  is  exerted  by  the  contractions  of  the  skeletal  muscles.  The 
compression  exerted  by  the  shortened  fibers  squeezes  the  lymph  vessels  and, 
on  account  of  the  valves  present,  forces  the  lymph  onward  toward  the  larger 
ducts.  The  flow  of  lymph  from  the  resting  muscles — the  arms  and  legs,  for 
instance-^is  normally  small  in  quantity,  but  during  muscular  exercise  and 
massage  it  is  obviously  increased.  This  increase  may  be  observed  in  experi- 
mental work  by  placing  a  cannula  in  the  thoracic  duct.  Active  or  passive 
movements  of  the  limbs  under  these  conditions  will  cause  a  noticeable  increase 
in  the  outflow  from  the  duct.  Still  another  factor  which  exercises  an  in- 
fluence upon  the  flow  of  the  lymph  is  found  in  the  respiratory  movements  of 
the  thorax.  At  each  inspiration  the  pressure  within  the  thorax  is  dimin- 
ished (increase  of  negative  pressure),  and  this  factor  influences  the  lymph 
flow  in  several  ways :  By  increasing  the  flow  of  blood  through  the  large  veins 
at  the  edge  of  the  thorax,  jugulars,  and  subclavians.,  it  doubtless  aspirates 
lymph  from  the  thoracic  and  right  lymphatic  ducts  into  these  veins.  More- 
over, by  lowering  the  pressure  upon  the  intrathoracic  portion  of  the  thoracic 
duct  it  also  aspirates  the  lymph  from  the  abdominal  portion  of  this  vessel. 

When  we  place  a  cannula  in  the  thoracic  duct  and  measure  the  outflow 
directly  it  is  found  to  be  exceedingly  slow  and  variable.  Older  measure- 
ments (Weiss)  indicate  that  it  has  a  velocity  in  the  duct  in  the  neck  of  about 
4  mms.  per  second,  but  this  velocity  changes  naturally  with  the  conditions 
influencing  the  production  of  lymph  in  the  tissues.  After  meals,  during  the 
period  of  absorption  from  the  alimentary  canal,  the  flow  is  much  more  abun- 
dant than  in  the  fasting  animal.  Heidenhain  estimates  that  for  a  dog  weighing 
10  kgms.  the  total  outflow  from  the  thoracic  duct  in  twenty-four  hours  is  equal 
to  640  c.c.  Munk  and  Rosenstein,  from  observations  upon  a  case  with  a 
lymph,  fistula,  estimated  that  in  man  the  flow  may  be  equal  to  50  to  100  or  120 
c.c.  per  hour. 


SECTION  VI. 
PHYSIOLOGY  OF  RESPIRATION. 

Historical. — The  term  respiration  as  usually  employed  in 
physiology  refers  to  the  process  of  gaseous  exchange  between  an 
organism  and  its  environment.  This  exchange  consists  essentially 
in  the  absorption  of  oxygen  by  the  living  matter  and  the  elimination 
of  carbon  dioxid.  It  is  one  of  the  generalizations  of  physiology  that 
all  living  things,  with  the  exception  perhaps  of  the  anaerobic 
organisms,  require  oxygen  for  their  vital  processes — that  is,  for 
the  normal  course  of  those  chemical  changes  in  the  tissue  cells 
which  we  group  under  the  general  term  of  metabolism.  On  the 
other  hand,  one  of  the  universal  end-products  of  this  metabolism 
is  carbon  dioxid.  Hence,  respiration  in  some  form  is  one 
great  characteristic  of  living  things.  In  the  simplest  animals 
and  plants,  the  unicellular  organisms,  the  exchange  between 
the  air  (or  water)  and  the  organism  takes  place  directly,  but 
in  the  more  complex  animals  some  form  of  respiratory  appara- 
tus is  developed  whose  function  consists  either  in  bringing 
the  air  or  oxygen-laden  water  to  the  constituent  cells,  as  in  the  air 
tubes  of  the  insects,  or  in  bringing  the  circulating  blood  into  contact 
with  the  air  or  water,  as  in  the  case  of  animals  provided  with  lungs 
or  gills.  In  man  and  the  air-breathing  vertebrates  the  latter  device 
is  employed  and  one  may  distinguish  in  such  animals  between 
internal  and  external  respiration.  By  the  latter  term  is  meant  the 
gaseous  exchange,  absorption  of  oxygen  and  elimination  of  carbon 
dioxid,  that  takes  place  in  the  lungs  between  the  blood  in  the  pul- 
monary capillaries  and  the  air  in  the  alveoli.  By  internal  respira- 
tion is  meant  the  similar  exchange  that  takes  place  in  the  systemic 
capillaries  between  the  blood  and  the  tissue  elements.  All  of  this 
exchange  is,  so  to  speak,  secondary,  since  the  essential  process 
consists  in  the  history  of  the  oxygen  after  it  is  absorbed  into  the 
tissues, — that  is,  the  part  taken  by  the  oxygen  in  the  metabolism  of 
living  matter.  This  process,  however,  is  a  part  of  the  subject  of 
nutrition.  The  food  absorbed  from  the  digestive  organs  and  the 
oxygen  taken  from  the  blood  have  a  common  history,  or  at  least 
their  reactions  are  indissolubly  connected  after  they  come  within 
the  field  of  influence  of  the  living  molecules.  This  side  of  the  func- 
tion of  the  oxygen  may  be  considered,  therefore,  more  appropriately 
in  the  seption  on  nutrition.  In  the  present  section  attention  will  be 
directed  to  the  beautiful  means  that  have  been  adapted  to  the  pur- 

644 


HISTORICAL.  645 

pose  of  supplying  the  tissues  with  oxygen  and  of  removing  the 
carbon  dioxid. 

The  true  understanding  of  the  object  of  the  act  of  respiration  we 
owe  to  Lavoisier,  the  discoverer  of  oxygen.  In  his  paper  published 
in  1777,  entitled  "Experiments  on  the  Respiration  of  Animals  and 
on  the  Changes  which  the  Air  Undergoes  in  Passing  through  the 
Lungs,"  he  laid  the  foundations  of  our  present  knowledge,  and 
in  subsequent  work  he  developed  a  conception  of  the  nature  of 
physiological  oxidations  which  has  dominated  the  physiological 
theories  of  nutrition  up  to  the  present  time.  The  discovery  of  the 
physiological  meaning  of  respiration  and  the  function  of  the  lungs 
constitutes  the  most  interesting  part  of  the  history  of  physiology. 
All  the  great  physiologists  of  past  ages  contributed  their  part  to 
the  story,  and  as  we  look  back  we  can  count  distinctly  the  different 
steps  made  toward  the  truth  as  we  understand  it  to-day.  The 
history  of  this  subject  is  not  only  most  instructive  in  demonstrating 
the  triumphant  although  slow  progress  of  scientific  investigation, 
but  it  illustrates  well  also  the  intimate  interrelations  of  physiology 
with  the  sister  sciences  of  chemistry  and  physics  and  the  great  value 
of  the  experimental  method.  The  theory  of  respiration  held  in  each 
century  was  formulated  to  explain,  as  far  as  possible,  the  facts  that 
were  known,  and  as  we  look  back  from  our  vantage  point  it  is  most 
impressive  to  realize  how  well-known  phenomena,  imperfectly 
understood,  were  apparently  explained  by  theories  which  we  now 
know  to  be  incorrect.  Without  doubt,  many  of  the  explanations 
accepted  to-day  will  in  later  times  be  found  to  rest  upon  a  similar 
incomplete  knowledge.  Each  generation  must  do  the  best  it  can 
with  the  knowledge  of  its  times. 

The  history  of  respiration,  the  successive  steps  in  its  progress  may 
be  summarized  in  a  few  words.  Aristotle  thought  that  the  main 
function  of  respiration  is  to  regulate  the  heat  of  the  body,  which  was 
supposed  to  be  produced  in  the  heart;  hence  the  increased  respira- 
tions after  muscular  exercise  when  the  body-heat  is  increased.  At 
the  same  time  he  believed,  with  the  philosophers  of  his  times,  that 
the  body  receives  something  from  the  air  that  is  necessary  to  life,  a 
subtle  something  that  he  designated  as  the  "  pneuma."  Praxagoras 
taught  that  blood  is  contained  only  in  the  veins,  and  that  the  ar- 
teries are  filled  with  a  gaseous  substance,  the  "pneuma"  derived 
from  the  air,  an  unfortunate  error  that  prevailed  in  medicine  for 
several  centuries.  The  two  celebrated  anatomists  and  physiologists 
of  the  Alexandrian  school,  Herophilus  and  Erasistratus,  distin- 
guished two  kinds  of  pneuma,  the  vital  spirits,  which  are  made  or 
extracted  from  the  air  in  the  lungs  and  whose  production  consti- 
tutes the  chief  function  of  respiration,  and  the  animal  spirits,  elabo- 
rated in  the  brain  from  the  vital  spirits  and  responsible  for  the 
functions  of  motion  and  sensation.  Galen  (131  A.  D.)  demonstrated 


646  PHYSIOLOGY    OF    RESPIRATION. 

that  the  arteries  as  well  as  the  veins  contain  blood,  but  still  believed 
that  the  chief  function  of  the  respiratory  movements  is  to  furnish 
pneuma  or  vital  spirits  to  the  heart.  This  great  physiologist  noticed 
also  that  the  air  is  necessary  for  combustion  as  it  is  for  life,  and 
stated  his  belief  that  the  explanation  of  one  of  these  acts  would 
be  also  an  explanation  of  the  other.  This  thought  seems  to  have 
been  accepted  by  all  the  physiologists  of  subsequent  times,  but  it 
required  over  sixteen  hundred  years  of  investigation  before  a  satis- 
factory solution  was  reached.  Galen  recognized,  moreover,  that 
not  only  does  the  blood  take  something  of  essential  importance  from 
the  air, — namely,  vital  spirits, — but  it  also  gives  off  something  to  the 
air  that  is  injurious  to  the  body,  a  something  which  he  compared  to 
the  smoke  of  combustion  and  designated  as  the  "  fuliginous  vapor. " 
If  we  substitute  oxygen  for  vital  spirits  and  carbon  dioxid  for 
fuliginous  vapor  we  realize  that  the  essential  problem  of  respiration 
was  already  clearly  formulated,  but  could  not  make  further  advance 
until  chemical  knowledge  was  more  fully  developed.  Such  is  the 
case  with  some  of  our  physiological  problems  to-day.  Galen  also 
explained  satisfactorily  the  respiratory  movements,  the  action  of  the 
muscles  of  inspiration  and  expiration,  thus  destroying  the  older 
erroneous  theories  that  the  expansion  and  contraction  of  the  lungs 
are  due  to  processes  of  heating  and  cooling. 

Galen's  physiology  held  undisputed  sway  until  the  seventeenth 
century.  At  that  time  there  arose  a  school  of  physiologists,  the 
iatromechanists,  who  proposed  to  explain  all  vital  phenomena  upon 
known  mechanical  principles, — the  laws  of  physics  and  chemistry. 
For  the  mystical  view  of  vital  spirits  they  proposed  to  substitute  a 
more  rational  and  concrete  theory.  The  blood  in  the  lungs  becomes 
red  simply  because  it  is  minutely  subdivided  and  shaken,  just  as  a 
tube  of  blood  becomes  red  when  violently  agitated.  Thus  an  effort 
to  be  more  scientific,  to  use  the  exact  knowledge  of  physics,  led  to 
the  adoption  of  views  which  we  now  know  were  far  more  erroneous 
than  the  ancient  and  intrinsically  correct  conception  that  the  blood 
receives  something  from  the  air  in  the  lungs. 

In  the  seventeenth  century,  however,  began  those  discoveries 
in  chemistry  and  physiology  which  eventually  led  to  our  present 
knowledge.  Van  Helmont  (1577-1644)  discovered  that  in  the 
burning  of  charcoal,  the  fermentation  of  wine,  and  the  action  of 
vinegar  on  chalk  a  special  gas  is  produced  which  he  called  gas 
sylvestre  and  which  we  call  carbon  dioxid.  Robert  Boyle  (1627- 
1691)  published  a  most  interesting  series  of  experiments  made  with 
the  aid  of  the  recently  discovered  air-pump  which  demonstrated  the 
correctness  of  the  view  held  by  Galen  that  the  air  contains  some- 
thing necessary  for  life  and  for  combustion.  He  showed,  moreover, 
that  air  that  had  been  repeatedly  inspired  was  no  longer  capable 
of  maintaining  life.  Robert  Hooke  (1635-1703)  introduced  a 


HISTORICAL.  647 

method  of  artificial  respiration  by  means  of  a  bellows,  and  demon- 
strated by  sending  a  continuous  stream  of  air  through  the  lungs 
that  the  respiratory  movements  of  these  organs  are  in  themselves, 
as  a  mechanical  process,  in  no  wise  an  essential  feature  of  respiration. 
John  Mayow  in  1688-1674  discovered  that  air  is  not  a  simple  ele- 
ment, but  contains  a  definite  substance  necessary  to  life  and  to 
combustion.  He  designated  this,  substance  as  the  nitro-aerian 
vapor  or  nitrous  particles,  because  he  believed  that  the  same 
substance  is  present  in  condensed  form,  as  it  were,  in  common  niter, 
having  found  that  combustion  is  possible  even  in  a  vacuum  in  the 
presence  of  niter. 

In  the  eighteenth  century,  as  is  shown  in  the  work  of  the  great 
physiologist,  Haller,  the  theories  of  respiration  were  in  many 
respects  in  a  most  unsatisfactory  state.  The  new  facts  that  had 
been  discovered  made  the  old  views  untenable,  but  were  not  in 
themselves  sufficient  to  explain  clearly  what  actually  takes  place. 
Such  periods  of  uncertainty  and  dissatisfaction  are  frequent  enough 
in  the  history  of  science.  In  1757  Joseph  Black  rediscovered  carbon 
dioxid,  calling  it  fixed  air,  and  showed  that  it  is  present  in  expired 
air.  A  little  later  Priestly  discovered  and  isolated  oxygen  and 
nitrogen;  but,  under  the  influence  of  an  erroneous  view  of  combus- 
tion that  had  been  advanced  by  Stahl,  was  unable  to  give  his 
discoveries  a  clear  and  satisfactory  application.  The  final  step 
in  this  progress  was  made  by  the  wonderful  work  of  Lavoisier 
between  the  years  1771  and  1780.  He  made  correct  analyses  of 
air  and  of  carbon  dioxid,  he  explained  combustion  as  an  oxidation 
with  the  formation  of  CO2  and  H2O,  he  showed  that  in  respiration 
the  same  process  occurs,  and  that  the  blood  takes  oxygen  from 
the  air  and  gives  back  to  it  in  expiration  the  carbon  dioxid  and 
water  formed  by  combustion  within  the  body.  He  gave  us  the 
essential  facts  in  the  modern  theories  of  respiration  and  physio- 
logical oxidations. 

After  Lavoisier  the  chief  positive  advances  that  have  been  made 
have  been  in  reference  to  the  condition  of  the  gases  in  the  blood. 
By  means  of  the  gas-pump  Magnus  (1837)  obtained  these  gases 
quantitatively  and  thus  procured  data  which,  as  Liebig  showed, 
demonstrate  that  the  oxygen  is  held  in  the  blood,  not  in  simple 
solution,  but  in  some  form  of  chemical  combination,  probably 
with  the  red  corpuscles.  Finally  it  was  shown  by  Stokes  and 
Hoppe-Seyler  that  the  oxygen  is  held  in  definite  chemical  com- 
bination with  the  hemoglobin.  The  nature  of  the  combination  of 
the  carbon,  dioxid  in  the  blood  is  not  yet  entirely  understood,  while 
the  actual  nature  of  physiological  oxidations — that  is,  the  part 
taken  by  the  oxygen  in  the  chemical  reactions  of  living  matter- 
is  one  of  the  great  problems  of  nutrition  which  may  need  many  years 
for  solution. 


CHAPTER  XXXIV. 

THE  ORGANS  OF  EXTERNAL  RESPIRATION  AND  THE 
RESPIRATORY  MOVEMENTS. 

Anatomical  Considerations. — Some  of  the  anatomical  ar- 
rangements in  the  lungs  which  have  an  immediate  physiological 
interest  may  be  recalled  briefly.  The  structures  of  the  trachea  and 
bronchi  are  admirably  adapted  to  their  functions  as  air  tubes,  in  that 
the  walls  possess  flexibility  combined  with  rigidity.  The  lining  of 
ciliated  epithelium  throughout  the  air  passages  is  of  importance, 
primarily  it  may  be  assumed,  in  removing  mucus  and  foreign 
material  from  these  passages.  The  smaller  bronchi  possess  a  dis- 
tinct muscular  layer,  and,  as  we  shall  see,  this  musculature  is  under 
the  control  of  a  special  set  of  nerve  fibers  through  whose  reflex 
activity  the  capacity  and  resistance  of  the  bronchial  system  may  be 
modified.  The  smallest  bronchioles  are  expanded  into  a  system  of 
membranous  air  cells,  and  in  the  walls  of  these  thin  sacs  the  capil- 
laries of  the  pulmonary  artery  are  distributed.  The  great  efficiency 
of  this  apparatus  is  evident  when  one  recalls  that  every  one  of  the 
infinite  number  of  red  corpuscles  is  exposed  separately  to  the  air  of 
the  air  cells,  so  that  although  the  time  of  transit  is  brief  the  entire 
amount  of  hemoglobin  is  nearly  completely  saturated  with  oxygen. 
Each  lung  is  enveloped  in  its  own  pleural  sac.  The  space  between 
the  parietal  and  the  visceral  layer  of  each  sac  is  the  so-called 
pleural  cavity,  but  it  must  be  borne  in  mind  that  under  all  normal 
conditions  this  cavity  is  only  potential, — that  is,  the  parietal  and 
visceral  layers  are  everywhere  in  contact  with  each  other.  Under 
pathological  or  accidental  conditions  air  or  exudations  may  enter 
this  space  and  form  an  actual  cavity.  Along  the  mid-line  of  the 
body  and  around  the  roots  of  the  lungs  we  have  the  mediastinal 
spaces  lying  between  the  pleural  sacs  of  the  two  sides,  but  entirely 
filled  with  the  various  thoracic  viscera,  such  as  the  heart,  aorta  and 
its  branches,  pulmonary  artery  and  veins,  venae  cava3,  azygos  vein, 
trachea,  esophagus,  thoracic  duct,  various  nerves,  and  lymph 
glands.  All  these  organs,  therefore,  lie  outside  the  lungs.  A 
schematic  view  of  these  relations  is  represented  in  Fig.  263. 

The  Thorax  as  a  Closed  Cavity. — The  thorax  is  a  cavity  entirely 
shut  off  from  the  outside  and  from  the  abdominal  cavity.  In  this 
cavity  lie  the  lungs  and  the  various  viscera  enumerated  above. 
The  lungs  may  be  considered  as  two  large,  membranous  sacs,  as 

648 


EXTERNAL  RESPIRATION  AND  RESPIRATORY  MOVEMENTS.     649 


represented  in  Fig.  263,  the  interior  of  which  communicates  freely 
with  the  outside  air  through  the  trachea,  glottis,  etc.,  while  the 
outside  of  the  sacs  is  protected  from  atmospheric  pressure  by  the 
walls  of  the  chest.  It  is  to  be  remembered,  of  course,  that  the 
interior  surface  of  the  lungs  is  multiplied  greatly  by  the  sub-? 
division  into  alveoli.  It  is 
estimated  that  the  entire 
inner  surface  of  the  lungs 
amounts  to  as  much  as  90 
square  meters,  over  one  hun- 
dred times  the  skin  surface 
of  the  body.  The  atmos- 
pheric pressure  on  the  interior 
surfaces  of  the  lungs  expands 
these  structures  under  normal 
conditions  until  they  fill  the 
entire  thoracic  cavity  not 
occupied  by  other  organs. 
However  the  size  of  the  chest 
cavity  varies,  that  of  the 
lungs  must  change  accord- 
ingly; so  that  at  all  times  the 
lungs  fully  fill  up  every  part 
of  the  cavity  not  otherwise 
occupied.  If  the  wall  of  the 
thorax  is  opened  at  any 
point  so  as  to  make  commu- 
nication with  the  outside  air,  or,  if  the  wall  of  the  lung  is  pierced 
so  that  the  air  can  communicate  with  the  pleural  cavity  from 
the  inside,  then  at  once  the  lungs  shrink  in  size,  since  the  atmos- 
pheric pressure  is  then  equalized  on  the  outside  and  the  inside 
of  the  sacs.  We  may  consider,  therefore,  that  the  thoracic  cavity 
is  much  larger  than  the  lungs,  and  that  the  latter  are  blown 
out  to  fill  this  cavity  by  the  atmospheric  pressure  on  the  inside. 
The  Normal  Position  of  the  Thorax — Inspiration  and  Expira- 
tion.— During  life  the  size  of  the  thorax  is  continually  changing  with 
the  respiratory  movements.  But  the  size  and  position  taken  at  the 
end  of  a  normal  expiration  may  be  regarded  as  the  normal  position 
of  the  thorax;  that  is,  its  position  when  all  of  the  muscles  of  respira- 
tion are  at  rest,  and  substantially,  therefore,  the  position  of  the 
thorax  in  the  cadaver.  Starting  from  this  position,  any  enlarge- 
ment of  the  thorax  constitutes  an  active  inspiration,  the  result  of 
which  will  be  to  draw  more  air  into  the  lungs  ;  while  starting  from 
the  normal  position  any  diminution  in  the  size  of  the  thorax 
constitutes  an  active  expiration,  which  will  drive  some  air  out  of  the 
lungs.  It  is  evident,  however,  that  after  an  active  inspiration  the 


Fig.  263. — Schema  to  indicate  the  re- 
lations of  the  parietal  and  visceral  layers  of 
the  pleural  sacs,  and  the  position  of  the  me- 
diastinal  space:  P,  the  potential  pleural 
cavity  in  each  sac;  M,  the  mediastinal 
space:  R.L.  and  L.L.,  the  cavity  of  the 
right  and  the  left  lung,  respectively ;  T,  the 
trachea.  The  outlines  of  the  pleura  on  each 
side  are  represented  in  dotted  lines. 


650  PHYSIOLOGY  OF   RESPIRATION. 

thorax  may  return  passively  to  its  normal  position,  giving  what  is 
known  as  a  passive  expiration, — that  is,  an  expiration  not  caused 
by  muscular  effort.  So  after  an  active  expiration  the  thorax  may 
return  passively  to  its  normal  position,  giving  a  passive  inspiration. 
Our  normal  respiratory  movements  consist  of  an  active  inspiration 
followed  by  a  passive  expiration, 

Mechanism  of  the  Inspiration. — The  chest  cavity  may  be 
enlarged  and  an  inspiration,  therefore,  be  produced  by  two  methods, 
— namely,  by  a  contraction  of  the  diaphragm  and  by  an  elevation 
of  the  ribs. 

Contraction  of  the  Diaphragm. — From  the  anatomy  of  the 
diaphragm  it  is  evident  that  its  fixed  attachment  is  found  in  its 
muscular  connections  with  the  lumbar  vertebrae,  the  ribs,  and  the 
ensiform  cartilage.  From  these  attachments  the  muscular  sheet 
extends  anteriorly  along  the  walls  of  the  thorax  and  then  bends  over 
to  form  the  arch  which  ends  in  the  central  tendon.  This  latter 
structure  is  not  entirely  free,  since  it  is  attached  to  the  pericar- 
dium of  the  heart ;  but,  relatively,  it  is  the  movable  portion  of 
the  diaphragm.  Speaking  generally,  a  contraction  of  the  dia- 
phragmatic muscle  draws  the  central  tendon  downward  toward  the 
abdominal  cavity  and  therefore  enlarges  the  chest  in  the  vertical 
diameter,  while  an  increase  in  the  thoracic  cavity  around  the 
periphery  of  the  diaphragm  is  caused  also  by  the  flattening  of  the 
muscular  arch.  Two  results  follow  this  movement:  The  lungs  are 
expanded  exactly  in  proportion  as  the  cavity  enlarges.  There  is, 
of  course,  at  no  time  any  space  between  the  lungs  and  the  dia- 
phragm: as  the  latter  moves  downward  the  lungs  follow  because  of 
the  excess  of  pressure  on  their  interior.  Although  ordinarily  we 
speak  of  the  new  air  being  sucked  into  the  lungs  during  this  move- 
ment, it  is,  of  course,  strictly  speaking,  forced  in  by  the  pressure  of 
the  outside  atmosphere.  On  the  other  hand,  the  descent  of  the  dia- 
phragm raises  the  pressure  in  the  abdominal  cavity.  This  cavity  is 
entirely  full  of  viscera  and  for  mechanical  purposes  may  be  regarded 
as  being  full  of  liquid.  The  rise  of  pressure  is  transmitted  throughout 
the  abdomen  and  causes  the  abdominal  wall  to  protrude.  Inspiration 
caused  by  a  contraction  of  the  diaphragm  is  therefore  spoken  of 
either  as  diaphragmatic  respiration  or 'as  abdominal  respiration,  the 
latter  term  having  reference  to  the  visible  effect  on  the  abdominal 
walls.  In  strong  contractions  of  the  diaphragm  the  heart  also  is 
pulled  downward,  and  if  the  movement  is  forced  the  lower  ribs  may 
be  pulled  inward  to  some  extent.  This  last  effect  would  diminish 
the  size  of  the  thorax  and  therefore  would  tend  to  antagonize  the 
inspiratory  action  of  the  diaphragm,  and  other  muscles  are  appar- 
ently brought  into  play  to  prevent  this  result.  As  stated  below,  the 


EXTERNAL  RESPIRATION  AND  RESPIRATORY  MOVEMENTS.     651 


Fig.  264.— Sixth   dorsal    vertebra   and 
rib.— (Reichert.) 


quadratus  lumborum  and  the  serratus  posticus  inferior  may  have 

this  function  of  fixating  the  lower 
ribs  in  violent  inspirations.  The 
diaphragmatic  muscle  is  innervated 
on  each  side  by  the  corresponding 
phrenic  nerve.  This  nerve  arises 
in  the  neck  from  the  fourth  and 
fifth  cervical  spinal  nerves,  and 
passes  downward  in  the  chest  in 
the  mediastinal  space,  lying  close 
to  the  heart  in  part  of  its  course. 
Section  of  this  nerve  paralyzes,  of 
course,  the  diaphragm  on  the  cor- 
responding side. 

Elevation  of  the  Ribs. — As  a 
necessary  result  of  the  structure  of 
the  bony  thorax,  every  elevation 
of  the  ribs  must  cause  an  enlarge- 
ment of  the  thoracic  cavity  in  the 
dorsoventral  and  the  lateral  diam- 
eters. We  are  justified  in  saying 
that  every  muscle  whose  contrac- 
tion causes  an  elevation  of  the  ribs  is  an  inspiratory  muscle.  This 
result  is  due,  in  the  first  place,  to  the  slant 
of  the  ribs.  Each  rib  is  attached  to  the 
spinal  column  at  two  points :  the  head  to 
the  body  of  the  vertebra  and  the  tubercle 
to  the  transverse  process.  The  up-and- 
down  movements  of  the  ribs  may  be  re- 
garded as  rotations  around  an  axis  joining 
these  two  points, — that  is,  each  point  in 
the  rib  as  it  moves  up  or  down  describes 
a  circle  around  this  axis  (see  Fig.  264). 
If  our  ribs  were  set  upon  the  vertebral  col- 
umn so  that  the  plane  of  the  rib  formed  a 
right  angle  with  the  column,  then  every 
movement  of  the  rib  up  or  down  would 
decrease  the  size  of  the  thorax  and  there- 
fore cause  an  expiration.  As  a  matter 
of  fact,  however,  the  ribs  slant  downward, 
so  that  if  elevated  the  sternal  end  is  car- 
ried farther  away  from  the  sternum  and 
the  chest  is  enlarged  in  the  dorsoventral 
direction  (see  Fig.  265) .  Moreover,  as  the  rib  moves  upward  there 


Fig.  265.— Diagram  to  il- 
lustrate the  effect  of  the  slant 
of  the  ribs:  AS,  The  spinal  col- 
umn; a,  the  position  of  the 
rib  in  normal  expiration ;  (aO 
its  position  (exaggerated)  in 
inspiration  (the  distance  be- 
tween the  spinal  column  and 
the  sternum  («£.),  the  antero- 
posterior  or  dorsoventral  di- 
ameter of  the  chest  is  in- 
creased). Any  movement  from 
the  position  a'  would  cause  an 
expiration. 


652  PHYSIOLOGY  OF  RESPIRATION. 

is  an  obvious  enlargement  of  the  chest  in  the  lateral  diameter. 
This  result  may  be  referred  to  two  causes :  In  the  first  place,  the 
axis  of  the  rotation  of  the  ribs, — that  is,  the  line  joining  the  head 
and  the  tubercle  of  the  rib  is  inclined  downward  so  that  the  plane 
of  rotation,  which  is,  of  course,  at  right  angles  to  this  axis,  will  be 
inclined  outward.  As  the  rib  is  moved  upward,  therefore,  it  must 
also  move  outward.  Secondly  the  cartilaginous  ends  of  the  ribs  are 
fixed  at  the  sternum  so  that  as  they  move  upward  and  outward 
they  will  be  twisted  or  everted  somewhat  in  the  middle,  with  a 
torsion  of  the  cartilaginous  ends. 

The  Muscles  of  Inspiration. — In  addition  to  the  diaphragm, 
all  muscles  attached  to  the  thorax  whose  contraction  causes  an 
elevation  of  the  ribs  must  be  classed  as  inspiratory  muscles.  In 
regard  to  this  latter  group  the  action  of  some  of  them  is  either 
evident  from  their  anatomical  attachments,  or  the  muscles  may  be 
stimulated  directly  and  the  effect  of  their  contraction  be  noted.  In 
other  cases,  however,  it  is  necessary  to  make  use  of  the  method 
first  suggested  by  Newell  Martin, — namely,  the  determination 
•whether  the  contraction  of  the  muscle  in  respiration  occurs  simul- 
taneously with  that  of  the  diaphragm  or  alternately  with  it.  In  the 
former  case  it  is  inspiratory,  in  the  latter  expiratory.  The  following; 
muscles  may  be  classed  as  inspiratory:  Levatores  costarum.  They 
arise  from  transverse  processes  of  the  seventh  cervical  and  first  to 
eleventh  thoracic  vertebrae  and  are  inserted  into  the  next  rib  or  the 
second  rib  below.  Intercostales  externi  muscles.  They  lie  in  the  inter- 
costal spaces  extending  from  the  lower  edge  of  one  rib  to  the  upper 
edge  of  the  rib  below;  they  slant  downward  and  toward  the  mid-line. 
These  muscles  have  been  assigned  different  functions  by  different 
authors,  but  the  experiments  made  by  Hough,*  using  the  method 
of  Martin  described  above,  show  that  they  are  inspiratory.  It 
was  found  that  in  the  dog  they  contract  synchronously  with  the 
diaphragm.  The  same  authors  find  that  the  intercartilaginous 
portions  of  the  internal  intercostals  are  also  inspiratory.  The 
scaleni — anterior,  medius,  and  posterior — arise  from  the  transverse 
processes  of  the  cervical  vertebrae  and  are  inserted  into  the  first  and 
second  ribs.  M.  sterno-cleido-mastoideus  extends  from  the  mastoid 
process  to  the  sternum  and  sternal  extremity  of  the  clavicle.  M. 
pectoralis  minor  extends  from  the  coracoid  process  of  the  scapula 
to  the  anterior  surface  of  the  second  to  the  fifth  rib.  M.  serratits 
posticus  superior  extends  from  the  spinous  processes  of  the  lower 
cervical  and  upper  dorsal  vertebrae  to  the  second  to  fifth  rib. 

The  Muscles  of  Expiration. — Expiration — that  is,  diminution 

*  Hough,  "  Studies  from  the  Biological  Laboratory,  John  Hopkins 
University,"  5,  91,  1893,  and  Bergendal  and  Bergman,  "  Skandinavisches 
Archiv  f.  Physiologie, "  7,  178,  1896. 


EXTERNAL  RESPIRATION  AND  RESPIRATORY  MOVEMENTS.      653 

in  size  of  the  thorax — may  also  be  produced  in  two  ways:  First, 
by  forcing  the  diaphragm  farther  into  the  thoracic  cavity.  This 
result  is  obtained,  not  by  any  direct  action  of  the  diaphragm,  but 
by  contracting  the  muscular  walls  of  the  abdomen,  the  external  and 
internal  oblique,  the  rectus,  and  the  transversus.  The  contraction 
of  these  muscles,  which  form  what  has  been  called  the  abdominal 
press,  raises  the  pressure  in  the  abdomen  and  this,  acting  upon  the 
under  surface  of  the  diaphragm,  forces  it  up  into  the  thorax,  pro- 
vided the  glottis  is  open.  If  the  glottis  is  kept  closed  firmly  the 
increased  abdominal  pressure  is  felt  mainly  upon  the  pelvic  organs, 
and  this  effect  is  observed  in  micturition,  defecation,  and  parturition. 
Second,  by  depressing  the  ribs.  The  muscles  which  may  be  sup- 
posed to  exert  this  action  are  as  follows:  M.  intercostales  intemi. 
The  expiratory  action  of  these  muscles,  so  far  as  the  interosseous 
portion  is  concerned,  was  first  definitely  shown  by  Martin,  who 
proved  that  when  they  contract  they  act  alternately  with  the  dia- 
phragm. *  M .  triangularis  sterni  or  the  ra .  transversus  thoracis  is  found 
on  the  interior  of  the  thorax  on  the  anterior  wall.  Its  fibers  pass 
from  the  sternum,  running  upward  and  outward,  to  be  inserted  into 
the  third  to  sixth  rib.  The  expiratory  action  of  this  muscle  was 
demonstrated  by  Hough  according  to  the  method  of  Martin.  M. 
Hiocostalis  lumborum.  The  anatomical  attachments  of  this  muscle 
are  such  as  would  enable  it  to  depress  the  ribs;  but  its  functional 
activity  in  expiration  has  not  been  demonstrated.  The  m.  serratus 
posticus  inferior  and  m.  quadratus  lumborum  are  both  placed 
anatomically,  especially  the  former,  so  that  their  contractions 
serve  to  depress  the  ribs.  It  has  been  suggested,  however,  that 
they  may  act  in  forced  inspirations  so  as  to  antagonize  the  ten- 
dency of  the  diaphragm  to  pull  the  lower  ribs  inward.  Whether 
they  really  act  with  the  diaphragm  or  alternately  with  it  can  only  be 
determined  by  actual  experiment. 

Quiet  and  Forced  Respiratory  Movements;  Eupnea  and 
Dyspnea. — Our  respiratory  movements  vary  much  in  amplitude, 
and  the  muscles  actually  involved  differ  naturally  with  the  extent 
of  the  movement.  In  general,  we  distinguish  two  different  forms  of 
breathing  movements.  The  ordinary  quiet  respirations,  made 
without  obvious  effort,  form  a  condition  of  respiration  designated 
as  eupnea.  Difficult  or  labored  breathing  is  known  as  dyspnea. 
It  is  impossible  to  draw  a  sharp  line  between  the  two.  There  are 
many  degrees  of  dyspnea,  and  doubtless  in  quiet  breathing  the 
amplitude  of  the  movements  may  vary  considerably  before  they 
become  distinctly  dyspneic.  In  all  conditions  of  eupnea  the  chief 
point  to  bear  in  mind  is  that  the  expiration  is  entirely  passive. 
*  Martin  and  Hartwell,  "  Journal  of  Physiology, "  2,  24,  1879. 


654  PHYSIOLOGY    OF    RESPIRATION. 

The  inspiration  in  man  is  made  by  the  diaphragm  alone  or  b}-  the 
diaphragm  together  with  some  action  of  the  levatores  costarum  and 
the  external  intercostals.  At  the  end  of  the  inspiration  the  ribs  and 
diaphragm  are  brought  back  to  the  normal  position  by  purely 
physical  forces, — the  elasticity  of  the  distended  abdominal  wall, 
the  elasticity  of  the  expanded  lungs,  the  weight  and  torsion  of 
the  ribs,  etc.  As  soon  as  the  breathing  movements  become  at  all 
forced  the  action  of  the  above-named  inspiratory  muscles  is  in- 
creased in  intensity,  and  the  other  inspiratory  muscles,  all  elevators 
of  the  ribs,  come  into  play.  Quiet  breathing  in  man  at  least  is 
mainly  diaphragmatic  or  abdominal,  while  dyspneic  breathing  is 
characterized  by  a  greater  action  of  the  elevators  of  the  ribs. 
When  dyspnea  reaches  a  certain  stage  the  expiration  also  becomes 
active  or  forced.  The  expiratory  act  is  hastened  by  a  contraction 
of  the  abdominal  muscles  or  of  the  depressors  of  the  ribs,  and 
indeed  the  action  of  these  muscles  may  compress  the  chest  beyond 
its  normal  position,  so  that  the  expiration  is  followed  by  a  passive 
inspiration  which  brings  the  chest  to  its  normal  position  before  the 
next  active  inspiration  begins. 

Costal  and  Abdominal  Types  of  Respiration. — These  two 
types  of  respiration  are  based  upon  the  character  of  the  inspiratory 
movement.  An  inspiration  in  which  the  movement  of  the  abdomen, 
due  to  contraction  of  the  diaphragm,  is  the  chief  or  only  feature 
belongs  to  the  abdominal  type.  An  inspiration  in  which  the  eleva- 
tion of  the  ribs  is  a  noticeable  factor  belongs  to  the  costal  type. 
Hutchinson,  who  introduced  this  nomenclature,*  laid  emphasis 
chiefly  upon  the  order  of  the  movements.  In  the  abdominal 
type  the  abdomen  bulges  outward  first,  and  this  is  followed  by 
a  movement  of  the  thorax;  the  movement  spreads  from  the 
abdomen  to  the  thorax,  and,  "  like  a  wave,  is  lost  over  the  thoracic 
region."  In  costal  breathing  the  upper  ribs  move  first  and  the 
abdomen  second.  The  terms  are  meant  to  apply  chiefly  to  human 
respiration  and  have  aroused  interest  in  connection  with  the 
fact  that  in  quiet  breathing  in  the  erect  posture  the  respiration 
of  man  belongs  to  the  abdominal  type  and  that  of  woman  to  the 
costal  type.  It  has  been  a  question  whether  this  difference  is  a 
genuine  sexual  distinction  or  depends  simply  upon  differences 
in  dress.  Hutchinson  inclined  to  the  view  that  it  forms  what  we 
should  call  a  secondary  sexual  characteristic,  and  that  its  physio- 
logical value  for  woman  lies  in  the  fact  that  provision  is  thus  made, 
as  it  were,  against  the  period  of  pregnancy.  He  states  that  in 
twenty-four  young  girls  examined  between  the  ages  of  eleven  and 
fourteen  the  costal  type  was  present,  although  none  of  them  had 

*  See  Hutchinson,  article  on  "Thorax,"  Todd 's  " Cyclopaedia  of  Anat- 
omy and  Physiology, "  1849. 


EXTERNAL  RESPIRATION  AND  RESPIRATORY  MOVEMENTS.      655 

worn  tight  dress.  Later  observers,  however  (Mays,  Kellogg,  and 
others),  state  that  Indian  and  Chinese  women  who  have  not  worn 
tight  dress  exhibit  the  abdominal  type,  and  the  same  statement  is 
made  regarding  civilized  white  women  who  habitually  wear  loose 
clothing.  It  would  appear,  therefore,  that  the  assumption  of  the 
costal  type  by  women  in  general  is  due  to  the  hindrance  offered  by 
the  clothing  to  the  movements  of  the  abdomen.  From  an  exami- 
nation of  four  hundred  and  seven  cases  Fitz  *  concludes  that  when 
the  restricting  effect  of  dress  is  removed  there  is  little  or  no  differ- 
ence in  the  type  of  respiration  in  the  two  sexes.  The  natural  type 
is  one  in  which  "  the  movement  is  fairly  equally  balanced  between 
chest  and  abdomen,  the  abdominal  being  somewhat  in  excess." 
When  the  respiration  becomes  dyspneic  it  takes  on  a  distinctly 
costal  type,  and  Fitz  and  others  have  shown  that  for  an  equal  in- 
crease in  girth  the  thoracic  movements  cause  a  greater  enlargement 
of  the  lungs. 

Accessory  Respiratory  Movements. — In  addition  to  the  mus- 
cles whose  action  directly  enlarges  or  diminishes  the  capacity  of  the 
thorax  certain  other  muscles  connected  with  the  air  passages  con- 
tract rhythmically  with  the  inspirations,  and  may  be  designated 
properly  as  accessory  muscles  of  inspiration.  The  muscles  es- 
pecially concerned  are  those  controlling  the  size  of  the  glottis  and 
the  opening  of  the  external  nares.  At  each  inspiration  the  elevators 
of  the  wings  of  the  nose  come  into  play.  This  movement  occurs  in 
normal  breathing  in  many  animals,  such  as  the  rabbit  and  horse, 
and  in  some  men,  while  in  dyspneic  breathing  it  is  invariably 
present.  The  useful  result  of  the  movement  is  to  reduce  the  resis- 
tance to  the  inflow  of  air.  So  in  many  animals  the  glottis  is  dilated 
at  each  inspiration  by  the  contraction  of  the  posterior  crico-aryte- 
noid  muscles,  and  in  man  also  this  movement  is  evident  when 
the  breathing  is  at  all  forced.  The  useful  result  in  this  case  also  is 
a  reduction  in  the  resistance  offered  to  the  inflow  of  air. 

The  Registration  of  the  Rate  and  Amplitude  of  the  Respira- 
tory Movements. — Many  methods  are  employed  to  register  the 
rate  or  amplitude  of  the  respiratory  movements.  Upon  man  the 
amplitude  may  be  measured  directly  by  a  tape  placed  at  different 
levels  to  ascertain  the  increase  in  girth,  or  it  may  be  recorded  by 
some  form  of  lever  or  tambour  applied  to  the  chest  or  abdomen. 
A  convenient  instrument  for  this  purpose  is  the  pneumograph 
described  by  Marey,  which  is  illustrated  and  described  in  Fig.  266. 
In  animal  experimentation  the  various  methods  that  are  employed 
may  be  classified  under  four  heads:  (1)  Methods  in  which  the 
change  in  circumference  or  diameter  of  the  chest  or  abdomen  is 
recorded.  (2)  Methods  in  which  the  change  of  pressure  in  the  air 
*  Fitz,  "Journal  of  Experimental  Medicine/'  1,  1896. 


656  PHYSIOLOGY    OF    RESPIRATION. 

passages  is  recorded.  In  these  methods  a  tube  may  be  inserted  into 
one  of  the  nostrils  for  instance,  and  then  connected  to  a  tambour  the 
lever  of  which  makes  its  record  on  a  kymographion,  or  if  the  animal 
is  tracheotomized  a  side  tube  upon  the  tracheal  cannula  may  be 
connected  to  a  tambour.  This  method  indicates  well  the  rate  of 
movement  and  the  relative  amplitude,  but  has  the  defect  that  it 


Fig.  266. — Figure  of  Marey's  pneumograph. — (Verdin.)  The  instrument  consists  of 
a  tambour  (.£),  mounted  on  a  flexible  metal  plate  (p).  By  means  of  the  bands  c  and  c 
the  metal  plate  is  tied  to  the  chest.  Any  increase  or  decrease  in  the  size  of  the  chest  will 
then  affect  the  tambour  by  the  lever  arrangement  shown  in  the  figure.  These  changes  in 
the  tambour  are  transmitted  through  the  tube  r  as  pressure  changes  in  the  contained  air 
to  a  second  tambour  (not  shown  in  the  figure)  which  records  them  upon  a  smoked  drum. 

does  not  record  the  pause,  if  any,  at  the  end  of  inspiration  or  ex- 
piration. A  modification  of  this  method  that  permits  an  accurate 
record  of  the  amplitude  and  duration  of  the  movements  consists  in 
connecting  the  trachea  or  nostrils  with  a  large  bottle  of  air.  The 
animal  breathes  into  and  out  of  the  bottle,  and  the  corresponding 


Fig.  267. — Curve  of  normal  respiratory  movements. — (Marey.)  Curve  A ,  full  line, 
represents  the  movements  when  the  respiration  is  entirely  normal.  Downstroke,  inspira- 
tion;  upstroke,  expiration.  CurveO,  dotted  line,  represents  the  increased  amplitude  of  the 
movements,  slight  dyspnea,  caused  by  breathing  through  a  narrow  tube. 

variations  in  pressure  are  recorded  by  a  tambour  also  connected 
with  the  interior  of  the  bottle.  (3)  Methods  in  which  the  change 
of  pressure  in  the  thoracic  cavity  is  recorded.  This  end  may  be 
reached  by  inserting  a  cannula  into  the  thoracic  wall  so  that  its 
opening  lies  in  the  pleural  cavity,  or,  more  simply,  a  catheter  or 
sound  connected  at  the  other  end  to  a  tambour  may  be  passed  down 
the  esophagus  until  its  end  lies  in  the  intrathoracic  portion. 
Variations  in  pressure  in  the  mediastinal  space  synchronous  with 
the  respiratory  movements  affect  the  esophagus  and  through  it 
the  sound.  (4)  Methods  in  which  the  movements  of  the  dia- 
phragm are  recorded  either  by  a  tambour  or  lever  thrust  between 


EXTERNAL  RESPIRATION  AND  RESPIRATORY  MOVEMENTS.       657 


the  diaphragm  and  liver,  or  by  hooks  attached  directly  to  muscular 
slips  of  the  diaphragm.  Registration  of  the  movements  in  man 
during  quiet  breathing  give  us  such  a 
record  as  is  seen  in-  Fig.  267.  It  will 
be  seen  that  the  inspiration  (descend- 
ing limb)  is  followed  at  once  by  an 
expiration,  as  we  should  expect, 
since,  as  soon  as  the  inspiratory 
muscles  cease  to  act,  the  physical 
factors  mentioned  above  at  once  tend 
to  bring  the  chest  back  to  its  normal 
position.  The  expiration  (ascending 
limb)  is  at  first  rapid  and  toward  the 
end  very  gradual,  so  that  there  is  al- 
most a  condition  of  rest, — an  expira- 
tory pause. 

The  Volumes  of  Air  Respired 
and  the  Capacity  of  the  Lungs. — 
The  volume  of  air  respired  varies,  of 
course,  with  the  extent  of  the  move- 
ments and  the  size  of  the  individual. 
This  volume  may  be  determined 
readily  in  any  given  case  by  means 
of  a  spirometer, — a  form  of  gasometer 
adapted  to  this  purpose.  The  con- 
struction of  this  apparatus  is  repre- 
sented in  Fig.  268.  It  consists  of  a 
graduated  cylinder  (A)  and  a  receiver 
(B}  filled  with  water.  The  cylinder 
A  is  counterbalanced  by  a  weight  (g) 
so  as  to  move  up  and  down  in  the 
water  of  B  with  the  least  possible  re- 
sistance.  The  tube  C  passes  through 
the  wall  of  B  and  ends  in  the  interior  of  A  above  the  level  of  the 
water.  The  free  end  of  this  tube  is  connected  with  the  mouth 
or  nose.  When  one  breathes  through  this  tube  the  expired  air 
passes  into  A,  which  rises  from  the  water  to  receive  it.  If  A  is 
graduated  the  amount  of  air  breathed  out  may  be  measured 
directly.  The  following  terms  are  used:  Vital  capacity.  By 
vital  capacity  is  meant  the  quantity  of  air  that  can  be  breathed 
out  by  the  deepest  possible  expiration  after  making  the  deepest 
possible  inspiration.  It  gives  a  rough  measure  of  lung  capacity, 
and  is  used  in  gymnasiums  and  physical  examinations  for  this  pur- 
pose. The  actual  amount  varies  with  the  individual;  an  average 
figure  for  the  adult  man  is  3700  c.c.  Tidal  air.  By  this  term  is 
meant  the  amount  of  air  breathed  out  in  a  normal  quiet  expiration. 
42 


Fig.    268.— Wintrich 's     modifi- 
spirometer. 


658  PHYSIOLOGY    OF    RESPIRATION. 

A  similar  amount  is  breathed  in,  of  course,  in  the  previous  inspira- 
tion, and  the  term  tidal  air  designates  the  amount  of  air  that  flows 
in  and  out  of  the  lungs  with  each  quiet  respiratory  movement. 
Here,  again,  there  are  individual  variations.  The  average  figure 
for  the  adult  man  is  500  c.c.  The  complemental  air.  This  term 
designates  the  amount  of  air  that  can  be  breathed  in  over  and  above 
the  tidal  air  by  the  deepest  possible  inspiration.  It  is  estimated 
at  1600  c.c.  The  supplemental  air.  By  this  term  is  meant  the 
amount  of  air  that  can  be  breathed  out,  after  a  quiet  expiration,  by 
the  most  forcible  expiration.  It  is  equal  also  to  1600  c.c.  It  is 
evident  that  the  complemental  air  plus  the  supplemental  air  plus 
the  tidal  air  constitute  the  vital  capacity.  The  residual  air.  After 
the  most  forcible  expiration  the  lungs  are  far  from  being  entirely 
collapsed.  The  volume  of  air  that  remains  behind,  after  the  sup- 
plemental air  has  been  driven  out,  is  known  as  the  residual  air. 
The  amount  of  this  air  has  been  estimated  directly  on  the  cadaver 
(Hermann).  The  thorax  was  first  pressed  into  a  position  of  forced 
expiration;  the  trachea  was  then  ligated,  the  chest  opened,  the  lungs 
removed  and  their  volume  estimated  by  the  amount  of  water  dis- 
placed when  they  were  immersed.  The  average  result  from  such 
estimations  was,  in  round  numbers,  1000  c.c.  Under  conditions  of 
normal  breathing  the  reserve  supply  of  air  in  the  lungs  is  equal  to 
the  residual  air  plus  the  supplemental  air, — that  is,  2600  c.c.  Mini- 
mal air.  When  the  thorax  is  opened  the  lungs  collapse,  driving  out 
the  supplemental  and  residual  air,  but  not  quite  completely.  Before 
the  air  cells  are  entirely  emptied  the  small  bronchi  leading  to  them 
collapse  and  their  walls  adhere  with  sufficient  force  to  entrap  a  little 
air  in  the  alveoli.  It  is  on  this  account  that  the  excised  lungs  float 
in  water  and  are  designated  as  lights  by  the  butcher.  The  small 
amount  of  air  caught  in  this  way  is  designated  as  the  minimal  air. 

In  the  fetus  before  birth  the  lungs  are  entirely  solid,  but  after 
birth,  if  respirations  are  made,  the  lungs  do  not  collapse  completely 
on  account  of  the  capture  of  the  minimal  air.  Whether  or  not  the 
lungs  will  float  has  constituted,  therefore,  one  of  the  facts  used  in 
medicolegal  cases  to  determine  if  a  child  was  stillborn.  The  lungs 
during  life  may,  under  certain  conditions,  again  become  in  parts 
entirely  solid.  If  any  of  the  alveoli  become  completely  shut  off 
from  the  trachea,  by  an  accident  or  by  pathological  conditions,  the 
air  caught  in  them  may  be  completely  absorbed,  after  a  certain 
interval,  by  the  circulating  blood. 

The  Size  of  the  Bronchial  Tree  and  the  Ventilation  of  the 
Lungs. — Since  the  reserve  supply  of  air  in  the  lungs  may  amount  to 
2600  c.c.,  while  the  new  air  breathed  in  at  each  inspiration  amounts 
to  only  500  c.c.,  it  would  seem  at  first  that  the  alveolar  air  is  not 
very  efficiently  renewed  by  a  quiet  inspiration.  The  actual  amount 
of  ventilation  effected  depends  on  the  capacity  of  the  bronchial 


EXTERNAL  RESPIRATION  AND  RESPIRATORY  MOVEMENTS.        659 

tree,  sometimes  known  as  the  "dead  space"  of  the  lungs,  since 
the  air  filling  this  space  is  not  useful  in  the  respiratory  processes. 
The  average  size  of  the  "dead  space"  is  of  importance  in  many  of 
the  calculations  in  regard  to  the  extent  of  respiratory  exchange,  but 
the  figures  reported  by  different  experimenters  vary  considerably. 
According  to  observations  based  mainly  on  anatomical  measure- 
ments* the  volume  of  the  dead  space  has  been  reckoned  usually  as 
equal  to  about  140  c.c.  for  the  adult.  Some  recent  observers  mak- 
ing use  of  an  indirect  method  ;of  calculation  based  upon  the  con- 
centration of  the  CO2  in  the  expired  air  and  the  alveolar  air  have 
stated  that  the  size  of  the  dead  space  may  vary  with  conditions. 
In  the  dyspnea  or  hyperpnea  due  to  muscular  exercise  it  may 
be  increased  to  as  much  as  600+  c.c.  (Douglas  and  Haldane)  on 
account  of  a  dilatation  of  the  bronchioles  or  atria.  Others,  while 
admitting  some  variation  with  differences  in  the  extent  of  the 
respiratory  movements,  state  that  the  variation  is  relatively 
small,  lying  between  limits  of  100  to  200  c.c.f  If  we  accept  the 
figures,  140  c.c.,  as  representing  a  mean  value,  then  at  each  inspira- 
tion at  least  360  c.c.  of  air  penetrate  into  the  alveoli,  and  if  evenly 
disseminated  through  the  lungs  add  about  -f^  to  the  volume  of 
each  alveolus.  Once  in  the  alveoli,  diffusion  must  tend  to  spread 
the  tidal  air  rapidly,  and  that  this  occurs  is  shown  by  an  interesting 
experiment  performed  by  Gre"hant.  He  breathed  in  500  c.c.  of 
hydrogen  instead  of  air  and  then  examined  the  amounts  of  hy- 
drogen breathed  out  in  successive  expirations.  Only  170  c.c. 
were  recovered  in  the  first  expiration,  180  c.c.  in  the  second,  41  in 
the  third,  and  40  in  the  fourth. 

Artificial  Respiration. — In  laboratory  experiments  artificial 
respiration  is  employed  frequently  after  the  use  of  curare ;  when  it  is 
necessary  to  open  the  chest:  after  cessation  of  respirations  from 
overdoses  of  chloroform  or  ether,  etc.  The  method  used  in  almost 
all  cases  is  the  reverse  of  the  normal  procedure, — that  is,  the  lungs 
are  expanded  by  positive  pressure  (pressure  in  excess  of  atmos- 
pheric). A  bellows  or  blast  worked  by  hand  or  machinery  is  con- 
nected with  the  trachea  and  the  lungs  are  dilated  by  rhythmical 
strokes.  Provision  is  made  for  the  escape  of  expired  air  by  the  use 
of  valves  or  by  a  side  hole  in  the  tracheal  cannula.  Numerous 
forms  of  respiration  pumps  have  been  devised  for  this  purpose. 

In  cases  of  suspended  respiration  in  human  beings  from  drown- 
ing, electrical  shocks,  pressure  upon  the  medulla,  etc.,  it  is  necessary 
to  use  artificial  respiration  in  order  to  restore  normal  breathing. 
Bellows  ordinarily  cannot  be  used  in  such  cases.  Some  method 

*  See  Loewy,  "Archiv  f.  die  gesammte  Physiologie,"  58,  416. 
f  Krogh  and  Lindhard,  "Journal  of  Physiology,"  41,  59,  1917;  also  Pearce, 
"American  Journal  of  Physiology,"  43,  73,  1917. 


660  PHYSIOLOGY    OF    RESPIRATION. 

must  be  employed  to  expand  and  contract  the  chest  alternately,  and 
several  different  ways  have  been  devised.  The  Marshall  Hall 
method  consists  in  placing  the  subject  face  down  and  rolling  the 
body  from  this  to  a  lateral  position,  making  some  pressure  upon  the 
back  while  in  the  prone  position.  The  Sylvester  method,  which  is 
frequently  used,  consists  in  raising  the  arms  above  the  head  and 
then  bringing  them  down  against  the  sides  of  the  chest  so  as  to 
compress  the  latter.  The  Howard  method  consists  in  simply  com- 
pressing the  lower  part  of  the  chest  while  the  subject  is  in  a  supine 
position.  Schaefer,  who  has  recently  compared  these  different 
methods,  suggests  one  of  his  own,  which  seems  to  be  effective,  saves 
labor,  and  is  less  injurious  to  the  subject.*  He  describes  it  as  fol- 
lows: "It  consists  in  laying  the  subject  in  the  prone  posture, 
preferably  on  the  ground,  with  a  thick  folded  garment  underneath 
the  chest  and  epigastrium.  The  operator  puts  himself  athwart  or 
at  the  side  of  the  subject,  facing  his  head  (see  Fig.  269)  and  places 
his  hands  on  each  side  over  the  lower  part  of  the  back  (lowest  ribs). 
He  then  slowly  throws  the  weight  of  his  body  forward  to  bear  upon 


Fig.  269.— Shows  the  position   to    be  adopted  for  effecting  artificial  respiration  in  cases 
of  drowning. — (Schaefer.) 

his  own  arms,  and  thus  presses  upon  the  thorax  of  the  subject  and 
forces  air  out  of  the  lungs.  This  being  effected,  he  gradually  re- 
laxes the  pressure  by  bringing  his  own  body  up  again  to  a  more 
erect  position,  but  without  moving  the  hands."  These  movements 
are  repeated  quite  regularly  at  a  rate  of  twelve  to  fifteen  times  a 
minute  until  normal  respiration  begins  or  the  possibility  of  its 
restoration  is  abandoned.  A  half-hour  or  more  may  be  required 
before  normal  breathing  movements  start. 

*Schafer,    "Medico-chirurgical    Transactions,"    London,    vol.    Ixxxvii., 
1904;  also  "Journal  of  the  American  Medical  Association,"  51,  801,  1908. 


CHAPTER  XXXV. 


THE  PRESSURE   CONDITIONS   IN  THE  LUNGS  AND 

THORAX  AND  THEIR  INFLUENCE  UPON  THE 

CIRCULATION. 

In  considering  the  pressure  changes  in  respiration  the  distinction 
between  the  pressure  in  the  thorax  outside  the  lungs  and  the  pres- 
sure within  the  lungs  and  air  passages  must  be  kept  clearly  in  mind. 
The  pressure  in  the  thoracic  cavity  outside  the  lungs  may  be 
designated  as  the  intrathoracic  pressure;  it  is  the  pressure  exerted 
upon  the  heart,  great  blood- 
vessels, thoracic  duct,  esopha- 
gus, etc.  The  pressure  in  the 
interior  of  the  lungs  and  air 
passages  may  be  designated  as 
intrapulmonic  pressure.  The 
relations  of  the  two  pressures 
with  reference  to  the  outside 
atmosphere  is  indicated  sche- 
matically in  Fig.  270. 

The  Intrapulmonic  Pres- 
sure and  its  Variations. — The 
air  passages  and  the  alveoli  of 
the  lungs  are  in  free  communi- 
cation with  the  external  air; 
consequently  in  every  position 
of  rest,  whether  at  the  end  of 
inspiration  or  expiration,  the 

.,  ...          .  Fig.     270.— Diagram    to    illustrate   how 

pressure  in  these  cavities  is 
equal  to  that  of  the  atmos- 
phere outside.  During  the  act 
of  inspiration,  however,  the  in- 
trapulmonic pressure  falls  tem- 
porarily below  that  of  the  atmosphere, — that  is,  during  the  inflow  of 
air.  The  extent  to  which  the  pressure  falls  depends  naturally  upon 
the  rapidity  and  amplitude  of  the  inspiratory  movement  and  upon 
the  size  of  the  opening  to  the  exterior.  The  narrowest  portion  of 
the  air  passages  is  the  glottis;  consequently  the  variations  in  pres- 
sure below  this  point  are  probably  greater  than  in  the  pharynx  or 
nasal  cavities.  If  .the  air  passages  are  abnormally  constricted  at 
any  point  the  fall  of  pressure  during  inspiration  will  be  correspond- 

661 


the  pressure  of  the  air  is  exerted  through 
the  lung  walls  upon  the  heart  (//)  and  other 
organs  in  the  mediastinal  space.  The  pres- 
sure on  these  organs  (intrathoracic  pressure) 
is  equal  to  one  atmosphere  minus  the  amount 
of  the  opposing  pressure  exerted  by  the  ex- 
panded lungs. 


662  PHYSIOLOGY    OF    RESPIRATION. 

ingly  magnified  in  the  parts  below  the  constriction,  as  happens,  for 
instance,  in  bronchial  asthma,  edema  of  the  glottis,  cold  in  the 
head,  etc.  Under  normal  conditions  the  fall  of  pressure  during  a 
quiet  inspiration  is  not  large.  Bonders  determined  it  in  man  by 
connecting  a  water  manometer  with  one  nostril  and  found  that  it 
was  equal  to  — 9  or  — 10  mms.  water.  At  the  end  of  an  inspiration, 
if  there  is  a  pause,  the  pressure  within  the  lungs  again  rises,  of  course, 
to  atmospheric.  During  expiration,  on  the  other  hand,  the  collapse 
of  the  chest  wall  takes  place  with  sufficient  rapidity  to  compress  the 
air  somewhat  during  its  escape  and  cause  a  temporary  rise  of  pres- 
sure. In  normal  expiration  Bonders  estimated  this  rise  as  equal  to 
7  or  8  mms.  water.  The  intrapulmonic  pressure  may  vary  greatly 
from  these  figures  in  the  positive  or  negative  direction  according  to 
the  factors  mentioned  above,  especially  the  intensity  of  the  respira- 
tory movement  and  the  size  of  the  opening  to  the  exterior.  The 
extreme  variations  are  obtained  when  the  opening  to  the  outside  is 
entirely  shut  off.  When  an  inspiration  or  an  expiration  is  made 
with  the  glottis  firmly  closed  the  pressure  in  the  lungs,  of  course, 
rises  and  falls  with  the  rarefaction  or  compression  of  the  contained 
air.  A  strong  inspiration  under  such  conditions  may  lower  the 
pressure  by  30  to  80  mms.  of  mercury,  while  a  strong  expiration 
raises  the  pressure  by  an  amount  equal  to  60  to  100  mms.  Hg.  In 
the  act  of  coughing  we  get  such  a  result:  the  strong  spasmodic 
expirations  are  made  with  a  closed  glottis  and  consequently  cause 
a  marked  rise  in  the  intrapulmonic  pressure.  Such  great  varia- 
tions in  pressure  have  a  marked  influence  on  the  flow  of  blood  to 
the  heart.  If,  for  example,  one  maintains  a  strong  expiration 
while  keeping  the  glottis  closed,  the  rise  of  intrapulmonic  and  in- 
trathoracic  pressure  may  be  sufficient  to  clamp  off  the  large  veins 
emptying  into  the  right  auricle. 

Intrathoracic  Pressure. — When  a  reference  is  made  to  the 
pressure  within  the  thorax,  it  is  the  intrathoracic  pressure  that  is 
meant, — that  is,  the  pressure  in  the  pleural  cavity  and  mediastinal 
spaces.  This  pressure,  under  normal  conditions,  is  always  negative, 
— that  is,  is  always  less  than  one  atmosphere.  The  reason  for  this 
is  simply  that  the  lungs  are  distended  to  fill  the  thoracic  cavity,  and 
consequently  the  organs,  like  the  heart,  which  lie  in  this  cavity 
outside  the  lungs,  are  exposed  to  a  pressure  of  one  atmosphere, 
minus  the  force  of  elastic  recoil  of  the  lungs  (see  Fig.  270) .  The  heart 
and  other  intrathoracic  organs  are  protected  from  the  direct  pres- 
sure of  the  air  by  the  thoracic  walls;  they  are  pressed  upon,  how- 
ever, through  the  lungs,  but  naturally  the  atmospheric  pressure  is 
reduced  by  an  amount  equal  to  the  elastic  force  of  the  distended 
lungs.  Intrathoracic  pressure,  in  fact,  may  be  defined  as  intra- 
pulmonic pressure  minus  the  elastic  pull  of  the  lungs,  and  since 
under  usual  conditions  the  intrapulmonic  pressure  is  equal  to  that 


PRESSURE  CONDITIONS  IN  LUNGS  AND  THORAX.  663 

of  the  atmosphere,  the  intrathoracic  pressure  is  less  than  an 
atmosphere  by  an  amount  equal  to  the  recoil  of  the  lungs.  The 
negative  pressure  in  the  thorax  is,  therefore,  equal  to  the  elastic 
force  of  the  lungs,  and  is  larger  the  more  the  lungs  are  put  upon 
a  stretch, — that  is,  the  deeper  the  inspiration.  The  amount  of  this 
negative  pressure  has  been  measured  upon  both  animals  and  men 
by  two  methods :  First  by  Bonder's  method  of  attaching  a  manom- 
eter to  the  trachea  and  then  opening  the  thoracic  walls  so  as  to 
allow  the  atmosphere  to  press  upon  the  exterior  face  of  the  lungs. 
In  this  way  the  elastic  force  of  the  lungs  is  determined,  and,  as 
explained  above,  this  is  equivalent  to  the  negative  pressure.  Second, 
by  thrusting  a  trocar  through  the  thoracic  wall  so  that  its  open  end 
may  lie  in  the  pleural  or  mediastinal  cavity,  the  other  end  being 
appropriately  connected  with  a  manometer.  The  older  observers 
(Hutchinson)  also  made  experiments  upon  freshly  excised  human 
lungs,  determining  their  elastic  force  when  distended  by  known 
amounts  of  air.  The  figures  obtained  by  these  different  methods 
have  shown  some  variations,  but  the  following  quotations  give 
an  idea  of  the  average  extent  of  this  negative  pressure.  Heynsius,* 
making  use  of  the  figures  obtained  by  Hutchinson,  estimates  that 
in  man  the  negative  pressure  in  the  thorax  at  the  end  of  expiration 
is  — 4.5  mms.  Hg,  while  at  the  end  of  an  inspiration  it  is  equal  to 
— 7.5  mms.  Hg, — a  variation  during  respiration,  therefore,  of  3  mms. 
Hg.  That  is,  assuming  that  the  atmospheric  pressure  is  760  mms. 
Hg,  the  conditions  of  pressure  in  the  thorax  and  lungs  at  the  end  of 
inspiration  and  expiration  are  as  follows: 

AT  THE  END  OF  INSPIRATION.       AT  THE  END  OF  EXPIRATION. 
Intrapulmonic  pressure . . .  760    mms.  Hg.  760     mms  Hg. 

Intrathoracic  pressure 752.5     "       "  755.5     "        " 

Aron  gives  results  obtained  from  a  healthy  man  in  whom  a  can- 
nula  was  connected  directly  with  the  pleural  cavity. f  From  36 
determinations  he  obtained  the  average  result  that  at  the  end  of 
quiet  inspiration  the  negative  pressure  is — 4.64  mms.  Hg  and  at 
the  end  of  expiration  — 3.02  mms.  Hg — results  considerably 
lower  than  those  estimated  by  Heynsius.  It  should  be  borne 
in  mind,  however,  that  these  values  depend  upon  the  condition 
of  expansion  of  the  chest, — that  is,  the  position  of  the  body  and 
the  depth  of  inspiration.  On  dogs  Heynsius  reports  as  follows: 
At  end  of  inspiration,  — 9.4  mms.  Hg;  end  of  expiration, — 3.9  mms. 
Hg.  On  rabbits, — 4.5  mms.  and — 2.5  mms.  Hg. 

Variations  of  Intrathoracic  Pressure  with  Forced  and  Unusual 
Respirations. — After  the  most  forcible  expiration,  when  the  air- 

*  "Archiv  f .  die  gesammte  Physiologic, "  29,  265,  1882. 
t  Aron,  quoted  from  Emerson,  "  Johns  Hopkins  Hospital  Reports,"  11, 
194,  1903. 


664  PHYSIOLOGY    OF    RESPIRATION. 

passages  are  open,  the  intrathoracic  pressure  is  still  negative  by  a 
small  amount,  since  the  lungs  are  still  expanded  beyond  what 
might  be  called  their  normal  size, — that  is,  their  size  when  the  pres- 
sure inside  and  outside  is  the  same.  If,  however,  a  forced  expira- 
tion is  made  with  the  glottis  closed,  as  in  the  straining  movements 
of  defecation,  parturition,  etc.,  then  naturally  the  intrathoracic 
pressure  rises  with  the  intrapulmonary  pressure.  The  increased 
pressure  from  the  compressed  air  in  the  lungs  is  felt  upon  the  organs 
in  the  mediastinal  spaces.  The  large  veins  especially  are  affected, 
and  the  flow  in  them  is  partially  blocked,  as  is  shown  by  the  swelling 
of  the  veins  in  the  neck  outside  the  thorax.  The  maintenance  of 
such  conditions  for  a  considerable  period  may  seriously  affect  the 
circulation.  The  same  general  effect  is  obtained  also  in  attacks  of 
coughing,  the  violent  spasmodic  expirations  with  closed  glottis 
causing  a  visible  venous  congestion  in  the  head  from  the  obstruction 
to  the  venous  flow  into  the  heart.  Forcible  inspirations,  on  the 
other  hand,  lower  the  intrathoracic  pressure — that  is,  increase  the 
negativity — whether  the  glottis  is  open  or  closed.  When  the  glottis 
is  freely  open  and  a  deep  inspiration  is  made  the  intrathoracic 
pressure  may  fall  as  much  as  30  mms.  Hg, — that  is,  become  equal 
to  730  mms.  The  lungs  being  much  more  expanded  exert  a  corre- 
spondingly greater  elastic  force.  If  the  glottis  is  closed  during  a 
deep  inspiration  then  there  is  little  actual  expansion  of  the  lungs, 
but  the  intrapulmonary  pressure  falls  from  the  rarefaction  of  the  air 
in  the  lungs,  and  the  intrathoracic  pressure,  of  course,  falls  with  it. 
The  Origin  of  the  Negative  Pressure  in  the  Thorax. — As  is  evi- 
dent from  the  above  explanation,  the  fact  that  the  pressure  in  the 
thorax  is  less  than  an  atmosphere  is  due  in  the  long  run  to  the 
circumstance  that  the  lungs  are  smaller  than  the  thoracic  cavity, 
which  they  occupy.  In  the  fetus  the  lungs  are  solid,  and  completely 
fill  the  thoracic  cavity,  except  for  the  part  occupied  by  the  other 
organs.  It  has  been  a  question  whether  after  birth  the  size  of  the 
thoracic  cavity  is  suddenly  and  permanently  increased  by  the  first 
inspiratory  movements,  and  a  negative  intrathoracic  pressure  thus 
produced  at  once.  The  careful  experiments  of  Hermann*  seem  to 
have  settled  this  point.  He  proved  that  newly-born  children 
between  the  first  and  the  fourth  day,  show  no  measurable  negative 
pressure  in  the  thorax,  and  at  the  eighth  day  the  pressure  in  the 
thoracic  cavity  is  less  than  atmospheric  by  an  amount  equal  to  only 
— 0.4  mm.  Hg.  The  negative  pressure  as  we  find  it  in  the  adult  is 
evidently  developed  gradually,  and  is  due  to  the  fact  that  the 
thorax  increases  in  size  more  rapidly  and  to  a  greater  extent  than 
the  lungs,  so  that  to  fill  the  cavity  the  lungs  become  more  and  more 
expanded.  It  follows,  also,  from  these  facts,  that  the  new-born 
*  Hermann,  "  Archiv  f.  d.  gesammte  Physiologic,"  30,  276, 1883. 


V 


PRESSURE  CONDITIONS  IN  LUNGS  AND  THORAX.  665 

child  has  practically  no  reserve  supply  of  air  in  the  lungs;  at  each 
expiration  the  lungs  are  entirely  emptied  (except  for  the  minimal 
air).  The  ventilation  of  the  lung  alveoli  is  correspondingly  more 
perfect  than  in  older  persons. 

Pneumothorax. — When  the  pleural  cavity  on  either  side  is  opened 
by  any  means  air  enters  and  causes  a  greater  or  less  shrinkage  of 
the  corresponding  lung.  This  condition  of  air  within  the  pleural 
cavity  is  designated  as  pneumothorax.  It  is  evident  that  air  may 
enter  the  pleural  cavity  in  one  of  two  general  ways:  By  a  puncture 
of  the  parietal  pleura  such  as  may  be  made  by  gunshot  or  stab 
wounds  in  the  chest,  or  by  a  puncture  of  the  visceral  pleura,  such  as 
may  occur,  for  example,  by  the  rupture  of  a  tubercle  in  pulmonary 
tuberculosis,  the  air  in  this  case  entering  from  the  alveoli  of  the 
lungs.  From  the  physical  conditions  involved  it  is  evident 
that  if  the  opening  into  the  pleural  cavity  is  kept  patent  then  the 
lung  will  collapse  completely  and  eventually  will  become  entirely 
solid,  since  the  small  amount  of  entrapped  minimal  air  will  be 
absorbed  by  the  blood.  The  other  lung,  the  heart,  etc..,  will  also 
be  displaced  somewhat  from  their  normal  position  by  the  unusual 
pressure.  If,  however,  the  opening  is  closed,  then  the  air  in  the 
pleural  cavity  may  be  absorbed  completely  by  the  circulating  blood 
and  the  lung  again  expand  as  this  absorption  takes  place.  In 
human  beings  pneumothorax  occurs  most  frequently  in  conditions 
of  disease,  particularly  pulmonary  tuberculosis,  and  the  air  in  the 
thorax  is  associated  also  with  a  liquid  effusion,  this  combination 
being  designated  sometimes  as  hydropneumothorax.* 

The  Aspiratory  Action  of  the  Thorax. — The  negative  pres- 
sure prevailing  in  the  thoracic  cavity  must  affect  the  organs  in  the 
mediastinal  space.  The  intrathoracic  portion  of  the  esophagus, 
for  instance,  is  exposed,  at  times  of  swallowing  at  least,  to  a  full 
atmosphere  of  pressure  on  its  interior,  while  on  its  exterior  it  is  under 
the  diminished  intrathoracic  pressure.  This  difference  tends  to 
dilate  the  tube  and  may  aid  in  the  act  of  swallowing.  The  main- 
effect  of  the  difference  in  pressure  is  felt,  however,  upon  the  flow 
of  lymph  and  blood,  especially  the  latter.  The  large  veins  in  the 
neck  and  axilla  are  under  the  pressure  of  an  atmosphere  exerted 
through  the  skin,  and  the  same  is  true  for  the  inferior  cava  in  the 
abdomen.  But  the  superior  and  inferior  cavse  and  the  right  auricle 
are  under  a  pressure  less  than  one  atmosphere.  This  difference  in 
pressure  must  act  as  a  constant  favoring  condition  to  the  flow  of 
blood  to  the  heart.  The  difference  is  markedly  increased  at  each 
inspiration;  so  that  at  each  such  act  there  is  an  increase  in  the 
velocity  and  volume  of  the  flow  to  the  heart, — an  effect  which  is 

*  See  Emerson.  "Pneumothorax."  Johns  Hopkins  Hospital  Reports. 
11,  1,  1903. 


666  PHYSIOLOGY    OF    RESPIRATION. 

usually  referred  to  as  the  aspiratory  action  of  the  thorax.  At  each 
inspiration  blood  is  "  sucked  "  from  the  extrathoracic  into  the  intra- 
thoracic  veins.  So  far  as  the  inferior  cava  is  concerned,  this  effect 
is  augmented  by  the  simultaneous  increase  in  abdominal  pressure. 
For  as  the  diaphragm  descends  it  raises  the  pressure  in  the  ab- 
domen as  it  lowers  the  pressure  in  the  thorax.  The  two  fac- 
tors co-operate  in  forcing  more  blood  from  the  abdominal  to  the 
thoracic  portion  of  the  cava.  This  aspiratory  effect  upon  the  ven- 
ous flow  to  the  heart  is  made  more  important  by  the  arrangement 
of  the  valves  in  the  jugular,  subclavian,  and  femoral  veins,  which,  as 
explained  on  p.  520  facilitate  the  emptying  of  the  venous  cis- 
tern toward  the  heart.  There  should  be,  of  course,  a  similar 
effect,  but  in  thesopposite  direction,  upon  the  flow  in  the  arter- 
ies. Each  inspiration  should  retard  the  arterial  outflow  from 
the  aorta  into  its  extrathoracic  branches.  As  a  matter  of  fact,  this 
effect  probably  does  not  take  place.  The  arteries  are  thick  walled 
and  are -distended  by  a  high  internal  pressure,  so  that  the  small 
change  of  pressure  of  three  or  four  millimeters  of  mercury  during 
inspiration  is  probably  incapable  of  influencing  the  caliber  of  the 
arteries,  while  it  has  a  distinct  effect  upon  the  thin-walled  veins, 
whose  internal  pressure  is  very  small.  The  changes  in  intra- 
thoracic  pressure  during  respiration  must  affect  the  blood-flow  also 
in  the  pulmonary  circuit,  the  flow  from  the  right  to  the  left  side  of 
the  heart.  This  effect  is  manifested  in  the  so-called  respiratory 
waves  of  blood-pressure  which  may  be  discussed  briefly  in  this 
connection. 

Respiratory  Waves  of  Blood-pressure. — When  a  record  is 
taken  of  the  blood-pressure  the  tracing  shows  waves,  unless  the 
respiratory  movements  are  very  shallow,  which  are  synchronous  with 
the  respiratory  movements  (see  Fig.  271).  When  the  respiration 
is  dyspneic  the  waves  of  pressure  are  very  marked.  To  ascertain  the 
exact  relations  of  these  variations  to  the  phases  of  respiration  it  is 
necessary  to  make  simultaneous  tracings  of  blood-pressure  and 
respiration  movements  with  the  recording  pens  properly  superposed. 
In  the  dog  it  is  usually  stated  that  the  blood-pressure  falls  slightly 
at  the  beginning  of  inspiration,  but  rises  during  the  rest  of  the 
act.  At  the  beginning  of  expiration  the  pressure  continues  to 
rise  for  a  time  and  then  falls  during  most  of  this  phase.  On  the 
whole,  therefore,  the  effect  of  inspiration,  its  final  effect,  is  to  cause 
a  rise  of  arterial  pressure,  while  the  effect  of  expiration  is  to  cause 
a  fall.  The  relationship  of  the  two  curves  varies  in  other  animals, 
so  that  a  general  statement  regarding  the  relationship  between  the 
phase  of  respiration  and  the  change  in  blood-pressure  cannot  be 
made.  In  the  case  of  man  various  methods  have  been  employed 
to  determine  this  relationship.  A  continuous  record  of  blood- 
pressure  in  man  may  be  taken  by  means  of  the  sphygmomanometer 


PRESSURE    CONDITIONS    IN    LUNGS    AND    THORAX.  667 

according  to  a  principle  first  suggested  by  Erlanger.  The  principle 
involved  is  to  set  the  pressure  in  the  cuff  on  the  outside  of  the  arm, 
somewhat  below  systolic  pressure.  The  pulsations  in  the  man- 
ometer will  therefore  be  submaximal  (see  p.  504).  If  now  the  blood 
pressure  rises  the  amplitude  of  the  pulsations  will  increase,  since  the 


Fig.  271. — Respiratory  waves  of  blood-pressure.  Typical  blood-pressure  record  as 
taken  with  a  mercury  manometer:  Bp  the  blood-pressure  record,  shows  the  separate 
heart  beats  and  the  larger  respiratory  waves,  each  of  which  comprises  six  to  seven  heart 
beats. 

intra-arterial  diastolic  pressure  thereby  approaches  the  extra- 
arterial  pressure.  The  reverse  of  course  happens  with  a  fall  of 
blood-pressure.  Making  use  of  this  method  it  is  found*  that  in 
some  cases  in  man  the  blood-pressure  falls  during  inspiration  and 
rises  during  expiration,  while  in  other  cases  the  reverse  relation- 
ship holds.  The  cause  for  this  difference  is  explained  below. 

It  is  generally  agreed  that  the  effect  of  the  respiratory 
movements  on  the  arterial  pressure  is  due  mainly  to  mechanical 
factors  which  influence  the  amount  of  blood  discharged  into  the 
aorta.  The  matter  is  difficult  to  analyze  successfully,!  but  the 

*  Erlanger  and  Festerling,  "Journal  of  Experimental  Medicine,"  15,  370, 
1912;  also  Snyder,  "American  Journal  of  Physiology,"  36,  430,  1915. 

fFor  the  older  literature,  see  de  Jager,  "Journal  of  Physiology,"  7,  130. 


668  PHYSIOLOGY    OF    RESPIRATION. 

following  factors  are  the  ones  which  have  usually  been  emphasized. 
At  each  inspiration  the  aspiratory  action  of  the  thorax  upon  the 
venous  flow  to  the  right  side  of  the  heart  is  increased,  and  con- 
sequently more  blood  is  thrown  into  the  pulmonary  circulation 
and  eventually  into  the  left  ventricle.  This  factor  would  tend  to 
increase  the  output  of  the  heart  during  inspiration  and  thereby 
raise  arterial  pressure.  On  the  other  hand  the  blood-capacity 
of  the  lungs  is  increased  during  inspiration,  owing  to  a  stretching 
of  the  blood-capillaries  during  the  expansion  of  the  lungs,  and  this 
increase  in  capacity  may  serve,  temporarily  at  least,  to  hold  back 
the  flow  of  blood  to  the  left  ventricle  and  thereby  cause  a  fall  of 
pressure  during  the  inspiration.  So  far  as  these  factors  are  con- 
cerned, it  is  evident  that  the  permanent  resultant  effect  should  be 
in  the  direction  of  an  increased  flow  of  blood  into  the  aorta  and  a 
rise  of  aortic  pressure  as  a  result  of  inspiration,  but  the  time 
relations  of  this  rise  of  pressure  may  be  obscured  or  reversed  by  the 
temporary  retarding  effect  of  the  increase  in  the  capacity  of  the 
capillary  bed  in  the  lungs  at  the  beginning  of  inspiration.  There  is 
an  additional  factor,  however,  whose  influence  is  more  evident  as 
regards  the  time  relation  between  the  rise  of  aortic  pressure  and 
the  phase  of  respiration.  This  factor  is  a  change  in  heart-rate 
caused  by  the  inspiration. 

In  some  individuals  the  heart-rate  increases  very  perceptibly 
during  inspiration,  the  change  in  rate  taking  place  quite  promptly 
with  the  beginning  of  the  inspiratory  act.  In  others  this  phe- 
nomenon is  less  marked,  or  is  absent  altogether.  It  has  been 
shown  by  Fredericq  that  this  change  in  dogs  occurs  when  the  chest 
is  widely  opened  and  the  respiratory  movements  can  have  no 
mechanical  effect  upon  the  heart.  He  suggests,  therefore,  that  the 
accelerated  pulse  during  inspiration  is  due  to  an  associated  activity 
in  the  nerve  centers  of  the  medulla.  When  the  inspiratory  center 
discharges  its  efferent  impulses  into  the  phrenic  nerves  it  also 
sends  impulses  by  a  sort  of  overflow  into  the  neighboring  cardio- 
inhibitory  center.  This  latter  center  is,  thereby,  partially  in- 
hibited, its  tonic  effect  on  the  heart  is  diminished,  and  the  rate  of 
the  heart  is  increased.  The  variability  in  this  factor  in  different 
individuals  may  help  to  explain  the  fact  that  in  some  cases  the 
rise  in  blood-pressure  occurs  during  the  phase  of  inspiration,  while 
in  others  it  coincides  rather  with  the  expiration.  It  is  observed, 
at  least,  that  in  cases  showing  an  inspiratory  rise  of  pressure  there 
is  also  a  marked  inspiratory  acceleration  of  the  heart-rate,  while 
in  those  cases  where  there  is  an  inspiratory  fall  of  pressure  the 
effect  of  the  inspiration  on  the  heart-rate  is  absent  or  small,  t 

*  Snyder,  loc.  cit..,  and  Foley,  Coblentz,  and  Snyder,  "American  Journal 
of  Physiology,"  40,  554,  1916. 


CHAPTER  XXXVI. 

THE    CHEMICAL  AND    PHYSICAL    CHANGES    IN    THE 
AIR  AND  THE  BLOOD  CAUSED  BY  RESPIRATION. 

The  Inspired  and  the  Expired  Air. — The  inspired  air,  atmos- 
pheric air,  varies  in  composition  in  different  places.  The  essential 
constituents  from  a  physiological  standpoint  are  the  oxygen, 
nitrogen,  and  carbon  dioxid.  The  new  elements — argon,  krypton, 
etc. — have  not  been  shown  to  have  any  physiological  significance, 
and  are  included  with  the  nitrogen.  The  accidental  constituents 
of  the  air  vary  with  the  locality.  In  average  figures,  the  composi- 
tion of  this  air  is,  in  volume  per  cent.:  nitrogen,  79;  oxygen,  20.96; 
carbon  dioxid,  0.04.  The  expired  air  varies  in  composition  with 
the  depth  of  the  expiration  and,  of  course,  with  the  composition  of 
the  air  inspired.  Under  normal  conditions  the  expired  air  contains, 
in  volume  per  cent. :  nitrogen,  79;  oxygen,  16.02;  carbon  dioxid, 
4.38.  In  passing  once  into  the  lungs  the  air,  therefore,  gains  4.34 
volumes  of  carbon  dioxid  to  each  hundred,  and  loses  4.94  volumes 
of  oxygen. 

N.  O.  C02. 

Inspired 79  20.96  0.04 

Expired 79  16.02  4.38 

4.94  4.34 

This  table  expresses  the  main  fact  of  external  respiration:  the 
respired  air  loses  oxygen  and  gains  carbon  dioxid  and  consequently 
the  blood  absorbs  oxygen  and  eliminates  carbon  dioxid.  It  will  be 
noted,  also,  that  the  volume  of  oxygen  absorbed  is  greater  than  the 
volume  of  carbon  dioxid  given  off.  This  discrepancy  is  explained 
by  the  general  fact  that  the  oxygen  absorbed  is  used  in  the  long  run 
to  oxidize  the  carbon  and  also  the  hydrogen  of  the  food;  conse- 
quently, while  most  of  it  is  eliminated  in  the  expired  air  as  carbon 
dioxid,  some  of  it  is  excreted  as  water.  For  the  sake  of  complete- 
ness it  may  be  stated  that  traces  of  hydrogen  and  methane  are  also 
found  in  the  expired  air.  They  probably  originate  in  the  intestines 
from  fermentation  processes  and  are  carried  off  in  solution  in  the 
blood. 

669* 


670  PHYSIOLOGY    OF    RESPIRATION. 

Physical  Changes  in  the  Expired  Air. — The  expired  air  is 
warmed  nearly  or  quite  to  the  body  temperature  and  is  nearly 
saturated  with  water  vapor.  Since,  as  a  rule,  the  air  that  we 
inspire  is  much  cooler  than  the  body  and  is  far  from  being  saturated 
with  water  vapor,  it  is  evident  that  the  act  of  respiration  entails 
upon  the  body  a  loss  of  heat  and  of  water.  Breathing  is,  in  fact, 
one  of  the  means  by  which  the  body  temperature  is  regulated, 
although  in  man  it  is  a  subsidiary  means.  In  other  animals — the 
dog,  for  instance — panting  is  a  very  important  aid  in  controlling  the 
body  heat.  Heat  is  lost  in  respiration  not  simply  in  warming  the 
air  in  the  air  passages,  but  also  by  the  evaporation  of  water  in  the 
alveoli,  the  conversion  of  water  from  the  liquid  to  the  gaseous  form 
being  attended  by  an  absorption  of  heat.  Breathing  is  also  one 
of  the  means  by  which  the  water  contents  of  the  body  are  regulated. 
The  water  that  we  ingest  or  that  is  formed  within  the  body  is  kept 
within  certain  limits,  and  this  regulation  is  effected  by  the  secretions 
of  urine  and  sweat  mainly,  but  in  part  also  by  the  constant  loss  of 
water  from  the  blood  as  it  passes  through  the  lungs. 

The  Injurious  Effect  of  Breathing  Expired  Air — Ventila- 
tion.— It  is  generally  recognized  that  in  badly  ventilated  rooms  the 
air  acquires  a  disagreeable  odor,  perceptible  especially  immediately 
on  entering,  and  that  persons  remaining  under  such  conditions  for 
any  length  of  time  suffer  from  headache,  depression,  and  a  general 
feeling  of  uncomfortableness.  It  has  been  assumed,  although 
without  sufficient  proof,  that  these  effects  are  due  to  the  vitiation  of 
the  atmosphere  by  the  expired  air.  When  the  ventilation  is  very 
imperfect  and  the  room  greatly  crowded  death  may  result,  as,  for 
instance,  in  the  historical  case  of  the  Black  Hole  of  Calcutta.  In 
extreme  cases  of  this  latter  kind  it  is  most  probable  that  several 
causes  combine  to  produce  a  fatal  result.  The  conditions  are  such 
as  to  lead  to  a  very  large  increase  in  carbon  dioxid  and  diminution 
of  oxygen  in  the  respired  air — a  result  which  carried  to  a  certain 
point  will  itself  cause  death;  and  in  addition  the  air  becomes 
heated  to  a  high  temperature  and  saturated  with  water  vapor, 
both  of  these  latter  conditions  preventing  loss  of  heat  from 
the  body  and  producing  a  fever  temperature.  Under  the  or- 
dinary conditions  of  life  poor  ventilation  produces  its  ob- 
viously evil  results  in  rooms  temporarily  occupied — schools, 
churches,  lecture  rooms,  theaters,  etc., — and  it  is  important  to  know 
what  is  the  cause,  and  how  it  may  be  avoided.  On  the  basis  of  older 
Work  it  has  been  assumed  that  there  is  present  in  the  expired  air  a 
volatile  organic  substance  which  when  breathed  again,  possibly  after 
having  undergone  some  further  change,  exerts  a  toxic  influence.  The 
evil  effects  of  badly  ventilated  rooms  have  been  attributed  mainly 


CHANGES    IN    AIR    AND    BLOOD    IN    RESPIRATION.  671 

to  this  supposed  substance.  The  investigations  that  have  been 
made  upon  this  substance  are,  unfortunately,  far  from  being 
conclusive.*  It  seems  to  be  clear  that,  when  the  expired  air  is 
condensed  by  passing  it  into  a  cooled  chamber,  the  water  thus 
obtained,  about  100  c.c.  for  2500  liters  of  air,  is  clear,  odorless,  and 
has  only  a  minute  trace  of  organic  matter.  If  this  liquid  with  or 
without  condensation  is  injected  under  the  skin  or  into  the  blood- 
vessels no  evil  result  follows,  according  to  the  testimony  of  the 
majority  of  observers.  But  it  remains  possible,  of  course,  that  the 
substance  if  present  may  be  destroyed  by  this  method  or  may  es- 
cape precipitation  in  the  condensed  water.  An  experiment  that 
was  supposed  to  give  a  positive  indication  of  the  existence  of  an 
organic  (basic)  poison  in  the  expired  air  is  the  following,  first  per- 
formed by  Brown-Sequard :  A  series  of — say,  five — bottles,  each 
of  a  capacity  of  a  liter  or  more,  are  connected  together  in  train  so 
that  air  can  be  drawn  through  them  by  an  aspirator.  A  live 
mouse  is  placed  in  each  bottle,  and  between  bottles  4  and  5  an 
absorption  tube  is  arranged  containing  sulphuric  acid.  Under 
these  conditions  only  the  mouse  in  bottle  1  gets  fresh  air,  those  in 
the  successive  bottles  get  more  and  more  impure  air,  while  in  bottle 
5  this  air  is  purified  to  the  extent  of  removing  the  organic  matter 
by  passing  it  through  sulphuric  acid.  The  result  of  such  an  ex- 
periment as  described  by  some  observers  is  that  the  mouse  in  bottle 
4  dies  after  a  certain  number  of  hours,  the  one  in  bottle  3  later, 
while  those  in  the  first  and  last  bottles  show  no  injurious  effects. 
The  obvious  conclusion  is  that  death  in  such  cases  is  due  to  some 
organic  toxic  substance,  and  not  to  a  mere  increase  of  carbon 
dioxid,  chemical  analysis  showing  that  this  latter  substance  does 
not  accumulate  sufficiently  under  these  conditions  to  cause  a  fatal 
result.  Some  other  observers  have  failed  to  get  this  effect,  but 
even  assuming  it  to  be  correct  it  will  be  noted  that  the  experiment 
gives  no  proof  that  the  organic  substance  in  question  is  excreted 
in  the  expired  air.  Indeed,  the  seemingly  very  careful  experiments 
of  Formanek  make  it  probable  that  in  these  experiments  the  toxic 
substance  is  ammonia  or  an  ammonia  compound,  which  is  not 
given  off  from  the  lungs,  but  from  the  decomposition  of  the  urine 
and  feces  in  the  cage.  When  this  latter  source  of  contamination 
is  removed  the  expired  air  is  practically  free  from  ammonia  and 
without  injurious  effect.  The  expired  air,  therefore,  according  to 
work  of  this  character,  contains  no  organic  poison  which  can  be 

*  See  Haldane  and  Smith, 
1,  168,  and  318  1893 
"Archiv  f.  Hygiene,"  „<_,,  .., 
"  Journal  of  Exp.  Medicine,"  17,  132,  1913. 


672  PHYSIOLOGY    OF    RESPIRATION. 

regarded  as  a  product  of  respiration,  and  this  conclusion  is  sup- 
ported in  a  general  way  by  the  experience  that  air  can  be  rebreathed 
safely  an  indefinite  number  of  times  provided  the  excess  of  CO2  is 
removed  by  absorption  and  new  oxygen  is  supplied  to  replace  that 
used  up  in  the  body. 

Some  observers  (Hermann,  Haldane,  and  Smith)  have  made 
direct  experiments  upon  men  which  also  throw  much  doubt  upon 
the  existence  of  a  toxic  substance  in  expired  air.  Individuals 
kept  in  a  confined  space  for  a  number  of  hours  show  no  evil  effects, 
provided  they  are  not  doing  muscular  work,  except  when  the  ac- 
cumulation of  the  carbon  dioxid  has  reached  a  concentration  of 
over  4  per  cent.  At  this  concentration  rapid  breathing  is  apparent, 
and  if  it  rises  to  10  per  cent,  great  distress  is  felt  and  the  face  be- 
comes congested  and  blue.  These  authors  conclude  that  expired 
air  is  injurious  in  itself  only  from  the  carbon  dioxid  it  contains,  and 
only  when  this  gas  accumulates  to  a  percentage  such  as  is  not  found 
in  the  worst  ventilated  rooms.*  As  opposed  to  these  negative 
results,  Weichardt  reports  a  series  of  experiments  upon  mice  in 
which  the  expired  air  of  a  number  of  animals  was  passed  through 
acidulated  water,  and  the  latter  was  then  condensed  in  a  vacuum  to 
a  small  volume  and  neutralized.  When  injected  into  a  fresh  ani- 
mal this  material  brought  on  a  soporific  condition,  fall  of  body  tem- 
perature, and  diminution  in  output  of  carbon  dioxid.  The  author 
explains  these  results  on  the  assumption  that  some  of  the  so-called 
fatigue-toxin  (kenotoxin)  is  excreted  by  way  of  the  lungs,  and  he  be- 
lieves that  the  known  depressing  effects  of  poor  ventilation  are  an 
expression  of  the  action  of  this  substance.  His  results  have  not 
been  confirmed  and,  at  present,  the  definitely  known  evil  results 
of  breathing  the  air  of  crowded,  poorly  ventilated  rooms  must  be 
referred  to  other  causes,  such  as  the  increase  in  temperature  and 
moisture.  These  two  conditions  cause  depression  and  malaise 
even  when  an  adequate  supply  of  air  is  provided.  If  the  ventila- 
tion is  so  poor  that  the  carbon  dioxid  accumulates  to  the  extent 
of  3  to  4  per  cent.,  then  this  factor  begins  to  exercise  a  direct  effect 
upon  the  respiratory  movements  and  the  general  condition, — an 
effect  which  increases  as  the  percentage  of  carbon  dioxid  rises  (see 
p.  703). 

Ventilation. — It  is  obvious  from  the  foregoing  statements  that 
our  knowledge  is  not  yet  sufficiently  complete  to  enable  us  to  say 
positively  at  what  point  air  in  a  room  becomes  injurious  to  breathe, 
whether  from  products  of  expiration,  or,  according  to  recent  views, 
from  changes  in  temperature  and  moisture.  The  statement  was 

*  See  Hill,  et  al.,  "Smithsonian  Miscellaneous  Collections,"  vol.  60,  No. 
23,  1913. 


CHANGES    IN   AIR   AND    BLOOD    IN    RESPIRATION.  673 

formerly  made  in  the  books  that,  when  the  air  contains  as  much  as 
1  per  cent,  of  carbon  dioxid  (Smith)  that  has  been  produced  by 
breathing,  evil  results,  as  judged  by  one's  feelings,  are  sure  to  occur, 
but  this  statement  was  founded  on  the  belief  that  an  organic  poison 
is  present  in  expired  air.  As  we  have  seen,  modern  investigations 
have  made  this. belief  improbable,  and  have  shown  that  CO2  in 
expired  air  in  concentrations  of  1  per  cent,  exerts  no  injurious  effect 
except  possibly  under  conditions  requiring  much  muscular  exertion. 
Under  sedentary  conditions  such  as  need  to  be  considered  usually  in 
problems  of  ventilation,  the  important  factors  to  be  borne  in  mind 
are  the  temperature,  moisture,  movement,  and  sweetness  of  the  air. 
In  crowded  rooms  the  exhalations  from  the  body  may  occasion  a 
disagreeable  odor  which  is  offensive,  although  so  far  as  known  not 
physically  injurious.  The  renewal  of  air  must  be  adequate  to  pre- 
vent the  noticeable  accumulation  of  these  volatile  products,  and  if 
the  air  is  recirculated  these  substances  should  be  removed  by  a  sys- 
tem of  washing.  The  essential  factors  to  be  considered  in  ventila- 
tion are,  however,  the  temperature  and  degree  of  moisture.  When 
these  factors  are  allowed  to  increase  they  soon  produce  a  condition 
of  listlessness  and  discomfort.  The  reason  for  this  effect  has 
not  been  studied  with  sufficient  care,  but  possibly  it  is  connected 
with  some  derangement  of  the  temperature-regulating  mechanisms 
of  the  body.  In  accordance  with  this  view  it  is  found  by  experi- 
ment, and  indeed,  it  is  a  matter  of  every-day  experience,  that  when 
the  air  is  kept  in  movement,  by  fans,  for  example,  the  ill  effects  of  a 
warm  and  stuffy  room  are  greatly  lessened.  The  moving  air  by 
accelerating  the  evaporation  of  the  perspiration  of  the  skin  in- 
creases the  loss  of  heat  from  the  body  (see  Chapter  LI).  To  ensure 
physical  comfort  and  mental  efficiency  the  ventilation  of  crowded 
rooms  must  be  sufficient  to  keep  the  degree  of  temperature  and 
moisture  within  certain  limits  the  range  of  which  must  be  deter- 
mined by  actual  experiments.  Experiments  of  this  character  made 
in  this  country  indicate  that  the  optimal  conditions  approximate 
a  temperature  of  65°  to  70°  F.  and  a  relative  humidity  of  50  to  60 
per  cent.  When  the  new  air  is  taken  from  the  outside,  arrange- 
ments should  be  provided  to  heat  and  moisten  it,  or  to  cool  and  dry 
it,  according  to  conditions,  and  to  regulate  the  flow  of  air  in  accord- 
ance with  the  number  of  persons  and  the  volume  of  the  enclosed 
space.  The  amount  of  cubic  space  allotted  to  each  individual  will 
vary  naturally  according  to  the  rate  of  renewal  or  movement  of  the 
air.  The  older  estimate  of  30  cubic  feet  per  minute  to  each  person 
may  be  reduced  with  safety  to  as  little  as  15  cubic  feet  per  person, 
provided  the  movement  of  air  is  adequate.*  Since  the  idea  of  an 

*  See  Larson,  "Transactions  of  American  Society  of  Heating  and  Ventilat- 
ing Engineers,"  1916,  vol.  22,  p.  11. 

43 


674 


PHYSIOLOGY    OF    RESPIRATION. 


organic  poison  in  the  expired  air  has  been  abandoned  it  has  been 
found  feasible  to  recirculate  the  air  in  buildings  by  installing  proper 
arrangements  for  washing  it  and  controlling  its  temperature  and 
moisture.  In  cold  weather  a  system  of  this  kind  reduces  consider- 
ably the  cost  of  heating. 


Fig.  272.-^-Gas  pump  for  extracting  the  gases  of  blood  (Grehanf):  M  and  F,  Mercury 
receivers;  P,  windlass  for  raising  and  lowering  M;  m,  a  three-way  stop-cock  protected  by  a 
seal  of  mercury  or  water;  C,  a  cup  with  mercury  over  which  the  receiving  eudiometer  is 

S  laced  to  collect  the  gases;  B,  the  bulb  in  which,  after  a  vacuum  is  made,  the  blood  is  intro- 
uced  by  the  graduated  syringe,  S.  By  means  of  the  stop-cock  m  the  vacuum  in  F,  caused  by 
the  fall  of  the  mercury,  can  be  placed  in  communication  with  B.  After  the  gases  have  diffused 
over  into  F ,  M  is  raised,  and  when  the  stop-cock  m  is  properly  turned  these  gases  are  driven 
out  through  C  into  the  receiving  tube.  The  operation  is  repeated  until  no  more  gas  is  given 
off  from  B. 

The  Gases  of  the  Blood. — The  gases  that  are  contained  in  the 
blood  are  oxygen,  carbon  dioxid,  and  nitrogen.  These  gases  may 
be  extracted  completely  and  in  a  condition  for  quantitative  analysis 
by  means  of  some  form  of  gas-pump.  The  principle  of  most  of  the 
gas-pumps  used  in  the  physiological  laboratories  is  the  same.  The 


CHANGES    IN   AIR    AND    BLOOD    IN    RESPIRATION.  675 

apparatus  is  arranged  so  that  the  blood  to  be  examined  is  brought 
into  a  vacuum  while  kept  at  the  temperature  of  the  body.  Under 
these  conditions  all  of  the  oxygen  and  nitrogen  and  part  of  the  car- 
bon dioxid  are  given  off  and  may  be  collected  by  suitable  means. 
A  portion  of  the  carbon  dioxid  present  in  the  blood  is  in  such  stable 
combination  that  to  remove  it  it  may  be  necessary  to  add  some 
dilute  acid,  such  as  phosphoric  acid.  This  portion  of  the  carbon 
dioxid  is  designated  in  this  connection  as  the  fixed  carbon  dioxid. 

The  principle  of  the  gas  pump  may  be  explained  most  easily  by  describing 
the  simple  £91™  devised  by  Grehant.  The  essential  parts  of  this  pump  are 
represented  in  Figure  272.  The  mercury  pump  consists  of  two  bulbs,  one 
movable  (M),  the  other  fixed  (F).  M  may  be  raised  and  lowered  by  the  wind- 
lass (P) .  Above  F,  there  is  a  three-way  stopcock  (m)  by  means  of  which  the 
chamber  F  may  be  put  into  communication  with  the  outside  air  by  way  of  C, 
or  with  the  bulb  B,  which  is  to  contain  the  blood,  or  may  be  shut  off  com- 
pletely. If  M  is  raised  so  as  to  fill  F  entirely,  and  the  stopcock  ra  is  shut  off, 
then  on  lowering  M  the  mercury  will  flow  into  it,  leaving  a  perfect  vacuum 
in  F,  since  the  distance  between  F  and  M  is  greater  than  the  barometric 
height.  If  the  stopcock  m  is  turned  so  as  to  throw  F  into  communication 
with  B,  the  chamber  of  this  latter  is  brought  under  the  influence  of  the  vac- 
uum and  any  gases  that  it  may  contain  will  be  distributed  between  B  and 
F.  If  stopcock  m  is  again  turned  off  and  M  is  raised,  the  gases  in  F  will  be 
condensed  at  its  upper  end,  and  by  turning  the  stopcock  m  properly  these 
gases  may  be  forced  to  the  outside  by  way  of  C  or  may  be  collected,  if  de- 
sired, in  a  burette  filled  with  mercury  and  inverted  over  the  opening  from 
F  contained  in  the  bottom  of  C.  In  performing  an  experiment  the  flask 
B,  which  is  to  contain  the  blood,  is  connected  with  F,  as  shown  in  the  figure, 
all  joints  being  protected  from  leakage  by  a  seal  of  water  outside,  as  shown 
at  h,  which  represents  a  piece  of  wide  rubber  tubing  filled  with  water  so  as 
to  protect  a  joint  between  two  pieces  of  glass  tubing.  B  is  next  exhausted 
completely  by  raising  and  lowering  M  a  number  of  times  in  the  way  described 
above  until  on  throwing  B  into  communication  with  a  vacuum  in  F  no  further 
gas  is  given  off.  The  last  particles  of  air  may  be  driven  out  from  B  by  boil- 
ing a  little  water  in  it.  After  a  complete  vacuum  has  been  established  in  B 
a  measured  amount  of  blood  is  introduced  from  a  graduated  syringe,  S,  as 
represented  in  the  figure.  This  blood  must  be  taken  directly  from  the  vessels 
of  the  animal  and  be  introduced  into  B  at  once.  B  is  kept  immersed  in  water 
at  the  temperature  of  the  body,  and  the  bulb  M  is  now  raised  and  lowered  a 
number  of  times  so  that  the  gases  given  off  from  the  blood  are  drawn  over 
into  F  and  then  by  proper  manipulation  of  the  stop-cock  are  driven  into 
a  burette  fastened  over  the  opening  of  the  tube  in  C.  To  drive  off  all  of  the 
carbon  dioxid  a  little  dilute  phosphoric  acid  must  be  added  to  the  blood  in 
B  by  means  of  the  syringe,  S.  The  gases  thus  collected  into  the  burette  are 
first  measured  and  are  then  analyzed  for  the  three  important  constituents 
by  some  of  the  accepted  gasometric  methods.  The  principle  involved  is  to 
absorb  first  from  the  mixture  all  of  the  CO2  by  introducing  a  solution  of  sodium 
or  potassium  hydrate.  The  reading  of  the  volume  left  after  this  absorption 
is  completed  compared  with  the  first  reading  gives  the  volume  of  CO^  Next, 
a  freshly  made  alkaline  solution  of  pyrogallic  acid  is  introduced  into  the  tube. 
This  solution  absorbs  all  of  the  oxygen,  whose  volume  is  thus  easily  determined. 
The  gas  that  is  left  unabsorbed  after  the  action  of  these  two  solutions  is  nitro- 
gen. The  volumes  of  gases  are  reduced,  as  is  the  custom,  to  unit  pressure 
and  temperature, — that  is,  to  zero  degree  centigrade  and  760  mms.  barometric 
pressure.  A  correction  must  also  be  made  for  the  tension  or  pressure  exerted 
by  the  aqueous  vapor  in  the  gases.  These  corrections  are  made  by  means 
of  the  following  formula: 


676 


PHYSIOLOGY    OF    RESPIRATION. 


V1  = 


— T) 


760  X  (1  +  0.003665 1) 

in  which  V1  represents  the  corrected  volume,  V  the  volume  actually  observed, 
B  the  barometric  height  at  the  time  and  place  of  the  observation,  T 
the  aqueous  tension  at  the  temperature  of  the  reading,  and  t  the  temperature 
in  degrees  centigrade. 

Determination  of  the  Oxygen  by  the  Potassium  Ferricyanide  Method. — For 
the  determination  of  the  oxygen  in  small  quantities  of  blood  a  convenient 

method  has  been  introduced  by  Haldane 
which  is  applicable  for  clinical  as  well  as 
experimental  purposes.  The  principle  of 
the  method  consists  in  first  laking  the  blood 
with  ammonia  and  then  adding  a  solution 
of  potassium  ferricyanide.  A  reaction  en- 
sues in  which  oxygen  is  given  off  in  an 
amount  identical  with  that  obtained  by 
submitting  the  blood  to  a  vacuum.  This 
method  has  found  a  convenient  appli- 
cation in  the  Barcroft  apparatus  (Fig. 
273),  in  which  the  volume  of  gas  liberated 
is  calculated  from  the  pressure  change 
caused  in  a  differential  manometer.  The 
manometer  (M)  is  a  U-tube,  provided  above 
with  stopcocks  through  which  communica- 
tion may  be  made  with  the  outside  air,  and 
connected  with  two  pear-shaped  bottles  in 
which  the  blood  to  be  analyzed  is  placed. 
The  manometer  contains  also  a  central  tube 
(A)  through  which  the  two  limbs  of  the 
manometer  may  be  filled  with  clove  oil  to 
a  certain  height  about  half  way  up  the 
tubes.  In  making  a  determination  the  stop- 
cocks are  left  open,  and  in  each  of  the  pear- 
shaped  bottles  one  places  1  c.c.  of  blood 
and  2  c.c.  of  dilute  ammonia.  The  appa- 
ratus is  thoroughly  shaken  to  lake  the 
blood,  and  then  on  one  side  a  little  of  a 
saturated  solution  of  potassium  ferricyanide 
is  placed  in  a  special  receptacle  in  the  stop- 
per of  one  of  the  pear-shaped  bottles.  The 
stoppers  are  inserted,  the  stopcocks  are 
closed,  and  then  by  turning  the  bottle  the 
ferricyanide  is  allowed  to  mix  with  the 
blood  on  its  side.  Oxygen  is  given  off,  and 
the  pressure  caused  by  it  is  indicated  by  the  difference  in  level  of  the  clove 
oil  in  the  two  limbs  of  the  manometer.  From  this  pressure  difference  the 
volume  of  the  gas  is  given  by  the  formula  x  =  k  p,  in  which  x  is  the  volume 
of  the  oxygen  gas  in  cubic  millimeters,  p  is  the  pressure  difference  shown  by 
the  manometer,  and  k  is  a  constant.  Before  using  the  apparatus  the  value 
of  k  must  be  determined  experimentally  by  liberating  a  known  volume  of 
oxygen  gas  and  determining  the  pressure  difference  produced.  For  this  pur- 
pose pure  H2O2  is  used,  and  the  oxygen  is  liberated  by  the  addition  of  a  solution 
of  potassium  permanganate.  In  this  case  x  and  p  are  known  and  k  may  be 

calculated,  k  =  — .  For  technical  details  consult  Barcroft,  "The  Respiratory 
Function  of  the  Blood,"  1914  (Appendix). 

By  means  of  such  methods  the  gases  in  the  blood  have  been  de- 
termined. The  quantities  vary  somewhat,  of  course,  with  the  con- 
dition of  the  animal  and  with  the  species  of  animal.  In  a  quick 
analysis  of  dogs'  arterial  blood  made  by  Pfliiger  the  following 


A 


Fig.  273. — Differential  manometer 
for  oxygen  determination  in  blood: 
M ,  The  manometer  containing  clove 
oil;  A,  the  central  tube  used  to  fill  M 
with  the  clove  oil.  The  manometer 
communicates  above  with  the  two 
pear-shaped  flasks  in  which  the  speci- 
mens of  blood  are  placed,  and  in  one 
of  which  the  oxygen  is  liberated  by  the 
action  of  the  potassium  ferricyanide. 
(See  text  for  description  of  the  method 
of  using.)  (Barcroft  and  Roberts.) 


CHANGES    IN    AIR    AND    BLOOD    IN    RESPIRATION.  677 

figures  were  obtained  reckoned  in  volumes  per  cent. :  O,  2.26;  C(>2, 
34.3;  N,  1.8.  In  this  case  each  100  c.c.  of  arterial  blood  contained 
22.6  c.c.  of  0  and  34.3  c.c.  of  CO2  measured  at  O°  C.  and  760  mms. 
Hg.  An  analysis  of  human  blood  (Setschenow)  gave  closely  similar 
figures;  0,  21.6  per  cent.;  C02J  40.3  per  cent.;  and  N,  1.6  per  cent. 
When  the  arterial  and  the  venous  bloods  are  compared  it  is  found 
that  the  venous  blood  has  more  carbon  dioxid  and  less  oxygen. 
Average  figures  showing  the  difference  in  composition  are  as  follows: 

O.  C03.  N. 

Arterial  blood 20  38  1.7 

Venous  blood 12  45  1.7 

Difference 870 

The  actual  amounts  of  oxygen  and  carbon  dioxid  in  the  venous 
blood  vary  with  the  nutritive  activity  of  the  tissues,  and  differ 
therefore  in  the  various  organs  according  to  the  state  of  activity  of 
each  organ  in  relation  to  the  volume  of  its  blood  supply.  This 
point  is  well  illustrated  by  some  analyses  made  by  Hill  and  Na- 
barro  *  of  the  gases  in  the  venous  blood  from  the  brain  and  the 
muscles,  respectively.  Their  average  results  when  both  tissues 
were  at  rest  were  as  follows: 

OXYGEN.  CARBON  DIOXID. 

Venous  blood  from  limbs  (femoral) ....  6.34  per  cent.         45.75  per  cent 
"     brain  (torcular)  . . .  13.49     "      "  41.65     "      " 

It  will  be  seen  that  under  similar  conditions  there  is  much  less 
oxygen  used  and  carbon  dioxid  formed  in  the  brain  than  in  the 
limbs  (muscles).  In  the  former  organ  the  physiological  oxidations 
must  either  be  small  compared  with  those  of  the  muscles,  or  the 
brain  tissues  receive  a  relatively  ample  supply  of  blood,  so  that  the 
tissue  metabolism  has  less  effect  upon  the  blood  composition.  The 
venous  blood  as  it  comes  to  the  lungs  is  a  mixture  of  bloods  from 
different  organs,  and  its  composition  in  gases  will  be  constant  only 
when  the  conditions  of  the  body  are  kept  uniform.  Much  work 
has  been  done  in  physiology  to  determine  the  condition  in  which 
these  various  gases  are  held  in  the  blood.  The  results  obtained 
show  that  they  are  held  in  small  part  in  solution,  but  mainly  in 
chemical  combination.  To  understand  the  part  played  by  each 
factor  and  the  conditions  that  control  the  exchange  of  gases  in 
the  lungs  and  tissues  it  is  necessary  to  recall  some  facts  regarding 
the  physical  and  chemical  properties  of  gases. 

The  Pressure  of  Gases  and  the  Terms  Expressing  these 
Pressures. — The  air  around  us  exists  under  a  pressure  of  one 
atmosphere  and  this  pressure  is  expressed  usually  in  terms  of  the 
height  of  a  column  of  mercury  that  it  will  support, — namely,  a 

*  Hill  and  Nabarro,  "Journal  of  Physiology,"  18,  218,  1895. 


678  PHYSIOLOGY    OF    RESPIRATION. 

column  of  760  mms.  Hg,  which  is  known  as  the  normal  barometric 
pressure  at  sea-level.  Air  is  a  mixture  of  gases,  and  according  to  the 
mechanical  theory  of  gas-pressure  each  constituent  exerts  a  pressure 
corresponding  to  the  proportion  of  that  gas  present.  In  atmospheric 
air,  therefore,  the  oxygen,  being  present  to  the  extent  of  20  per 
cent.,  exerts  a  pressure  of  ^  of  an  atmosphere  or  ^  X  760  =  152 
mms.  Hg.  When  we  speak  of  one  atmosphere  of  gas  pressure, 
therefore,  we  mean  a  pressure  equivalent  to  760  mms.  Hg,  and  in 
any  given  mixture  the  pressure  exerted  by  any  constituent  may 
be  expressed  in  percentages  or  fractions  of  an  atmosphere,  or  in  the 
equivalent  height  of  the  mercury  column  which  it  will  support. 

Absorption  of  Gases  in  Liquids. — When  a  gas  is  brought  into 
contact  with  a  liquid  with  which  it  does  not  react  chemically  a 
certain  number  of  the  moving  gaseous  molecules  penetrate  the 
liquid  and  become  dissolved.     Some  of  these  dissolved  molecules 
escape    from    the   water   from   time   to    time,    again   becoming 
gaseous.    It  is  evident,  however,  that  if  a  liquid,  water,  is  brought 
into  contact  with  a  gas  under  definite  pressure, — that  is,  containing 
a  definite  number  of  molecules  to  a  unit  volume, — an  equilibrium 
will  be  established.     As  many  molecules  will  penetrate  the  liquid 
in  a  given  time  as  escape  from  it,  and  the  liquid  will  hold  a  definite 
number  of  the  gas  molecules  in  solution;  it  will  be  saturated  for 
that  pressure  of  gas.     If  the  pressure  of  the  gas  is  increased,  how- 
ever, an  equilibrium  will  be  established  at  a  higher  level  and  more 
molecules  of  gas  will  be  dissolved  in  the  liquid.     Experiments  have 
shown,  in  accordance  with  this  mechanical   conception,  that  the 
amount  of  a  given  gas  dissolved  by  a  given  liquid  varies,  the  temper- 
ature remaining  the  same,  directly  with  the  pressure, — that  is,  it  in- 
creases and  decreases  proportionally  with  the  rise  and  fall  of  the 
gas  pressure.     This  is  the   law   of   Henry.     On  the  other  hand, 
the  amount  of  gas  dissolved  by  a  liquid  varies  inversely  with  the 
temperature.     It  follows,   also,   from  the  same  mechanical  views 
that  in  a  mixture  of  gases  each  gas  is  dissolved  in  proportion 
to  the  pressure  that  it  exerts,  and  not  in  proportion  to  the  pressure 
of  the  mixture.     Air  consists,  in  round  numbers,  of  4  parts  of  N  and 
1  part  of  0.     Consequently,  when  a  volume  of  water  is  exposed  to 
the  air  the  oxygen  is  dissolved  according  to  its  "  partial  pressure," 
—that  is,  under  a  pressure  of  ^  of  an  atmosphere  (152  mms.  Hg). 
The  water  will  contain  only  -J-  as  much  oxygen  as  it  would  if  exposed 
to  a  full  atmosphere  of  oxygen — that  is,  to  pure  oxygen.    And,  on 
the  other  hand,  if  water  has  been  saturated  with  oxygen  at  one 
atmosphere  (760  mms.)  of  pressure  and  is  then  exposed  to  air, 
four-fifths  of  the  dissolved  oxygen  will  be  given  off,  since  the  pressure 
of  the  surrounding  oxygen  has  been  diminished  that  much.     A  6- 


CHANGES    IN   AIR   AND    BLOOD    IN    RESPIRATION.  679 

sorption  coefficient.  By  this  term  is  meant  the  number  that  ex- 
presses the  proportion  of  gas  dissolved  in  a  unit  volume  of  the  liquid 
under  one  atmosphere  of  pressure.  The  absorption  coefficient  will 
vary,  of  course,  with  the  temperature.  The  gases  that  interest  us 
in  this  connection  are  oxygen,  nitrogen,  and  carbon  dioxid.  The 
absorption  coefficients  of  these  gases  for  the  blood  at  the  tempera- 
ture of  the  body  are  as  follows:  O,  0.0262;  N,  0.0130;  CO2,  0.5283.* 
That  is,  1  c.c.  of  blood  at  body  temperature  dissolves  0.0262  of 
1  c.c.  of  oxygen  if  exposed  to  an  atmosphere  of  pure  oxygen,  and 
so  on.  The  solubility  of  the  COf  is  therefore  twenty  times  as  great 
as  that  of  oxygen.  Accepting  these  figures,  we  may  calculate  how 
much  of  these  three  gases  can  be  held  in  the  arterial  blood  in  physical 
solution,  provided  we  know  the  pressure  of  the  gases  in  the  alveoli 
of  the  lungs.  The  composition  of  the  alveolar  air  will  be  discussed 
farther  on,  but  we  may  assume  at  present  that  it  contains  80  per 
cent,  of  nitrogen,  15  per  cent,  of  oxygen,  and  5  per  cent,  of  carbon 
dioxid.  In  100  c.c.  of  blood,  therefore,  the  following  amounts  of 
these  gases  should  be  held  in  solution: 

Nitrogen 100X0.013    X  0.80  =  1.04    c.c. 

Oxygen 100  X  0.0262  X  0.15  =  0.393    " 

Carbon  dioxid 100  X  0.5283  X  0.05  =  2.64     " 

As  will  be  seen  from  the  analyses  given  above  of  the  actual  amounts 
of  these  gases  obtained  from  the  blood,  the  nitrogen  alone  is  present 
in  quantities  corresponding  to  what  would  be  expected  if  it  is 
held  in  simple  physical  solution. 

The  Tension  or  Pressure  of  Gases  in  Solution  or  Combi- 
nation.— When  a  gas  is  held  in  solution  the  equilibrium  is  de- 
stroyed if  the  pressure  of  this  gas  in  the  surrounding  medium  or 
atmosphere  is  changed.  If  this  pressure  is  increased  the  liquid 
takes  up  more  of  the  gas,  and  an  equilibrium  is  established  at  a 
higher  level.  If  the  pressure  is  decreased  the  liquid  gives  off 
some  of  the  gas.  The  pressure  of  the  gas  in  the  surrounding  at- 
mosphere at  which  equilibrium  is  established  measures  the  tension 
of  the  gas  in  the  liquid  at  that  time.  Thus,  when  a  bowl  of  water  is 
exposed  to  the  air  the  tension  of  the  oxygen  in  solution  is  152  mms. 
Hg;  that  of  the  nitrogen  is  608  mms.  Hg.  If  the  same  water  is 
exposed  to  pure  oxygen  the  tension  of  the  oxygen  in  solution  is 
equal  to  760  mms.  Hg,  while  that  of  the  nitrogen  sinks  to  zero  if 
the  gas  that  is  given  off  from  the  water  is  removed.  With  com- 
pounds such  as  oxyhemoglobin  the  tension  under  which  the  oxy- 

*As  given  by  Bohr,  the  absorption  coefficients  of  these  three  gases 
at  40°  C.  are  as  follows:  Oxygen,  00231;  nitrogen,  0.0118;  carbon  dioxid, 
0.530. 


680 


PHYSIOLOGY    OF    RESPIRATION. 


gen  is  held  is  measured  by  the  pressure  of  the  gas  in  the  sur- 
rounding atmosphere  at  which  the 
compound   neither  takes   up   nor 
gives  off  oxygen.    If,  therefore,  it 
is  necessary  to  determine  the  ten- 
sion of  any  gas  held  in  solution 
or  in  dissociable  combination  it  is 
sufficient  to   determine    the    per- 
centage of  that  gas  in  the  sur- 
rounding   atmosphere    and    thus 
ascertain  the  partial  pressure  that 
it  exerts.    If  the  atmosphere  con- 
tains 5  per  cent,  of  a  given  gas 
the  partial  pressure  exerted  by  it, 
leaving  out  of  account  the  aqueous 
tension,  is  equal  to  38  mms.  Hg. 
(760  X  0.05) ,  and  this  figure  express- 
es the  tension  under  which  the  gas 
is  held  in  solution  or  combination  in 
a  liquid  exposed  to  such  an  atmos- 
phere.   As  regards  the  tension  of 
the  gases  in  arterial  and  venous 
blood,  this  procedure  is,  of  course, 
not    possible,   since  the  blood  is 
surrounded,  not  by  an  atmosphere 
whose  composition  can  be  anal- 
yzed, but  by  the  liquids  of  the 
body,  the  lymph  and  cell  juices. 
To  determine  the  tension  of  the 
gases  in  the  blood  it  is  necessary 
to    remove   the    blood   from    the 
vessels  and  bring  it  into  contact 
with  an  atmosphere  containing  a 
known  quantity  of  O,  CO2,  or  N, 
according  to  the  gas  to  be  measured.     By  trial  an  atmosphere  can 
be  obtained  in  which  this  gas  is  contained  in  amounts  such  that  there 
is  no  marked  increase  or  decrease  in  quantity  after  standing  in  diffu- 
sion relations  with  the  blood.   The  percentage  of  the  gas  in  the  at- 
mosphere chosen  will  measure  the  tension  of  that  gas  in  the  blood. 
An  instrument  which  has  been  much  used  for  such  determinations  is 
represented  diagrammatically  in  Fig.  274.    It  is  known  as  a  tonom- 
eter or  aerotonometer  (Pfliiger).     It  consists  of  a  tube  (A)  which 
can  be  connected  through  6  directly  with  the  blood-vessels.     This 
tube  A  is  surrounded  by  a  jacket  (C)  containing  warm  water,  so 


274. — Diagram  to  show  the 
principle  of  the  aerotonometer:  A,  The 
tube  containing  a  known  mixture  of 
gases,  O,  CO?,  N;  C,  the  outside  jacket 
for  maintaining  a  constant  body  tem- 
perature. When  stopcock  6  is  open 
the  blood  trickles  down  the  sides  of  A 
and  enters  into  diffusion  relations  with 
the  contained  gases.  After  equilibrium 
is  reached  the  stopc'ock  t;  is  closed  and 
a  is  opened.  By  means  of  the  mer- 
cury bulb  the  gases  can  then  be  forced 
out  of  A  into  a  suitable  receiver  for 
analysis. 


CHANGES    IN    AIR    AND    BLOOD    IN    RESPIRATION.  681 

that  the  blood  may  be  kept  at  the  body  temperature  during  the  ex- 
periment. A  is  first  completely  filled  with  mercury  from  the  bulb  M 
to  drive  out  the  air.  An  atmosphere  of  known  composition  is 
then  sucked  into  A  by  dropping  the  bulb.  Blood  is  allowed  to 
flow  into  A  through  the  stopcock  6  and  to  trickle  down  the  sides 
of  the  tube.  Diffusion  relations  are  set  up  between  the  blood 
and  the  known  atmosphere,  and  after  equilibrium  has  been  estab- 
lished the  gas  is  driven  out  through  a  into  a  convenient  receiver 
and  analyzed.  If  two  aerotonometers  are  used,  one  containing 
the  gas  at  somewhat  higher  pressure  than  that  expected,  and  the 
other  at  a  somewhat  lower  pressure,  an  average  result  is  obtained 
which  expresses  with  sufficient  accuracy  the  pressure  of  the  given 
gas  in  the  blood.* 

It  is  important  not  to  confuse  the  tension  at  which  a  gas  is  held 
in  a  liquid  with  the  volume  of  the  gas  in  solution.  Thus,  blood 
exposed  to  the  air  contains  its  oxygen  under  a  tension  of  152  mms. 
Hg,  but  the  amount  of  oxygen  is  equal  to  20  volumes  per  cent. 
Water  exposed  to  the  air  contains  its  oxygen  under  the  same 
tension,  but  the  amount  of  gas  in  solution  is  less  than  1  volume 
per  cent.  Tensions  of  gases  in  liquids  are  expressed  either  in  per- 
centages of  an  atmosphere  or  in  millimeters  of  mercury.  Thus,  the 
tension  of  oxygen  in  arterial  blood  is  found  to  be  equal  to  about 
13  per  cent,  of  an  atmosphere  or  100  mms.  Hg.  (760  X  0.13). 

The  Condition  and  Significance  of  the  Nitrogen. — We  may 
accept  the  view  that  the  nitrogen  of  the  blood  is  held  in  physical 
solution.  The  amount  present  corresponds  with  this  view,  and, 
moreover,  it  is  found  that  the  quantity  varies  directly  with  the 
pressure  in  accordance  with  the  law  given  above.  If  an  animal 
is  permitted  to  breathe  an  atmosphere  of  oxygen  and  hydrogen 
the  nitrogen  disappears  from  the  blood,  and  when  ordinary  air  is 
breathed  the  nitrogen  contents  of  the  arterial  and  venous  bloods 
exhibit  no  constant  difference  in  quantity.  It  seems  certain,  there- 
fore, that  the  nitrogen  plays  no  direct  role  in  the  physiological  pro- 
cesses. It  is  absorbed  by  the  blood  in  proportion  to  its  partial 
pressure  in  the  alveoli  of  the  lungs  and  circulates  in  the  blood  in 
small  amounts  without  exerting  any  immediate  influence  upon  the 
tissues. 

Condition  of  Oxygen  in  the  Blood. — That  the  oxygen  is  not 
held  in  the  blood  merely  in  solution  is  indicated,  in  the  first  place, 
by  the  large  quantity  present  and,  in  the  second  place,  by  the  fact 
that  this  quantity  does  not  vary  directly  with  the  pressure  in  the 
surrounding  medium.  It  is  definitely  known  that  by  far  the  largest 

*  For  description  of  more  modern  instruments,  see  Tigerstedt,  "Handbuch 
d.  physiologischen  Methodik,"  vol.  ii.,  1911. 


682  PHYSIOLOGY    OF    RESPIRATION. 

portion  of  the  oxygen  is  held  in  chemical  combination  with  the 
hemoglobin  of  the  red  corpuscles,  while  a  much  smaller  portion, 
varying  with  the  pressure,  is  held  in  solution  in  the  plasma.  The 
compound  oxyhemoglobin  possesses  the  important  property  that 
when  the  pressure  of  oxygen  in  the  surrounding  medium  falls  suffi- 
ciently it  begins  to  dissociate  and  free  oxygen  is  given  off.  The  proc- 
ess of  dissociation  is  facilitated  also  by  increase  of  temperature, 
provided,  of  course,  that  it  does  not  rise  to  the  point  of  coagulating 
the  hemoglobin.  The  amount  of  dissociation  that  takes  place  under 
different  pressures  of  oxygen  in  the  surrounding  medium  has  been 
studied  both  for  solutions  of  pure  hemoglobin  *  and  for  defibrinated 
blood,  f  It  would  seem  from  this  work  that  the  compound 
between  oxygen  and  hemoglobin  is  more  easily  dissociated  when  the 
hemoglobin  is  in  its  natural  condition  in  the  corpuscles  than  when  it 
has  been  crystallized  out  and  obtained  in  pure  solutions.  The  re- 
sults that  have  been  obtained  from  experiments  upon  defibrinated 
blood  probably  represent,  therefore,  more  nearly  the  conditions 
of  dissociation  in  the  body.  The  results  obtained  by  Bohr  are 
indicated  in  the  curve  of  dissociation  shown  in  Fig.  275,  obtained 
from  experiments  on  dog's  blood.  At  a  pressure  of  oxygen  of 
152  mms. — that  is,  when  exposed  to  ordinary  air — the  hemoglobin 
is  nearly  or  completely  saturated  with  oxygen.  If  the  oxygen 
pressure  is  increased, — if,  for  instance,  the  blood  is  exposed  to  pure 
oxygen  (pressure,  760  mms.), — no  more  oxygen  is  combined 
chemically  by  the  hemoglobin.  Additional  oxygen  will  be  taken 
up  by  the  blood,  but  only  in  so  far  as  it  can  pass  into  solution  in  the 
blood-plasma.  Oxygen  thus  dissolved  in  the  blood-plasma  obeys 
the  physical  law  of  solution,  and  will  be  at  once  given  off  when  the 
oxygen  pressure  of  the  surrounding  medium  is  lowered.  If  the 
pressure  of  oxygen  falls  below  that  of  the  air  (152  mms.)  the  chemi- 
cally combined  oxyhemoglobin  begins  to  dissociate  slowly  at  first, 
but  as  the  pressure  falls  below  70  mms,  the  dissociation  becomes 
much  more  rapid,  and  the  oxygen  thus  liberated  from  chemical 
combination  is  from  a  quantitative  standpoint  much  more  impor- 
tant than  that  freed  from  solution  in  the  plasma.  This,  in  fact, 
is  the  process  that  takes  place  as  the  blood  circulates  through  the 
tissues.  The  arterial  blood  enters  the  capillaries  with  its  hemo- 
globin nearly  saturated  with  oxygen, — about  19  c.c.  to  each  100  c.c. 
of  blood.  After  it  leaves  the  capillaries  the  venous  blood  contains 
only  about  12  volumes  of  oxygen  to  each  100  c.c.  of  blood.  In  the 
passage  of  the  capillaries,  which  takes  only  about  one  second,  the 
blood  loses,  therefore,  about  35  per  cent,  or  more  of  its  oxygen. 

*Hufner,  "Archiv  f.  Physiologie,"  suppl.  volume,  1901,  p.  213. 
t  Loewy,  "Archiv  f.  Physiologie,"  1904,  p.  235. 


CHANGES    IN    BLOOD    AND    AIR    IN    RESPIRATION. 


683 


The  physical  theory  of  respiration  furnishes  data  to  show  that  this 
loss  is  due  to  a  dissociation  of  the  oxyhemoglobin,  owing  to  the  fact 
that  in  passing  through  the  capillaries  the  blood  is  brought  into 
exchange  with  a  surrounding  medium — lymph,  cell  liquid — in 
which  the  oxygen  pressure  is  very  low.  An  additional  fact  of  im- 
portance in  this  connection  is  shown  by  the  curves  produced 
in  Fig.  275.  In  the  tissues  where  the  oxyhemoglobin  undergoes 
dissociation  with  the  liberation  of  oxygen,  and  in  the  lungs  where 
the  hemoglobin  takes  up  oxygen  from  the  alveolar  air,  the  blood 


100 
90 
80 

70 

60 


/ 


// 


^ 


10    10     30     40    50     60    70    80    90    100  110    1£0   130  140 


160 


Fig.  275. — Curves  of  dissociation  of  the  oxyhemoglobin  at  different  pressures  of 
oxygen.  Five  curves  are  shown  to  indicate  that  the  dissociation  of  the  oxyhemoglobin 
is  greatly  influenced  by  the  presence  of  CO2.  The  figures  along  the  orqUnates  (10  to  100) 
indicate  percentages  of  saturation  of  the  hemoglobin  with  oxygen,  while  the  figures  along 
the  abscissa  (0  to  160)  indicate  different  pressures  of  oxygen.  The  curve  marked  5  mm. 
CO2  shows  the  amount  of  combination  of  oxygen  and  hemoglobin  when  the  CO2  is  absent 
or  present  only  in  traces.  In  this  curve  at  a  pressure  of  30  mms.  of  oxygen  it  will  be  seen 
that  the  hemoglobin  is  80  per  cent,  saturated  with  oxygen,  while  with  a  pressure  of  40  mms. 
of  CO2,  which  approximates  that  in  the  body,  the  hemoglobin  at  the  same  pressure  of 
oxygen  is  only  50  per  cent,  saturated.  (After  Bohr.) 

is  surrounded  by  a  medium  containing  both  oxygen  and  carbon 
dioxid.  Laboratory  experiments  show  that  the  presence  of  the 
carbon  dioxid  influences  the  dissociation  curve  in  the  direction 
indicated  in  the  figure.  At  a  carbon  dioxid  pressure  equivalent  to 
that  of  the  alveolar  air  (40  mms.)  it  will  be  noticed  that  the  curve 
is  lower,  that  is,  at  any  given  pressure  of  oxygen,  30  mms.,  for 
example,  less  oxygen  will  be  held  by  the  hemoglobin,  or  the  per- 
centage saturation  of  the  hemoglobin  with  oxygen  will  be  lower. 
So  also  changes  in  the  reaction  of  the  blood  toward  the  acid  side, 
the  condition  designated  in  medicine  as  acidosis,  will  be  accom- 
panied by  a  similar  lowering  of  the  curve  of  dissociation,  that  is, 
by  a  diminished  capacity  of  the  hemoglobin  for  oxygen  at  these 
pressures  below  the  saturation  point.  In  determining  the  actual 


684 


PHYSIOLOGY    OF    RESPIRATION. 


dissociation  curve  of  the  blood  in  man  it  is  desirable,  therefore, 
to  obtain  the  figures  expressing  the  percentage  saturation  of  the 
hemoglobin  in  atmospheres  containing  carbon  dioxid  in  amounts 
equal  to  that  found  in  the  alveolar  air  of  the  individual  examined. 
In  Fig.  275  a  a  dissociation  curve  for  human  blood  is  given  in 
which  this  factor  was  considered.  The  curve  shows  also,  in  the 
thickness  of  the  line,  the  individual  variations  that  may  be  ex- 
pected in  the  bloods  of  normal  persons.  For  example,  at  an 
oxygen  pressure  of  40  mms.  the  percentage  saturation  of  the  hemo- 
globin for  oxygen  varies  between  70  and  78  or  79.  For  a  blood 


10         20         30 


60         60         70         80         90        100 


Fig.  275  a. — The  dissociation  curve  for  human  blood.  The  thickness  of  the  curve  indicates 
the  limits  within  which  the  curve  may  fall  for  normal  persons.  The  figures  along  the  abscissa 
indicate  the  pressure  of  oxygen  in  mms.  of  mercury;  those  along  the  ordinate  indicate  the  per- 
centage saturation  of  the  hemoglobin  with  oxygen.  (From  Barcroft,  "The  Respiratory  Func- 
tion of  the  Blood."  By  permission  of  University  Press,  Cambridge,  England,  Publishers.) 

that  falls  within  the  limits  indicated  by  the  curve  Barcroft*  pro- 
poses the  designation  mesectic.  Bloods  which  at  any  given  pres- 
sure, below  saturation,  take  up  a  larger  percentage  of  oxygen 
(higher  curve)  may  be  called  pleonedic,  while  those  which  under 
the  same  conditions  are  less  saturated  than  normal  (lower  curve) 
are  mdonectic. 

Condition  of  the  Carbon  Dioxid  in  the  Blood. — The  condition 
in  which  the  carbon  dioxid  is  held  in  the  blood  is  not  entirely 
understood.  It  has  long  been  recognized  that  a  certain  small 
percentage  is  held  in  simple  physical  solution  in  the  plasma  and 
in  the  corpuscles,  and  that  a  certain  additional  amount,  much 

*  Barcroft,  "The  Respiratory  Function  of  the  Blood,"  1914. 


CHANGES    IN    AIR   AND    BLOOD    IN    RESPIRATION.  685 

larger  than  the  preceding,  is  chemically  combined  with  the 
alkali  of  the  blood  as  a  carbonate,  most  probably  as  a  bicarbonate 
(HNaC03).  Other  facts  tend  to  show  that  the  available  alkali 
of  the  blood  in  combination  as  carbonate  or  phosphate  is  not 
sufficient  to  combine  with  the  quantity  of  carbon  'dioxid  normally 
present.  In  recent  years  an  additional  possibility  has  been  sug- 
gested by  the  discovery  (Bohr)  that  carbon  dioxid  forms  a  disso- 
ciable compound  with  hemoglobin  (p.  430),  and  the  probability 
that  a  similar  compound  may  be  formed  with  the  proteins  of  the 
plasma.  Accepting  this  suggestion  it  would  seem  that  the  carbon 
dioxid  exists  in  the  blood  in  three  forms.  The  amounts  present 
in  each  form  is  estimated  by  Loewy*  as  follows:  In  each  100  c.c. 
of  arterial  blood,  containing  normally  40  volume  per  cent,  of 
carbon  dioxid,  there  is 

Physically  absorbed  in  plasma  and  corpuscles 1.9  per  cent. 

Held  as  sodium  bicarbonate  {  £  ^"f68; ; ;  £*  }  . .  18.8    "       " 

Held  in  organic  combination  {  £  JgJ*^  ; ;  Jj }  . .  19.3    "       « 

When  serum  or  plasma  is  exposed  to  a  vacuum  at  body  tem- 
perature only  a  portion  of  the  carbon  dioxid  is  given  off;  to 
obtain  the  balance  it  is  necessary  to  add  acid  to  the  liquid.  This 
latter  portion,  liberated  only  by  a  stronger  acid,  is  spoken  of  as 
the  " fixed  carbon  dioxid."  If  instead  of  exposing  serum  or 
plasma  to  a  vacuum  one  uses  full  blood,  that  is,  plasma  or  serum 
plus  corpuscles,  all  the  carbon  dioxid  may  be  obtained  without 
the  necessity  of  adding  acid.  This  fact  has  been  explained  on 
the  supposition  that  the  hemoglobin  under  these  conditions 
plays  the  part  of  an  acid  in  breaking  up  the  compound  in  which 
the  carbon  dioxid  is  firmly  held,  although  experiments  showf 
that  it  has  no  such  effect  upon  aqueous  solutions  of  sodium  bicar- 
bonate. Since  the  portion  that  is  held  in  organic  combination  is 
apparently  more  easily  dissociated,  it  seems  likely  that  it  furnishes 
the  main  compound  which  is  physiologically  useful  in  providing  a 
means  for  the  transportation  of  carbon  dioxid  from  the  tissues, 
where  it  is  formed,  to  the  lungs,  where  it  is  eliminated. 

The  Physical  Theory  of  Respiration. — The  physical  theory 
of  respiration  assumes  that  the  gaseous  exchange  in  the  lungs  and 
in  the  tissues  takes  place  in  accordance  with  the  physical  laws  of 
diffusion  of  gases.  If  a  permeable  membrane  separates  two  vol- 
umes of  any  gas,  or  two  solutions  of  any  gas  at  different  pressures, 
the  molecules  of  the  gas  will  pass  through  the  membrane  in  both 

*  Loewy,  "Handbuch  d.  Biochemie,"  1908,  IV. 

f  Buckmaster,  "Journal  of  Physiology,"  51,  105,  1917. 


686  PHYSIOLOGY    OF    RESPIRATION. 

directions  until  the  pressure  is  equal  on  both  sides.  As  the  excess 
of  movement  is  from  the  point  of  higher  pressure  to  the  point  of 
lower  pressure,  attention  is  paid  only  to  this  side  of  the  process, 
and  we  say  that  the  gas  diffuses  from  a  point  of  high  tension  to 
one  of  lower  tension.  After  equilibrium  is  established  and  the 
pressure  is  the  same  on  both  sides  we  must  imagine  that  the 
diffusion  is  equal  in  both  directions,  and  the  condition  is  the  same 
as  though  there  were  no  further  diffusion.  In  order  for  this 
theory  to  hold  for  the  exchange  in  the  body  it  must  be  shown  that 
the  physical  conditions  are  such  as  it  demands.  Numerous  experi- 
ments have  been  made,  therefore,  to  determine  the  actual  pressure 
of  the  oxygen  and  carbon  dioxid  in  the  venous  blood  as  com- 
pared with  the  pressures  of  the  same  gases  in  the  alveolar  air,  and 
the  pressures  in  the  arterial  blood  as  compared  with  those  in  the 
tissues.  Although  the  actual  figures  obtained  have  varied  some- 
what with  the  method  used,  the  species  or  condition  of  the  ani- 
mal, yet,  on  the  whole,  the  results  tend  to  support  the  physical 
theory. 

The  Gaseous  Exchange  in  the  Lungs.— It  is  difficult  to  deter- 
mine the  exact  composition  of  the  alveolar  air.  The  expired 
air  can,  of  course,  be  collected  and  analyzed,  but  obviously  this  is  a 
mixture  of  the  air  in  the  bronchi  and  the  alveoli,  and  consequently 
has  more  oxygen  and  less  carbon  dioxid  than  the  air  in  the  alveoli. 
The  probable  composition  of  the  alveolar  air  has  been  calculated  by 
Zuntz  and  Loewy  for  normal  quiet  breathing  in  the  following  way : 
The  capacity  of  the  bronchial  tree  is  140  c.c.,  and  this  air  may  be 
considered  as  similar  in  composition  to  atmospheric  air,  that  is,  the 
inspired  air.  A  normal  expiration  contains  500  c.c.;  hence  the 
alveolar  air  constitutes  only  360  c.c.  or  if  of  the  entire  amount.  If 
the  expired  air  contains  4.38  per  cent,  of  CO2,  then  the  alveolar 
air  must  contain  4.38  +  if,  or  6  per  cent,  of  carbon  dioxid.* 

Or,  to  put  the  mode  of  calculation  in  a  more  general  form,  the  amount 
of  oxygen  in  the  expired  air  is  equal  to  the  amount  of  oxygen  in  the  true 
alveolar  portion  of  the  expired  air  plus  the  amount  of  oxygen  in  the  "dead 
space, "  namely,  the  trachea  and  bronchi.  Let  A  equal  the  volume  of  expired 
air,  e  the  percentage  of  oxygen  in  the  expired  air,  a  the  volume  of  air  in  the 
dead  space,  and  i  the  percentage  of  oxygen  in  this  air  or  what  is  the  same 
thing  in  the  inspired  air.  According  to  the  above  statement  we  have  the  fol- 
lowing equation,  A.e  •=  ai  -+-  (A  —  a)  ,x,  in  which  x  represents  the  unknown 
percentage  of  oxygen  in  the  alveolar  air.  We  have,  therefore,  x  =  A£~™- 
In  ordinary  breathing  these  values  are  as  follows:  A  =^=  500  c.c.,  a  ==  140  c.c., 
e  =  16.02  per  cent.,  and  i  =  20.96  per  cent.  Substituting  these  values,  x  will  be 
found  equal  to  14.1  per  cent.  Reckoned  in  millimeters  of  mercury  this  would 
be  equal  to  (760  X  0.141)  107.2  mm.  In  order,  however,  to  ascertain  the 
true  pressure  exerted  by  the  oxygen  allowance  must  be  made  for  the  baro- 
metric pressure  and  for  the  tension  of  the  aqueous  vapor.  In  the  depths  of 
the  Jungs  the  air  is  saturated  with  water  vapor  and  the  tension  of  this  vapor 
at  the  body  temperature  may  be  valued  at  46.6  mms.  Hg.  If  we  suppose 

*  For  discussion  of  methods,  see  Krogh  and  Lindhard,  "Journal  of  Phys- 
iology," 47,  431,  1914. 


CHANGES    IN    AIR   AND    BLOOD    IN    RESPIRATION.  687 

further  that  the  observation  was  made  at  a  barometric  pressure  of  760  mms., 
then  the  pressure  of  the  oxygen  in  the  alveoli  would  be  (760—46.6X0.147) 
99+  mms.  Hg. 

Actual  observations  made  by  these  authors  upon  human  beings 
in  whom  the  expired  air  was  analyzed  indicate  that  the  composition 
of  the  alveolar  air  may  vary  under  different  conditions  between 
the  following  limits:  Oxygen  between  11  and  17  per  cent,  of  an 
atmosphere;  carbon  dioxid  between  3.7  and  5.5  per  cent,  of  an 
atmosphere.  Haldane  and  Priestley  have  devised  a  simple 
method  by  means  of  which  the  last  portions  of  the  air  breathed 
out  in  an  expiration  may  be  collected.  The  sample  thus  collected 
represents  practically  the  alveolar  air,  and  its  average  composition 
for  normal  quiet  respirations  may  be  given  as  oxygen,  14  per  cent,  or 
100  mms.  Hg.  (760—46.6X0.14);  carbon  dioxid,  5.5  per  cent,  or 
40  mms.  Hg.;  nitrogen,  80  per  cent,  or  570  mms.  Hg.  Other  ob- 
servers state  that  the  direct  determination  of  the  CO2  in  the  alveolar 
air  by  the  method  of  Haldane  and  Priestley  gives  figures  that  are 
too  high,  and  that  it  is  safer  to  estimate  this  factor  indirectly. 
Pearce*  suggests  the  following  method:  The  expired  air  from  two 
expirations  of  different  depths  is  collected,  measured  exactly,  and 
analyzed  for  its  CO2.  With  these  factors  known,  and  representing 
the  percentage  of  CO2  in  the  alveolar  air  by  y,  and  the  volume  of 
the  dead  space  by  x,  a  binominal  equation  may  be  expressed  which 
can  be  solved  for  either  x  or  y.  Thus, 

A  =  amount  of  air  in  large  expiration. 

A\  =  amount  of  air  in  small  expiration. 

B  =  percentage  of  CO2  in  the  large  expiration. 

BI  =  percentage  of  CO2  in  the  small  expiration. 

Then  AB  =  (A—x)y, 

A!  Bi  =  (Al—x}y. 
Solving  this  equation  for  y,  we  find — 
_  AB—Ai  Bi 
A— At 

The  author  reports  an  average  value  for  y  of  5.45  per  cent. 

Loewy  and  von  Schrotter  have  determined  also  the  average 
tension  of  these  gases  in  the  blood  of  man.  Their  method*  con- 
sisted in  blocking  off  one  lung  or  one  lobe  of  a  lung  by  a  metal 
catheter  inserted  through  the  trachea.  After  the  lapse  of  half  an 
hour  or  so  the  gases  in  this  occluded  portion  had  reached  an 
equilibrium  by  interchange  with  the  venous  blood  which  repre- 
sented the  tension  actually  existing  in  the  circulating  venous 
blood.  A  portion  of  this  air  was  then  withdrawn  by  means  of  a 
suitable  device  and  was  analyzed.  Their  average  result  was  that 

*  Pearce,  "American  Journal  of  Physiology,"  43,  73,  1917. 

t  Loewy  and  von  Schrotter,  "Zeitschrift  fur  experimentelle  Pathologic 
und  Therapie,"  1,  197,  1905.  See  also  Loewy,  "Handbuch  der  Biochemie," 
IV  ,  1908. 


688  PHYSIOLOGY    OF    RESPIRATION. 

in  the  venous  blood  the  oxygen  exists  under  a  tension  of  5.3  per 
cent,  of  the  alveolar  atmosphere  (710  X  .053  =  37.6  mms.  Hg.), 
and  the  CO2  under  a  tension  of  6  per  cent.  (42.6  mms.  Hg.).  The 
physical  relations  of  pressure  between  the  alveolar  air  and  the 
gases  in  the  venous  blood  may  be  represented  as  follows  : 

OXYGEN.  CARBON  Dioxin. 

Alveolar  air  ........   100  mms.  35  to  40  mms. 

Membrane  ......  -  1  -        -  +  - 

f  I 

Venous  blood  .  .  .         37.6  mms.  42.6  mms. 

Diffusion  must  take  place,  therefore,  in  the  direction  indicated 
by  the  arrows.  As  the  oxygen  passes  through  into  the  blood  it  is 
combined  with  the  hemoglobin  and  it  is  estimated  that  the  arterial 
blood  as  it  flows  away  from  the  lungs  is  nearly  saturated  with 
oxygen,  lacking  perhaps  only  1  volume  per  cent,  of  being  completely 
saturated  (Pfliiger).  That  is,  if  the  normal  arterial  blood  contains 
19  c.c.  of  oxygen  for  each  100  c.c.  of  blood,  it  is  probable  that  one 
more  cubic  centimeter  might  be  combined  by  the  hemoglobin  if 
exposed  fully  to  the  air  or  oxygen.  The  difference  in  tension 
between  the  carbon  dioxid  on  the  two  sides  of  the  membrane  is  not 
so  great  as  in  the  case  of  the  oxygen,  but  owing  to  the  more  rapid 
diffusion  of  this  gas  it  is  probable  that  this  difference  suffices  to 
explain  the  exchange.  In  this  matter  one  must  bear  in  mind  also 
the  very  large  expanse  of  surface  offered  by  the  lungs  and  the  very 
complete  subdivision  of  the  mass  of  blood  in  the  capillaries.  Thus, 
following  a  calculation  made  by  Zuntz,  the  surface  of  the  human 
lungs  may  be  estimated  at  90  sq.ms.  or  900,000  sq.cms.  If  we 
assume  that  300  c.c.  of  carbon  dioxid  (500  X  0.04  X  15)  are  given 
off  from  the  blood  in  a  minute  this  would  indicate  a  diffusion 
through  each  square  centimeter  of  only  0.0003  c.c. 


This  same  idea  is  expanded  by  Loewy  as  follows:  The  surface  of  the 
lungs  exposed  to  the  air  may  be  reckoned  at  90  square  meters,  and  the  thick- 
ness of  membrane  intervening  between  this  air  and  the  blood  in  the  capillaries 
may  be  estimated  at  0.004  of  a  millimeter.  Under  these  conditions  as  much 
as  6083  c.c.  of  oxygen  might  diffuse  into  the  blood  in  a  minute.  As  a  matter 
of  fact  only  about  250  to  300  c.c.  of  oxygen  are  really  absorbed  per  minute  in 
quiet  breathing,  and  not  more  than  ten  times  this  amount  in  the  violent 
respiration  following  excessive  muscular  exercise.  It  would  seem,  therefore, 
that  diffusion  should  suffice  to  supply  the  oxygen  actually  needed.  This 
reasoning  applies  a  fortiori  to  the  carbon  dioxid,  since  the  velocity  of  diffusion 
of  this  gas  through  a  moist  membrane  is  much  (25  times)  greater.  If  the 
tension  of  the  CO2  in  the  blood  were  only  0.03  mm.  higher  than  that  in  the 
alveoli,  the  known  exchange  might  be  explained  by  diffusion. 

Exchange  of  Gases  in  the  Tissues.  —  The  arterial  blood  passes 
to  the  tissues  nearly  saturated  with  oxygen  so  far  as  the  hemo- 
globin is  concerned,  and  this  oxygen  is  held  under  a  tension 
equivalent  probably  to  at  least  100  mms.  Hg.  The  carbon 
dioxid  is  less  in  quantity  than  on  entering  the  lungs  and  exists 
under  a  smaller  pressure,  which  may  be  assumed  to  be  the  same 


CHANGES    IN    AIR    AND    BLOOD    IN    RESPIRATION.  689 

as  that  of  the  carbon  dioxid  in  the  alveoli  of  the  lungs — namely, 
5.5  per  cent,  of  the  alveolar  atmosphere  (40  mms.).  In  the  sys- 
temic capillaries  the  blood  comes  into  diffusion  relations  with  the 
tissues,  and  direct  examination  of  the  latter  shows  that  the  oxygen 
in  them  exists  under  a  very  small  pressure,  practically  zero  pres- 
sure,* while  the  CO2  is  present  under  a  tension  (Strassburg)  of 
7  to  9  per  cent.  The  high  tension  of  the  C02  is  explained  by 
the  fact  that  it  is  being  formed  in  the  tissues  constantly  as  a 
result  of  their  metabolism,  while  the  low  tension  of  the  oxygen 
is  due  to  the  fact  that  on  entering  the  tissue  this  substance  is 
combined  in  some  way  in  a  chemical  compound  too  firm  to 
dissociate.  The  physical  conditions  are,  therefore,  such  as 
would  cause  a  stream  of  CO2  from  tissue  to  blood  and  a  stream 
of  oxygen  in  the  reverse  direction. 

1  OXYGEN.          CARBON  DIOXID. 
Arterial  blood 100  mms.  35  mms. 

I  4- 


Wall  of  capillary 

Tissues 0  mm.  50  to  70  mms. 

It  is  to  be  remembered  that  in  this  exchange  the  blood  and 
the  lymph  act  as  intermediaries.  The  CO2  diffuses  from  lymph 
to  plasma  and  from  tissues  to  lymph.  The  oxygen  diffuses  from 
lymph  to  tissues,  from  plasma  to  lymph,  and  from  oxyhemo- 
globin  to  plasma.  Bohr*  has  found  experimentally  that  in 
blood,  when  the  oxygen  tension  is  low,  an  increase  in  the  CO2 
pressure  tends  to  dissociate  the  oxy hemoglobin  (Fig.  275). 
Since  these  conditions  prevail  in  the  capillaries  of  the  body,  it 
is  probable  that  the  presence  of  the  C02  in  increased  amounts 
facilitates  the  liberation  of  the  oxygen. 

Suggested  Secretory  Activity  in  the  Respiratory  Exchange. — The  view 
that  the  exchange  of  gases  in  the  lungs  and  tissues  is  entirely  explained  by 
the  diffusion  of  the  gases  from  points  of  high  tension  to  points  of  low  ten- 
sion, and  that  the  membranes  interposed  are  entirely  passive  in  the  process 
has  not  passed  unchallenged.  Certain  observers  (Bohr,  Haldane,  and  Smith)  f 
claim  that  the  tension  of  the  oxygen  in  the  arterial  blood  may  be  higher  than 
the  pressure  of  oxygen  in  the  alveolar  air.  In  a  recent  discussion  of  the  sub- 
ject Haldane  §  admits  that  the  exchange  of  CO2  is  controlled  entirely  by- 
physical  diffusion,  but  he  brings  forward  some  facts  which  demonstrate,  in  his 
opinion,  that  the  oxygen  under  certain  unusual  conditions  may  be  secreted 
from  the  alveolar  air  into  the  blood  through  the  agency  of  the  epithelial  cells 
of  the  lungs.  The  condition  on  which  he  lays  emphasis  is  that  of  diminished 
oxygen-pressure  in  the  alveolar  air,  such  as  occurs  at  high  altitudes.  The  dis- 
turbances produced  at  these  altitudes,  so-called  mountain  sickness,  are  now 
recognized  to  be  due  to  lack  of  oxygen.  Those  who  live  for  some  time  under 

*  This  conclusion  is  doubted  by  some  observers,  see  Barcroft,  "Respirat- 
ory Function  of  the  Blood,"  1914,  p.  165. 

t"Skandinavisches  Archiv  f.  Physiologic,"  16,  402,  1896. 

j  See  Haldane  and  Smith,  "Journal  of  Physiology,"  20,  497,  1896. 

\  Haldane,  General  discussion  in  "Organism  and  Environment,  etc.," 
New  Haven,  1917. 

44 


690  PHYSIOLOGY    OF    RESPIRATION. 

such  conditions  gradually  become  acclimated,  and  Haldane  believes  that  the 
essential  factor  in  the  acclimatization  consists  in  the  assumption  of  a  secretory 
activity  for  oxygen  upon  the  part  of  the  lungs.  His  reason  for  this  view  is  the 
discovery  that  the  oxygen-pressure  in  the  arterial  blood  under  these  conditions 
is  greater  than  the  oxygen-pressure  in  the  alveolar  air.  The  oxygen-pressure 
of  the  blood  was  estimated  by  means  of  his  carbon  monoxid  method.  When 
an  individual  is  allowed  to  breathe  a  mixture  of  oxygen  and  carbon  monoxid  in 
which  the  latter  is  present  in  small  but  known  percentage,  the  hemoglobin 
combines  partly  with  the  oxygen  and  partly  with  the  carbon  monoxid  in  defi- 
nite proportions.  After  equilibrium  has  been  established  to  this  mixture  the 
percentage  saturation  of  the  hemoglobin  with  carbon  monoxid  may  be  deter- 
mined upon  a  sample  of  blood,  and  from  this  figure  the  percentage  saturation 
with  oxygen  may  be  estimated.  Experiments  of  this  kind  made  at  high  alti- 
tudes (Pike's  Peak,  14,100  feet)  indicated  that  the  oxygen  pressure  in  the  blood 
was  35  nuns,  greater  than  in  the  alveolar  air.  As  collateral  evidence  he  cites  the 
case  of  the  swim-bladder  in  deep-sea  fishes.  The  gas  in  this  bladder  is  known 
to  be  nearly  pure  oxygen,  and  it  may  exist  under  a  pressure  of  100  atmospheres, 
although  in  the  blood  of  the  fishes  the  oxygen-pressure  cannot  exceed  £  to  jV 
of  an  atmosphere. 


CHAPTER  XXXVII. 
INNERVATION  OF  THE  RESPIRATORY  MOVEMENTS. 

The  nervous  supply  to  the  respiratory  muscles  is  received  from 
a  number  of  nerves,  the  nervous  machinery  being  widely  dis- 
tributed in  the  brain  and  cord.  The  most  important  of  the  motor 
nerves  of  respiration  is  the  phrenic,  which  supplies  the  diaphragm 
and  originates  from  the  fourth  and  fifth  cervical  spinal  nerves. 
The  N.  accessorius  and  branches  of  the  cervical  and  brachial 
plexus  innervate  the  muscles  of  the  neck  and  shoulder  which  are 
concerned  in  inspiration;  the  intercostals  innervate  the  muscles  of 
the  thorax  and  abdomen,  while  branches  of  the  lumbar  plexus  send 
fibers  to  the  muscles  of  the  groin.  Moreover,  the  facial  sends 
motor  branches  to  the  muscles  of  the  nose  and  the  vagus  supplies 
the  muscles  of  the  larynx.  All  of  these  muscles  belong  to  the 
skeletal  group  and  are  under  voluntary  control.  Under  normal 
conditions,  however,  this  entire  respiratory  apparatus  works 
rhythmically  without  voluntary  control,  in  alternate  inspirations 
and  expirations,  all  the  inspiratory  muscles  contracting  together, 
and  all  the  expiratory  muscles  together  in  their  turn  when  the 
expirations  are  active.  The  co-ordinated  activity  of  such  an  ex- 
tensive mechanism  is  explained  by  the  existence  of  a  respiratory 
center  in  the  medulla  oblongata. 

The  Respiratory  Center.— The  discovery  of  the  location  of  the 
respiratory  center  was  due  mainly  to  the  experiments  of  two  French 
physiologists,  Legallois  and  Flourens.  The  latter  placed  the 
center  in  the  medulla  at  the  level  of  the  calamus  scriptorius,  and 
described  it  as  a  very  small  area  or  spot,  which  he  designated  at  first 
as  the  vital  knot  (n&ud  vital)  under  the  mistaken  impression  that 
it  formed,  as  it  were,  a  central  or  focal  point  of  the  motor  system. 
It  has  since  been  shown  that  this  center,  like  the  vasomotor 
center,  is  bilateral.  If  the  medulla  is  cut  through  in  the  mid- 
line  the  respirations  may  proceed  in  a  normal  manner.  The  center 
consists  of  two  parts,  each  connected  primarily  with  the  muscula- 
ture of  its  own  side.  Each  half  occupies  an  area  that  lies  some 
distance  lateral  to  the  mid-line  and  beneath  the  floor  of  the  medulla 
at  the  general  level  of  the  calamus.  According  to  Gierke,*  the  area 

*  Gierke,  "Archiv  f.  die  gesammte  Physiologic,"  7,  583,  1873;  and  "Cen- 
tralblatt  f.  d.  med.  Wissenschaften,"  No.  34,  1885. 

691 


692  PHYSIOLOGY    OF    RESPIRATION. 

extends  in  rabbits  from  a  point  3  or  4  mms.  in  front  of,  to  a  point 
2  or  3  mms.  posterior  to  the  calamus.  No  especial  group  of  cells 
can  be  found  in  this  region  sufficiently  separated  anatomically  to 
make  it  probable  that  they  constitute  the  center  in  question.  The 
region  has  been  delimited  by  vivisection  experiments  only,  and, 
according  to  Gierke,  corresponds  in  location  to  the  position  of  the 
solitary  bundle  (tractus  solitarius).  According  to  Mislawsky,* 
it  lies  near  the  mid-line  in  the  formatio  reticularis,  while  Gadf  give^ 
it  a  relatively  large  area  in  the  lateral  portion  of  the  formatio 
reticularis,  the  continuation  into  the  medulla  of  the  lateral  horn  of 
the  gray  matter  of  the  cord.  Destruction  of  these  areas  or  section 
of  the  cord  anywhere  between  this  region  and  the  origin  of  the 
phrenic  nerve  cuts  off  the  respiratory  movements,  except  those  of 
the  nose  and  larynx,  and  causes  death.  The  rapid  death  from 
injuries  to  the  cord  or  medulla  in  this  region — from  hanging,  for 
instance — is  explained  by  the  effect  upon  the  respiratory  center 
or  its  connections. 

There  is  no  doubt  that  the  respiratory  center  in  man  occupies  the  same 
general  position  as  in  the  other  mammals.  There  is  on  record  a  casej  in 
which  sections  were  made  of  the  medulla  in  a  new-born  infant.  On  delivery 
it  was  necessary  to  puncture  the  cranium  and  remove  the  brain.  The  child 
still  lived  and  the  medulla  was  cut  across  with  scissors.  A  section  at  the 
posterior  end  of  the  calamus  stopped  the  respirations  immediately,  while 
one  somewhat  anterior  had  failed  to  have  this  effect. 

The  general  idea  of  the  connections  of  this  center  with  the  respir- 
atory muscles  may  be  described  as  follows:  The  respiratory  fibers 
arising  in  the  center  pass  down  the  cord,  probably  in  the  antero- 
lateral  columns,  and  end  in  the  gray  matter  of  the  cord  at  the 
different  levels  at  which  the  motor  nuclei  of  the  respiratory  nerves 
are  situated.  Whether  the  connection  between  the  respiratory 
center  and  the  spinal  motor  nuclei  is  made  by  one  or  by  a  series  of 
neurons  is  not  known,  but  we  may  assert  that  the  nerve  path 
from  the  respiratory  center  to  the  respiratory  muscles  must  be 
composed  of  at  least  two  neurons.  According  to  this  conception, 
the  impulses  of  inspiration  and  expiration  for  the  entire  respira- 
tory mechanism  originate  in  the  medullary  center  and  are  thence 
distributed  in  a  co-ordinated  way  to  the  lower  motor  centers  in 
the  cord,  or,  in  the  case  of  the  nose  and  larynx,  to  the  motor 
centers  of  the  vagus  and  facial. 

Spinal  Respiratory  Centers. — At  different  times  various  authors 
(Brown-Sequard,  Langendorff,  et  aL)  have  insisted  that  there  exist  one  or 
more  spinal  respiratory  centers,  and  that  the  medullary  center  has  not  the 

*  Mislawsky,  "Centralblatt  f.  die  med.  Wissenschaften,"  No.  27,  1885. 

t  Gad,  "Archiv  f.  Physiologic,"  1893,  p.  75. 

j  See  Kehrer,  "Monatshefte  f.  prakt.  Dermatol.,"  28,  450,  1892. 


INNERVATION    OF    THE    RESPIRATORY    MOVEMENTS.  693 

commanding  importance  indicated  in  the  above  description.  The  fact  that, 
when  the  medulla  or  cervical  cord  below  the  medulla  is  cut,  the  animal  at 
once  ceases  to  breathe  is  explained  by  these  authors  on  the  assumption  that 
the  operation  causes  a  prolonged  inhibition  of  the  underlying  spinal  centers. 
They  state  that  young  animals,  especially  if  made  hyperirritable  by  the  in- 
jection of  strychnin,  may  continue  to  breathe  after  section  of  the  cord  below 
the  medulla.  This  point  of  view,  however,  has  not  prevailed  in  physiology. 
Other  operations  on  the  cord  or  brain  are  not  attended  by  such  profound 
inhibition,  and  indeed  Porter  and  Miihlberg  have  shown*  that,  if  half  of  the 
cord  alone  is  cut,  the  movements  of  the  diaphragm  on  that  side  are  permanently 
paralyzed.  It  is  entirely  conceivable  that  under  exceptional  conditions 
the  lower  neurons,  the  direct  motor  centers  of  the  respiratory  muscles,  might 
be  made  to  act  rhythmically,  since  during  life  they  have  been  rhythmically  stim- 
ulated from  the  medullary  center  ;  but  the  evidence  at  present  is  altogether 
against  any  distinct  physiological  independence  on  the  part  of  those  neurons. 

The  Automatic  Activity  of  the  Respiratory  Center. — The 

constant  activity  of  the  respiratory  center  throughout  life  suggests 
the  question  as  to  its  automaticity.  Is  it  automatic  like  the  heart? 
That  is,  are  the  stimuli  discharged  from  it  produced  within  its  own 
cells  as  a  result  of  its  own  metabolism  under  the  normal  conditions 
of  circulation?  Or,  on  the  other  hand,  is  it,  like  most  of  the  motor 
nuclei  of  the  central  nervous  system,  only  a  reflex  center,  its  motor 
discharges  being  dependent  upon  impulses  received  from  other 
neurons  by  way  of  the  sensory  paths?  Obviously  the  only  way  to 
answer  such  a  question  directly  is  to  isolate  the  center  from  all 
afferent  paths  and  leave  it  connected  with  the  respiratory  muscles 
only  by  motor  nerves.  If  under  such  conditions  the  respiratory 
rhythm  continues  the  center  may  be  regarded  as  essentially  auto- 
matic, however  susceptible  it  may  be  to  reflex  influences.  A  close 
approximation  at  least  has  been  made  to  such  an  experiment. 
Rosenthal  finds  that  rhythmical  respiratory  movements  continue 
after  the  following  operations :  first,  section  of  the  brain  at  the  cor- 
pora quadrigemina  to  cut  off  influences  from  the  cerebrum,  thala- 
mus,  and  midbrain;  second,  section  of  the  vagi,  to  shut  off  afferent 
impulses  from  the  viscera,  especially  from  the  lungs;  third,  section 
of  the  cord  at  the  seventh  cervical  vertebra  to  exclude  sensory 
influences  through  all  the  underlying  posterior  roots;  and,  fourth, 
section  of  the  posterior  roots  of  the  cervical  spinal  nerves.  The 
medulla  with  its  respiratory  center  was  thus  isolated  from  all 
afferent  impulses  except  such  as  might  enter  through  the  fifth, 
seventh,  eighth,  and  ninth  cranial  nerves.  Since  under  these  con- 
ditions the  center  continued  to  act  rhythmically  we  may  draw 
the  probable  conclusion  that  it  is  essentially  automatic,  and  that 
it  probably  possesses  an  intrinsic  rhythmical  activity  resembling 
that  of  the  heart.  An  interesting  supplementary  experiment 
upon  this  point  is  reported  by  Winterstein.f  The  rhythmic 

*  "American  Journal  of  Physiology,"  4,  334,  1900. 
t  Winterstein,  "Pfliiger's  Archiv,"  138,  159,  1911. 


694 


PHYSIOLOGY    OF    RESPIRATION. 


activity  of  the  respiratory  center  has  been  referred  by  some  authors 
to  reflex  stimulation  of  the  center  by  sensory  impulses  arising  in 
the  respiratory  muscles  themselves.  To  exclude  this  possibility 
Winterstein  curarized  an  animal  to  immobilize  the  respiratory 
muscles,  and  then  divided  the  phrenic  nerve  and  connected  its 
central  stump  with  a  galvanometer.  Under  these  conditions  the 
galvanometer  recorded  rhythmic  action  currents,  which  demon- 
strated that  the  respiratory  center  was  sending  out  rhythmic 
discharges  of  nerve  impulses. 

Reflex  Stimulation  of  the  Center. — According  to  the  results 
of  numerous  observers,  stimulation  of  any  of  the  sensory  nerves 
of  the  body  may  affect  the  rate  or  the  amplitude  of  the  respiratory 
movements.  This  experimental  result  is  confirmed  by  our  own 
experience,  since  every  one  must  have  noticed  that  the  respiratory 
movements  are  readily  affected  by  strong  stimulation  of  the  cutane- 
ous nerves — a  dash  of  cold  water, 
for  example — as  well  as  through 
the  nerves  of  sight  and  hearing. 
In  addition,  emotional  states  are 
apt  to  be  accompanied  by  notice* 
able  changes  in  the  respirations, 
and  corresponding  to  this  fact 
experiment  shows  that  stimula- 
tion of  certain  portions  of  the  cor- 
tex and  midbrain  gives  distinct 
effects  upon  the  respiratory  cen- 
ter. We  must  assume,  therefore, 
that  this  center  is  in  connection 
with  the  sensory  fibers  of  per- 
haps all  of  the  cranial  and  spinal 
nerves,  and  is  influenced  also  by 
intracentral  paths  passing  from 
cerebrum  to  medulla,  paths  which 
are  efferent  as  regards  the  cere- 
brum, but  afferent  a»  regards  the 
medulla.  As  stated  above,  the 
effect  of  these  sensory  nerves 

upon  the  activity  of  the  respiratory  center  is  varied ;  the  rate  may 
be  changed  together  with  an  increased  or  decreased  amplitude,  the 
inspirations  and  expirations  may  each  be  increased,  or  one  phase 
may  be  affected  more  markedly  than  the  other.  In  general,  how- 
ever, experimental  stimulation  of  a  sensory  nerve  trunk  which  con- 
tains cutaneous  fibers  gives  one  of  two  effects :  either  a  stimulating 
action,  manifested  by  quicker,  stronger  inspirations  and  active  ex- 
pirations, or  an  inhibitory  effect,  in  which  the  respirations  cease 


Fig.  276. — To  show  the  augmenta- 
tion of  the  respiratory  movements  caused 
by  stimulation  of  the  sciatic  nerve.  Ex« 
periment  upon  a  rabbit. 


INNERVATION    OF   THE    RESPIRATORY    MOVEMENTS.  695 

altogether  or  become  slower  and  more  feeble  (Figs.  276  and  277) . 
If  in  this,  as  in  other  similar  cases,  we  assume  that  the  two  oppo- 
site effects  are  produced  by  different  nerve  fibers  we  may  speak  of 
sensory  fibers  which  have  a  stimulating  or  augmenting  effect,  and 
of  those  that  have  an  inhibiting  influence  on  the  center,  or  following 
the  terminology  used  in  the  case  of  the  vasomotor  center,  we  may 
speak  of  respiratory  pressor  and  respiratory  depressor  fibers.  It  is 
quite  probable  that  these  fibers  have  other  functions, — that  is,  they 
are  not  distributed  exclusively  to  the  respiratory  center.  A  cuta- 
neous fiber,  which  through  its  central  chain  of  neurons  eventually 
ends  in  the  cortex  cerebri  and  gives  us  a  sensation  of  pain,  may 


"Fig.  277. — To  show  the  inhibition  of  the  respiratory  movements  in  a  rabbit  ^  due  to 
stimulation  of  the  central  end  of  the  vagus.  The  respiratory  movements  in  this  case, 
before  and  after  stimulation,  were  forced,  owing  to  the  fact  that  both  vagi  were  cut. 

by  collateral  connections  affect  also  the  medullary  center  and  pro- 
duce effects  upon  the  heart,  blood-vessels,  and  respirations. 

The  Special  Relations  of  the  Afferent  Fibers  of  the  Vagus 
to  the  Center. — Although  the  sensory  nerves  in  general  exert  a 
reflex  effect  upon  the  respiratory  center,  experimental  work  has 
shown  that  the  sensory  fibers  distributed  along  the  respiratory 
passages  from  the  anterior  nares  to  the  alveoli  have  a  specially 
important  relation  to  this  center.  This  fact  is  most  clearly  shown 
in  the  case  of  the  sensory  fibers  of  the  vagus,  which  are  distributed 
to  the  lungs  themselves.  If  the  two  vagi  are  cut  in  the  neck  the 
respiratory  movements  are  at  once  altered  in  character;  they 
show  a  much  slower  rhythm  and  greater  amplitude  (Fig.  278). 
The  inspirations  especially  are  deeper  and  longer,  with  something 
of  a  pause  at  the  end.  When  only  one  vagus  is  cut  an  intermediate 
effect  may  be  obtained,  the  respiratory  movements  may  be  slowed 
somewhat  and  slightly  deepened;  but  the  striking  effect  is  observed 


696  PHYSIOLOGY    OF    RESPIRATION. 

only  after  section  of  both  nerves.  This  result  is  not  a  temporary 
one  due  to  the  stimulation  of  cutting,  but  is  permanent,  and  there- 
fore we  may  conclude  that  some  influence  has  been  cut  off  which 
normally  keeps  the  respiratory  movements  at  a  more  rapid  rate. 
Experiment  has  shown  that  this  influence  consists  in  the  tonic 
action  of  sensory  fibers  contained  in  the  vagus  and  distributed 
to  the  lungs.  It  is  the  constant  effect  of  these  fibers  on  the  respira- 
tory center  which  maintains  the  normal  rhythm;  when  they  are 
severed  the  center  drops  into  a  slower,  unregulated  rhythm.  Ex- 
periment has  shown,  also,  that  when  the  central  stump  of  the 
divided  vagus  is  stimulated  artificially  the  respiratory  center  is 
affected,  as  indicated  by  the  respiratory  movements,  in  a  variety 
of  ways,  depending  upon  the  strength  of  the  stimulus  and  the 
condition  of  the  center.  The  two  results  which  are  most  constantly 
.obtained  and  which  may  therefore  be  especially  emphasized  are  as 
follows:  first,  with  weak  stimuli  the  inspiratory  movements  are  in- 
hibited partially  or  completely,  giving  either  smaller  movements  or, 
in  a  condition  of  narcosis,  complete  cessation  of  respirations,  with 


X 


Fig.  278. — To  show  the  effect  of  section  of  the  vagi  on  the  respiratory  movements 
(rabbit).  The  right  vagus  was  cut  at  x  and  caused  a  slight  augmentation  and  slowing 
of  the  movements.  The  left  vagus  was  cut  at  xx  and  caused  first  a  short  inhibition  (due 
to  mechanical  stimulation)  which  was  then  followed  by  the  typical  slow  and  deep  respi- 
rations seen  under  these  conditions. — (Dawson.) 

the  thorax  in  the  stage  of  passive  expiration  (Fig.  277),  or,  second, 
the  rate  of  the  inspiratory  movements  may  be  increased  and  this 
may  end  finally  in  an  inspiratory  standstill, — that  is,  the  respiratory 
movements  cease  with  the  chest  in  an  inspiratory  position  (Fig.  279), 
the  inspiratory  muscles  being  in  a  condition  of  tetanic  contraction. 
When  both  the  inspiratory  and  expiratory  muscles  are  considered, 
the  variety  of  effects  that  may  be  obtained  from  stimulation  of  the 
afferent  fibers  of  the  vagus  is  perplexing,  especially  with  strong 


INNERVATION    OF    THE    RESPIRATORY    MOVEMENTS.  697 

stimuli,  and  has  led  to  much  difference  of  opinion  among  investi- 
gators.* The  two  main  effects  described  above  are  usually  inter- 
preted to  mean  that  the  vagus  contains  two  kinds  of  sensory  fibers 
which  are  distributed  to  the  lungs  and  act  normally  on  the  respira- 
tory center.  These  are:  (I)  The  inspiratory  fibers,  whose  effect 
is  to  increase  the  rate  of  inspiratory  discharge  from  the  respiratory 
center;  therefore  to  quicken  the  rate.  (II)  The  expiratory  (or 
inspiratory  inhibiting)  fibers,  whose  effect  is  to  inhibit  the  inspira- 
tory discharges,  partially  or  .completely.  Some  authors  find  it 
simpler  to  assume  only  one  kind  of  sensory  fiber  and  to  explain  the 
different  results  by  a  difference  in  the  nature  of  the  stimulus  or 


Fig.  279. — To  illustrate  the  inspiratory  effect  from  stimulation  of  the  central  end  of 
the  vagus.  The  downstroke  represents  inspiration;  the  upstroke,  expiration.  During 
the  period  of  stimulation  the  respirations  are  increased  in  frequency  and  the  chest  remains 
in  a  condition  of  inspiration. — (Lewandowsky.) 

in  the  condition  of  the  center;  but  it  seems  advisable  at  present, 
in  accordance  with  the  doctrine  of  specific  nerve  energies,  to  hold 
to  the  view  of  two  varieties. 

Influence  of  the  Inspiratory  and  the  Inhibitory  Fibers  of 
the  Vagus  on  the  Normal  Respirations. — It  is  assumed  that 
these  two  sets  of  fibers  are  in  constant  activity  and  keep  the  re- 
spiratory rate  more  rapid  than  it  would  be  otherwise.  Hence  the 
slowing  and  deepening  of  the  respirations  when  the  vagi  are  cut. 
The  way  in  which  these  sensory  fibers  are  stimulated  normally  was 
referred  by  Hering  and  Breuer  to  the  alternate  expansion  and 
collapse  of  the  lungs.  Each  inspiration  stimulates  the  inhibitory 
fibers  in  consequence  of  the  expansion  of  the  lungs,  and  thus  cuts 
short  the  inspiration,  prematurely,  as  it  were.  So  at  each  expira- 
tion the  collapse  of  the  lungs  stimulates  the  inspiratory  fibers  and 
brings  on  an  inspiration  sooner  than  would  otherwise  occur.  In 
this  way  the  respiratory  rate  is  kept  automatically  at  an  accel- 
erated rhythm.  This  hypothesis  has  been  much  discussed 
and  many  efforts  have  been  made  to  prove  or  disprove  it  by 
means  of  experiments.  The  result  of  this  work  on  the  whole 


698 


PHYSIOLOGY    OF    RESPIRATION. 


tends  to  show  that  the  hypothesis  is  essentially  correct.  Two 
kinds  of  afferent  fibers  exist  in  the  vagus,  one  of  which  is  stimu- 
lated by  expansion  of  the  lungs,  the  other  by  collapse.  This 
fact  is  shown  most  clearly  by  Einthoven's*  experiments  with 
his  string-galvanometer.  When  the  vagus  nerve  is  cut  high  in 
the  neck  and  is  then  connected  in  the  usual  way  with  the  string- 
galvanometer,  the  latter  shows  a  marked  action  current  through- 
out each  inspiration,  indicating,  therefore,  the  passage  of  a  series 
of  nerve  impulses  during  inspiration  (Fig.  280).  When  by  suction 
the  lungs  were  collapsed,  .another  electrical  variation  of  a  different 
character  was  produced,  indicating  the  existence  of  a  separate 
set  of  fibers  brought  into  action  by  the  diminution  in  volume  of 
the  lungs.  In  quiet  respirations  the  expiration  consists  in 
merely  a  passive  return  to  what  may  be  called  the  neutral  or 
normal  volume  of  the  lungs,  and  in  this  movement  it  is  probable 
that  the  inspiratory  fibers  are  not  affected,  being  stimulated 
only  by  an  active  expiration.  We  may  assume,  therefore, 
with  Gad  that  the  normal  rate  of  respirations  is  maintained 


Fig.  280. — To  show  the  electrical  changes  in  the  afferent  fibers  of  the  vagus  nerve 
caused  by  the  respirations  and  the  heart  beats:  V,  The  electrovagogram,  the  large  waves 
are  electrical  oscillations  synchronous  with  the  respiratory  movements.  The  smaller  ones 
are  electrical  changes  synchronous  with  the  heart  beats;  P,  Mechanical  record  of  the 
respiratory  movements,  ascent  of  curve,  inspiration;  C,  Mechanical  record  of  pulse  beats. 
(From  Einthoven.) 


by  the  action  of  the  inhibitory  fibers  alone.  Each  inspiration 
is  cut  short  by  the  mechanical  stimulation  of  these  fibers,  but 
on  the  collapse  of  the  lungs  the  new  inspiration  is  due  to  a 
normal  discharge  from  the  inspiratory  center. 

Loewyf  nas  shown  by  an  ingenious  experiment  that  the  expansion  of 


the  lungs  is  the  factor  that  actually  stimulates  the  sensory  fibers  and  quickens 
for  a 

,  "Quarterly  Journal  of  Exp.  Physiology,"  1908,  1,  243;  also 
the  Physiological  Laboratory  of  the  University  of  Leyden," 


*  Einthoven, 
"Researches  of 
VII.,  1908. 

t  "Archiv  f.  die  gesammte  Physiologic,"  42,  273. 


INNERVATION    OF    THE    RESPIRATORY    MOVEMENTS.  699 

say,  the  right  side — was  then  opened  with  the  result  that  the  lung  collapsed, 
and,  owing  to  the  rapid  absorption  of  the  oxygen,  soon  became  practically 
solid.  The  respirations  (rabbit"1  showed  their  normal  rate — 66.  The  vagus 
nerve  on  the  left  side  was  then  cut  and  immediately  the  respirations  took 
on  the  character  usually  shown  when  both  vagi  are  severed, — respirations 
=  34.  Next  the  collapsed  right  lung  was  expanded  by  artificial  respiration, 
with  the  result  that  the  respiratory  rate  at  once  returned  to  normal. 

Respiratory  Reflexes  from  the  Larynx,  Pharynx,  and  Nose. 

— The  mucous  membrane  of  the  larynx  receives  its  sensory  fibers 
from  the  superior  laryngeal  nerve.  When  this  nerve  is  stimulated 
artificially  the  respirations  are  always  inhibited ;  the  chest  comes  to 
rest  in  the  position  of  passive  expiration.  The  same  effect  may  be 
obtained  from  the  sensory  fibers  of  the  glossopharyngeal  supplying 
the  pharynx,  and  indeed  a  temporary  inhibition  of  respirations 
occurs  through  this  nerve  during  every  act  of  swallowing.  The 
sensory  fibers  of  the  nasal  mucous  membrane  (trigeminal)  cause  a 
similar  reflex  inhibition  when  stimulated  by  injurious  or  so  called 
irrespirable  gases,  such  as  HC1,  Cl,  NH3,  SO2,  etc.  We  may  regard 
this  inhibitory  influence  exerted  by  the  sensory  fibers  distributed 
along  the  air  passages  as  a  protective  reflex  which  guards  the  lungs 
automatically  from  injurious  gases.  This  protective  action  is 
made  more  evident  by  the  fact  that,  together  with  the  cessation  of 
respirations,  the  glottis  is  reflexly  closed  by  contraction  of  the  ad- 
ductor muscles  and,  if  the  stimulation  is  strong,  even  the  bronchial 
musculature  may  be  contracted,  so  that  in  every  way  the  passage 
to  the  alveoli  is  made  more  difficult.  The  reflex  is,  of  course,  more 
or  less  temporary,  but  it  possesses  the  great  advantage  of  being 
automatic,  and  may  enable  the  animal  or  individual  to  escape 
unharmed  from  a  dangerous  locality  before  the  increasing  irritabil- 
ity of  the  respiratory  center  breaks  through  the  inhibition.  In 
special  cases  the  inhibition  may  last  for  an  unusually  long  time. 
Thus,  Fredericq  states  that  in  aquatic  birds  water  allowed  to  flow 
over  the  beak  so  as  to  penetrate  slightly  into  the  nostrils  brings 
about  an  inhibition  of  respirations  for  many  minutes.  There 
would  seem  in  this  case  to  be  a  special  adaptation  of  the  reflex  to 
the  needs  of  diving.  We  know  also  that  irritating  gases  or  foreign 
bodies  of  any  sort  that  enter  the  larynx  may  lead  to  a  coughing 
reflex, — that  is,  to  a  series  of  expiratory  blasts  which  have  a  pur- 
poseful end  in  the  expulsion  of  the  stimulating  object.  In  this  case 
there  is  not  simply  an  inhibition  of  the  inspiratory  movements, 
but  a  reflex  excitation  of  a  peculiar  type  of  expiratory  movemente. 
The  Voluntary  Control  of  the  Respiratory  Movements.— 
We  can  control  the  respiratory  movements  within  wide  limits,  make 
forced  or  feeble  inspirations  or  expirations,  accelerate  the  rhythm, 
or  completely  inhibit  the  respirations  in  any  phase.  If,  however, 
the  "breath  is  held," — that  is,  if  the  respiratory  movements  are 


700  PHYSIOLOGY    OF    RESPIRATION. 

inhibited  and  the  glottis  is  closed,  the  increasing  irritability  of 
the  respiratory  center  eventually  breaks  through  the  voluntary 
inhibition.  How  far  this  voluntary  control  is  based  upon  direct 
connections  between  the  cerebrum  and  the  respiratory  center  and 
how  far  it  depends  upon  voluntary  paths  to  the  separate  spinal 
nuclei  of  the  muscles  involved  cannot  be  discussed  profitably. 
The  Nature  of  the  Respiratory  Center. — The  respiratory 
center  located  in  the  medulla  oblongata  might  with  more  propriety 
be  designated  as  the  inspiratory  center.  Our  normal  respirations 
throughout  life  consist  of  an  active  inspiration  and  a  passive 
expiration.  It  is  the  co-ordinated  activity  of  the  inspirator}' 
muscles  that  is  characteristic  of  the  respiratory  movements.  The 
expiratory  muscles  come  into  action  only  occasionally  and  under 
special  conditions.  So  also  when  we  describe  the  respiratory 
center  as  essentially  automatic  we  refer  only  to  the  action  on 
the  inspiratory  muscles,  since  a  series  of  active  inspiratory  move- 
ments is  the  essential  feature  of  respiration.  Under  certain  con- 
ditions, however,  we  do  have  rhythmical  expiratory  movements, 
active  expirations.  Such  movements  may  occur  independently 
of  the  respirations  proper,  as  in  coughing  and  laughing,  or  in  the 
straining  movements  of  defecation,  micturition,  and  parturition; 
or  they  may  occur  as  an  integral  part  of  the  respirations,  as  in  the 
forced  movements  of  dyspnea.  Under  the  conditions  of  partial 
suffocation,  for  instance,  as  the  blood  becomes  more  and  more 
venous  the  respirations  increase  in  force  and  active  expirations 
appear.  It  becomes  a  question,  therefore,  as  to  the  existence  of 
what  might  be  called  an  expiratory  center,  a  group  of  nerve  cells 
controlling  the  co-ordinated  activity  of  the  expiratory  muscles. 
The  mere  fact  that  in  dyspnea  we  have  a  rhythmical  and  co-ordi- 
nated activity  of  these  muscles  seems  to  imply  the  existence  of  such 
a  center,  but  there  is  no  definite  experimental  knowledge  as  to  its 
location.  Assuming  that  there  is  such  a  center,  it  may  be  believed 
that  it  exists  in  the  medulla,  since  after  section  below  the  medulla 
there  is  no  evidence  of  the  occurrence  of  rhythmical  expiratory 
movements  even  in  extreme  conditions  of  venosity  of  the  blood. 
The  expiratory  center  may  or  may  not  be  located  in  the  same 
region  as  the  inspiratory  center,  but  the  following  general  char- 
acteristics may  be  assigned  to  it:  In  the  first  place,  it  is  not  auto- 
matic ;  at  least  not  under  normal  conditions.  In  the  second  place, 
its  activity  must  be  dependent  in  some  way  upon  that  of  the  in- 
spiratory center.  Even  our  most  violent  respiratory  movements 
show  an  orderly  sequence  of  inspiration  and  expiration, — and  we 
may  believe  that  the  action  of  the  expiratory  center  is  conditioned 
by  the  previous  discharge  of  the  inspiratory  center,  just  as  in  the 
heart  the  beat  of  the  ventricle  depends  upon  the  previous  systole 


INNERVATION    OF    THE    RESPIRATORY    MOVEMENTS.  701 

of  the  auricle.  That  an  active  expiration  is  not  caused  reflexly  by 
the  mechanical  expansion  of  the  lungs  seems  to  be  demonstrated 
by  the  fact  that  the  most  forcible  voluntary  inspiration  is  followed 
by  a  passive,  not  an  active  expiration.  Until  our  knowledge  is 
extended  by  further  experimental  work  we  may  consider  the  ex- 
piratory center  as  a  group  of  cells  connected  by  definite  paths  with 
the  expiratory  muscles  and  capable  of  being  stimulated  in  one  of  at 
least  four  general  ways:  (1)  In  special  reflexes,  such  as  coughing. 
(2)  By  voluntary  control  from  the  cerebrum,  as  in  straining.  (3) 
By  stimulation  through  afferent  fibers  from  the  skin,  especially  the 
pain  fibers.  (4)  By  the  action  of  an  increased  venosity  of  the  blood. 
Under  the  latter  two  conditions  it  is  possible  that  the  irritability 
of  the  center  is  so  increased  that  it  becomes  responsive  to  the  in- 
fluence of  the  inspiratory  center.  The  relations  of  the  inspiratory 
and  expiratory  centers  under  the  various  conditions  of  artificial 
stimulation  are  very  complex,  and  although  it  is  possible  to  rep- 
resent these  relations  more  or  less  completely  by  schemata  of  some 
sort  it  does  not  seem  advisable  at  present  to  seriously  consider 
such  hypotheses. 

The  Accessory  Respiratory  Centers  of  the  Midbrain. — Several  observers 
have  called  attention  to  the  existence  of  a  possible  accessory  respiratory  center 
in  the  midbrain  at  the  level  of  the  posterior  colliculus.  Martin  and  Booker 
found  that  stimulations  in  this  region  caused  a  marked  increase  in  the  rate 
of  inspiratory  movements  and  finally  a  standstill  in  inspiration, — that  is, 
a  complete  tetanic  contraction  of  the  inspiratory  muscles  lasting  during  the 
stimulation.*  Lewandowskyf  has  shown  that  section  of  the  brain  stem 
at  or  below  the  inferior  colliculi  causes  an  alteration  in  the  respiratory  rhythm 
similar  to  that  following  section  of  both  vagi.  After  cutting  through  the 
inferior  colliculi  further  sections  more  posteriorly  do  not  add  to  the  effect. 
He  considers  that  there  is  an  automatic  inhibitory  center  in  the  midbrain 
which  influences  continually  the  automatic  activity  of  the  medullary  center. 

The  Nature  of  the  Automatic  Stimulus  to  the  Respiratory 
Center. — We  have  accepted  the  view  that  the  respiratory  (inspira- 
tory) center  is  essentially  automatic,  although  very  sensitive  to 
reflex  stimulation.  The  further  question  arises  as  to  the  nature  of 
the  automatic  stimulus.  Inasmuch  as  the  activity  of  the  center 
controls  the  gaseous  exchanges  of  the  blood,  it  was  natural  perhaps 
for  physiologists  to  look  to  the  gases  of  the  blood  for  the  origin  of 
the  internal  stimulus.  Experiments  show  beyond  question  that 
the  condition  of  the  gases  in  the  blood  has  a  direct  and  marked 
influence  upon  the  activity  of  the  center.  If  for  any  reason  the 
blood  supplying  the  center  becomes  more  venous,  the  respirations 
are  increased  in  force  or  rate  or  both,  and  indeed  the  activity  of  the 
center  is  in  a  general  way  increased  in  proportion  to  the  venosity 

*  Martin  and  Booker,  "  Journal  of  Physiology,"  1,  370,  1878. 
t  "  Archiv  f.  Physiologic,"  1896,  489. 


702  PHYSIOLOGY    OF    RESPIRATION. 

of  the  blood.  On  the  other  hand,  if  the  blood  supplying  the  center 
is  more  arterialized  than  normal,  by  active  ventilation  of  the  lungs, 
for  instance,  the  center  acts  more  feebly  or  may  fail  to  act  altogether, 
giving  the  condition  known  as  apnea.  These  facts  may  be  accepted 
as  completely  demonstrated,  but  they  do  not  go  far  enough.  When 
we  speak  of  the  arterial  blood  being  more  venous  than  normal  we 
mean  that  it  contains  less  oxygen  and  more  carbon  dioxid  than 
normal  arterial  blood.  Which  of  these  conditions  serves  to  stimulate 
the  center,  and  which  may  be  regarded  as  the  constant  stimulus 
throughout  life?  Much  evidence  has  been  collected  to  show  that 
the  action  of  the  respiratory  center  is  increased  when  the  tension 
of  the  C02  in  the  blood  is  raised  without  altering  that  of  the  oxygen, 
and  that  a  similar  result  is  obtained,  but  much  less  readily,  if 
the  tension  of  oxygen  is  greatly  diminished  without  any  change 
in  that  of  the  carbon  dioxid,  so  that  it  must  be  admitted  that  a 
change  in  either  factor  may  act  as  a  stimulus.  Experiments,  how- 
ever, have  indicated  that  the  accumulation  of  the  CO2  is  much  the 
more  efficient  stimulus  of  the  two.*  Zuntz  reports  the  following 
interesting  experiments,  in  which  the  extent  of  the  respiratory 
movements  was  measured  by  the  amount  of  air  breathed  in  a 
minute.  In  one  series  the  amount  of  oxygen  in  the  air  breathed 
was  reduced.  This  change  did  not  affect  the  quantity  of  carbon 
dioxid  in  the  blood.  The  following  results  were  obtained: 

Normal  air volume  breathed  per  minute  =  7,325  to    9,000  c.c. 

Air  with  10  to  11.5  per 

cent,  oxygen "  "      =  8,166  to    9,428    " 

Air  with  8  to  10  per  cent. 

oxygen "  "      =  9,093  to  12,810    " 

A  reduction  of  one-half  of  the  oxygen  in  the  air  breathed  had  little 
effect  upon  the  respirations.  A  similar  conclusion  may  be  drawn 
from  Haldane's  experiments  f  with  carbon  monoxid.  He  found 
upon  breathing  mixtures  of  this  gas  that  no  distinct  effects  were 
observable  until  the  blood  was  about  one-third  saturated  with 
the  gas, — that  is,  had  lost  one-third  of  its  oxygen.  Haldane 
states  that  when  the  oxygen  in  the  air  breathed  is  reduced 
from  20.9  per  cent,  to  14  or  15  per  cent.,  a  concentration  of 
oxygen  in  which  an  ordinary  flame  will  be  extinguished,  there  is  no 
perceptible  disturbance  in  breathing.  If,  however,  a  further  re- 
duction is  made  suddenly  to  7  or  8  per  cent,  there  is  marked  panting 
and  the  lack  of  oxygen  in  the  blood  is  indicated  by  the  blue  color  of 
the  face.  If  the  diminution  in  oxygen  is  effected  gradually,  as 
happens,  for  example,  when  a  person  rebreathes  the  air  in  a 

*  See  Zuntz,  "Archiv  f.  Physiologic,"  1897,  379.     See  also  Friedlander 
and  Herter,  "Zeit.  f.  physiol.  Chemie,"  2,  99,  and  3,  19. 
t  Haldane,  "Journal  of  Physiology,"  18,  442,  1895. 


INNERVATION   OF   THE   RESPIRATORY    MOVEMENTS.  703 

confined  space  (provision  being  made  for  the  absorption  of  the 
CO2),  the  effect  on  breathing  may  be  so  slight  as  to  cause  no  dis- 
tress to  the  individual  so  that  he  may  continue  the  rebreathing  until 
a  sudden  loss  of  consciousness  ensues  from  the  lack  of  oxygen.  A 
similar  experience  is  recorded  by  balloonists  for  very  high  ascen- 
sions, 25,000  to  30,000  feet  (see  p.  714)  Zuntz's  experiments,  in 
which  the  CO2  in  the  air  breathed  was  increased,  while  the  oxygen 
remained  normal,  gave  quite  different  results,  as  follows: 

Normal  air volume  breathed  per  minute,    7,433  c.c. 

Air  of  20.2  per  cent.  O,  0.95  per  cent. 

CO2 "  "          "          "        9,060    " 

Air  of  18.06  per  cent.  O,  2.97  per  cent. 

CO2 "  "  "  "       11,326    " 

Air  of  18.42  per  cent.  O,  11.5  per  cent. 

CO2 "  "          "          "      32,464    " 

These  and  similar  results*  show  that  small  differences  in  the 
amount  of  the  carbon  dioxid  in  the  blood  have  a  distinct  effect 
upon  the  activity  of  the  respiratory  center.  The  trend  of  recent 
work  favors  the  view  that  the  normal  stimulus  to  the  respiratory 
center  is  the  carbon  dioxid.  When  this  substance  is  present  above 
a  certain  amount  or  tension  it  acts  as  a  stimulus,  directly  or  indi- 
rectly, and  gives  rise  to  the  moderate  movements  of  normal  in- 
spiration. If  the  tension  of  the  carbon  dioxid  is  increased,  the 
stimulus  becomes  stronger  and  leads  to  the  production  of  a  condi- 
tion of  hyperpnea  and  dyspnea.  On  the  other  hand,  if  for  any 
reason,  such  as  active  ventilation  of  the  lungs,  the  tension  of  the 
carbon  dioxid  in  the  blood  falls  below  a  certain  value,  estimated  by 
Zuntz  as  lying  between  19  and  24  mms.,  no  stimulation  occurs,  the 
center  is  in  a  condition  of  apnea  and  respiratory  movements  cease. 
Haldanef  has  laid  great  emphasis  upon  the  delicacy  of  the  reaction 
of  the  respiratory  center  to  any  change  in  the  carbon  dioxid  press- 
ure. The  reaction,  in  fact,  is  so  sensitive  that  under  quite  extreme 
conditions  the  concentration  of  carbon  dioxid  in  the  alveolar  air  is 
kept  nearly  constant.  In  muscular  exercise,  for  example,  there  may 
be  a  large  output  of  carbon  dioxid  to  the  blood,  but  the  resulting 
increase  in  carbon  dioxid  pressure  so  stimulates  the  respiratory 
center  that  there  is  a  corresponding  augmentation  in  the  breathing, 
the  alveolar  space  is  more  thoroughly  ventilated,  and  the  concen- 
tration of  C02  in  the  alveolar  air,  and  consequently  in  the  arterial 
blood,  shows  but  little  change.  The  average  concentration  of  CO2 
in  the  alveolar  air  is  5.5  per  cent.  An  increase  of  as  little  as  0.2 
per  cent,  will  be  attended  by  a  doubling  of  the  volume  of  respira- 
tion. Accepting  the  view  that  the  carbon  dioxid  of  the  blood  con- 

*  See  Haldane  and  Priestley,  "Journal  of  Physiology,"  32,  225,  1905. 
t  Haldane,  "  Organism  and  Environment,"  1917. 


704  PHYSIOLOGY    OF    RESPIRATION. 

stitutes  the  normal  stimulus  to  the  respiratory  center  and  that  the 
activity  of  this  center  varies  proportionately  to  the  concentration  of 
the  carbon  dioxid  in  the  blood,  the  question  has  arisen  whether  the 
carbon  dioxid  acts  directly  as  a  stimulus  or  in  virtue  of  its  effect 
in  increasing  the  acidity  or  hydrogen  ion  concentration  of  the 
blood.  The  CO2  in  solution  forms  carbonic  acid,  H2CO3,  which  dis- 
sociates to  yield  hydrogen  ions.  Acids  added  to  the  blood  experi- 
mentally or  formed  in  the  body,  as  in  conditions  of  acidosis,  stimu- 
late the  center,  and  a  number  of  observers*  have  concluded,  there- 
fore, that  the  stimulus  to  the  center  is,  in  reality,  the  hydrogen-ion 
content  of  the  blood.  An  increase  in  carbon  dioxid  concentration 
such  as  occurs  in  muscular  exercise  would  tend  to  increase  the  hy- 
drogen-ion concentration  and  thus  its  stimulating  effect  is  explained. 
The  mechanism  works  automatically  in  the  direction  of  keeping  the 
reaction  of  the  blood  normal,  since  an  increase  of  acidity  by  stimu- 
lating the  center  and  causing  an  increased  ventilation  of  the  lungs 
tends  to  reduce  the  carbon  dioxid  pressure.  In  correspondence 
with  this  conclusion  it  is  found  that  in  acidosis  caused  by  an  increase 
in  the  fixed  acids  of  the  blood  there  is  a  noticeable  diminution  in  the 
carbon  dioxid  pressure  in  the  alveolar  air.  In  fact,  diminished  car- 
bon dioxid  pressure  in  the  alveolar  air  has  been  considered  as  one 
of  the  diagnostic  indications  of  a  condition  of  acidosis.  f  While 
there  can  be  no  doubt  of  the  general  fact  that  the  activity  of  the 
respiratory  center  is  sensitive  to  the  reaction  or  hydrogen-ion  con- 
centration of  the  blood,  and  that  in  consequence  this  center,  by  its 
influence  upon  the  breathing  and  the  composition  of  the  alveolar  air, 
serves  to  regulate  the  normal  reaction  of  the  blood,  there  is  still 
some  question  as  to  whether  the  effect  of  carbon  dioxid  upon  the 
center  is  wholly  due  to  its  influence  in  raising  the  hydrogen-ion  con- 
centration. In  some  direct  experiments  made  upon  the  isolated 
mammalian  medulla  perfused  with  defibrinated  blood  t  it  was  found, 
in  accordance  with  the  above  view,  that  any  increase  in  the  al- 
kalinity of  the  blood  tends  to  depress  the  activity  of  the  respira- 
tory center,  and  vice  versa.  But  it  is  also  stated  that  a  high  press- 
ure of  carbon  dioxid  in  the  perfused  blood  stimulates  the  center  to  a 
greater  degree  than  a  blood  of  the  same  hydrogen-ion  concentra- 
tion, but  with  a  low  tension  of  carbon  dioxid.  This  last  result 
indicates  that  the  carbon  dioxid  may  have  a  specific  stimulating 
effect  on  the  center;  but  whatever  may  be  its  mode  of  action,  it 
seems  certain  that  the  concentration  of  carbon  dioxid  in  the  blood 
controls  the  activity  of  the  respiratory  center  under  normal  condi- 
tions. Lack  of  oxygen,  as  we  have  seen,  may  also  stimulate  the 

*  Haldane,  loc.  tit.;  Winterstein,  "Pfliiger's  Archiv,"  138,  167,  1911. 
t  Marriott  and  Howland. 

j  Hooker,  Wilson,  and  Connett,  "American  Journal  of  Physiology/'  43, 
351,  1917. 


INNERVATION    OF   THE    RESPIRATORY    MOVEMENTS.  705 

center,  but  this  reaction  is  nothing  like  so  sensitive  as  that  due  to 
increase  of  carbon  dioxid.  The  oxygen  pressure  must  be  reduced  to 
a  very  noticeable  extent  before  accelerated  respirations  are  ob- 
tained. It  has  been  suggested  that  the  effect  of  reduced  oxygen 
pressure  upon  the  center  is,  in  reality,  simply  an  acid  effect.  The 
acids  formed  in  the  body  as  a  result  of  functional  activity  are  usu- 
ally supposed  to  be  removed  by  oxidation.  If  the  supply  of  oxygen 
is  markedly  deficient,  this  removal  may  be  incomplete  with  a  conse- 
quent increase  in  the  fixed  acids  and  hydrogen-ion  concentration 
of  the  blood. 

This  explanation  enables  us  to  understand  also  some  interest^ 
ing  results  of  the  effect  of  breathing  oxygen.  When  one  holds  his 
breath  the  carbon  dioxid  tension  in  the  blood  increases,  and  event- 
ually the  stimulus  becomes  so  strong  that  respirations  ensue  in 
spite  of  the  strongest  effort  to  inhibit  them.  This  "breaking  point" 
is  reached*  in  23  to  77  seconds  when  the  carbon  dioxid  in  the  alve- 
oli of  the  lungs  has  attained  a  concentration  of  6.2  to  7.5  per  cent., 
and  the  oxygen  is  reduced  to  9  to  11  per  cent.  If  before  holding 
the  breath  the  lungs  are  filled  with  oxygen  by  taking  several  breaths 
of  the  pure  gas,  the  breaking  point  may  be  prolonged  to  as  much  as 
160  seconds,  and  one  observer  (Vernon)  reports  that  if  the  lungs 
are  first  thoroughly  aerated  by  forced  breathing,  so  as  to  wash  out 
the  carbon  dioxid  in  the  alveoli,  and  at  the  end  pure  oxygen  is 
breathed  in,  the  breaking  point  may  be  deferred  as  long  as  eight 
minutes.  Evidently,  therefore,  an  accumulation  of  carbon  dioxid 
in  the  blood,  as  indicated  by  the  composition  of  the  alveolar  air, 
is  less  efficient  as  a  stimulus  to  the  center  when  an  adequate  supply 
of  oxygen  is  provided,  and  this  fact  may  be  explained  on  the  hy- 
pothesis that  the  oxygen  prevents  the  accumulation  of  the  acid 
products  of  metabolism. 

A  further  problem  in  connection  with  the  action  of  the  respiratory  center 
is  the  cause  of  its  rhythmic  activity.  The  underlying  mechanism  of  this 
rhythmicity  is  obscure,  but  it  is  possible  that  in  this  instance,  as  in  the  case  of 
the  heart-muscle,  the  property  is  dependent  in  some  way  upon  the  normal  bal- 
ance of  calcium,  potassium,  and  sodium  in  the  blood.  Variations  in  the  con- 
centration of  these  elements  cause  marked  changes  in  the  rhythmicity.  f 

The  Cause  of  the  First  Respiratory  Movement. — The  mam- 
malian fetus  under  normal  conditions  makes  no  respiratory  move- 
ments while  in  utero.  After  birth  and  the  interruption  of  the  pla- 
cental  circulation  the  first  breath  is  taken.  The  cause  of  this 
sudden  awakening  to  activity  on  the  part  of  the  respiratory  center 
must  be  closely  connected,  if  not  identical  with,  the  cause  of  the 

*  Hill  and  Flack,  "Journal  of  Physiology,"  37,  77,  1908. 
t  Hooker,  "American  Journal  of  Physiology,"  31,  1913,  "Proceedings  of 
the  American  Physiological  Society." 

45 


706  PHYSIOLOGY    OF    RESPIRATION. 

automatic  activity  of  the  center  throughout  life.  Two  or  perhaps 
three  views  have  been  held  regarding  its  immediate  cause:  (1) 
That  it  is  due  to  the  increased  venosity  of  the  blood  brought  about 
by  the  interruption  of  the  placental  circulation;  (2)  that  it  is  due  to 
stimulation  of  the  skin  by  handling,  drying,  etc.;  (3)  that  it  is  due 
to  a  combination  of  these  causes.  Preyer  has  shown  that  stimula- 
tion of  the  skin  of  the  fetus  while  in  utero  and  with  the  placental 
circulation  intact  sufficies  to  cause  respiratory  movements.  Cohn- 
stein  and  Zuntz*  have  shown  that  interruption  of  the  placental 
circulation  while  the  fetus  is  kept  bathed  in  the  amniotic  liquid  also 
brings  about  respirations.  Since  both  of  these  events  occur  normally 
at  birth,  we  may  believe  that  each  aids  in  causing  the  first  respira- 
tion, and  indeed  it  may  be  necessary  at  times  deliberately  to  in- 
crease the  stimulation  of  the  skin  in  order  to  bring  on  respiratory 
movements.  If  the  two  causes,  stimulation  through  the  nerves  and 
stimulation  through  the  blood,  normally  co-operate,  it  may,  how- 
ever, be  said  that  the  essential  cause,  according  to  the  theory 
adopted  in  the  preceding  paragraphs,  lies  in  the  greater  venosity  of 
the  blood,  that  is,  the  increased  tension  of  the  carbon  dioxid  follow- 
ing interruption  of  the  placental  circulation.  During  the  intra- 
uterine  period  it  is  evident  that  the  fetal  blood  is  aerated  so  well 
by  exchange  with  the  maternal  blood  that  it  does  not  act  as  a 
stimulus  to  the  fetal  respiratory  center.  The  fetus  is,  physiolog- 
ically speaking,  in  a  condition  of  apnea.  Since  the  maternal  blood 
acts  upon  the  respiratory  center  of  the  mother,  while  the  fetal 
blood  which  exchanges  gases  with  it  does  not  act  on  its  own  respira- 
tory center,  it  follows  that  the  fetal  respiratory  center  possesses  a 
lower  degree  of  irritability  than  that  of  the  mother,  and  we  may 
assume  that  this  condition  is  due,  in  part  at  least,  to  the  absence 
of  somatic  and  cutaneous  stimuli  in  the  protected  fetus. 

Dyspnea,  Hyperpnea,  Apnea. — By  the  term  dyspnea  in  its 
widest  sense  we  mean  any  noticeable  increase  in  the  force  or  rate  of 
the  respiratory  movements.  As  said  above,  such  a  condition  may 
be  caused  either  by  stimulation  of  sensory  nerves,  particularly 
the  pain  nerves,  or  by  an  increased  venosity  of  the  blood — that 
is,  by  an  increase  in  the  CO2  or  by  a  marked  decrease  in  the  oxygen. 
Changes  of  other  kinds  in  the  composition  of  the  blood,  some  of 
which  are  considered  in  the  next  chapter,  may  also  stimulate  the 
respiratory  center  and  cause  dyspnea.  The  dyspneic  movements 
naturally  show  many  degrees  of  intensity  corresponding  with  the 
strength  of  the  stimulus,  and  sometimes  the  initial  stages  are 
designated  as  hyperpnea,  while  the  term  dyspnea  is  reserved  for 
the  more  labored  breathing  in  which  the  expirations  are  active 
and  forced.  When  dyspnea  is  produced  by  withholding  air 

*  Cohnstein  and  Zuntz,  "Arch.  f.  die  gesammte  Physiol.,"  42,  342,  1888. 


INNERVATION    OF    THE    RESPIRATORY    MOVEMENTS.  707 

(suffocation)  the  respiratory  movements  become  more  and  more 
violent  until  they  take  on  a  convulsive  character.  This  stage 
is  succeeded  by  one  of  apparent  calm,  indicative  of  exhaustion  of 
the  centers.  Deep,  long-drawn  inspirations  follow  at  intervals 
and  finally  cease.  The  animal  lies  quietly,  with  feeble  heart  beat 
and  dilated  pupils,  in  a  condition  designated  as  asphyxia  or  com- 
plete asphyxia. 

The  term  apnea  means  literally  a  condition  of  no  breathing,  and 
since  this  condition  may  occur  from  several  causes  some  confusion  in 
nomenclature  has  resulted.  In  medical  literature  the  term  is  some- 
times employed  as  a  synonym  for  asphyxia  or  suffocation.  In 
physiological  literature  it  is  restricted  to  a  very  interesting  con- 
dition which  is  of  great  importance  with  reference  to  the  theories 
of  respiration.  This  condition  is  one  of  cessation  of  breathing 
movements  due  to  lack  of  stimulation  of  the  respiratory  center. 
It  is  brought  about  by  rapid  and  prolonged  ventilation  of  the 
lungs.  If,  for  instance,  in  a  rabbit  or  other  animal,  a  tracheal 
cannuia  is  inserted  and  connected  with  a  bellows  or  respiration 
apparatus,  the  lungs  may  be  inflated  artificially  at  a  rapid  rate 
for  any  given  period  of  time.  If  such  an  experiment  is  per- 
formed it  will  be  found  that  when  the  blasts  are  stopped  the 
animal  makes  no  breathing  movements  at  all,  sometimes  for  a  con- 
siderable interval.  When  the  respirations  start  again  they  begin 
with  feeble  movements,  which  gradually  increase  to  the  normal  am- 
plitude (Fig.  281).  One  may  produce  a  similar  condition  upon  him- 
self, approximately  at  least,  by  a  series  of  rapid,  forced  inspirations. 
The  question  of  importance  is:  Why  does  the  respiratory  center 
cease  to  act?  The  numerous  researches  made  upon  this  condition 
seem  to  show  very  clearly  that  in  the  ordinary  method  used  to  pro- 
duce it  two  factors  co-operate,  namely,  a  change  in  the  condition  of 
the  gases  of  the  blood  and  a  stimulation  of  sensory  fibers  in  the 
lungs,  the  latter  factor  bringing  about  a  reflex  inhibition  of  the 
respiratory  center.  Since  either  one  of  these  factors  alone  may 
cause  a  cessation  of  breathing,  some  authors  have  distinguished 
two  kinds  of  apnea,  apnea  vera  or  chemical  apnea,  and  apnea  vagi 
or  inhibitory  apnea.  1 1  is  generally  stated*  that  after  section  of  the 
vagi  it  is  more  difficult  than  in  the  normal  animal  to  produce  apnea 
by  vigorous  artificial  respiration,  so  doubtless  in  this  last  proce- 
dure, as  usually  carried  out  with  a  bellows,  the  rapid  stimulation 
of  the  inhibitory  fibers  of  the  vagus  by  the  expansion  of  the  lungs 
facilitates  the  production  of  a  true  or  chemical  apnea.  In  the  pre- 
ceding paragraphs  evidence  has  been  given  to  show  that  the  normal 
stimulus  to  the  center  is  due  to  the  presence  of  CO2,  and  it  fol- 
lows logically  that  the  more  complete  removal  of  this  gas  by  venti- 

*  See  Head,  "Journal  of  Physiology,"  10,  1,  and  279,  1889. 


708  PHYSIOLOGY    OF    RESPIRATION. 

lation  of  the  lungs  should  be  considered  as  the  chief  cause  of  true 
apnea.  Experimentally,  this  view  is  well  borne  out  by  an  old 
observation  of  Berns,  according  to  which  a  condition  of  apnea 


Fig.  281.— To  show  the  recovery  from  apnea.  The  animal  (rabbit)  had  been  venti- 
lated with  a  bellows  and  thrown  into  a  condition  of  apnea  shown  at  the  beginning 
of  the  record.  The  respirations  returned  first  as  feeble  movements  which  gradually  in- 
creased to  the  normal.— (Dawaan.) 

in  a  rabbit  may  be  cut  short  at  any  moment  by  a  blast  of  CO2 
sent  into  the  lungs,  a  blast  of  air  having  no  such  effect.  This 
observation  is  further  supported  by  experiments  by  Mosso  *  upon 
men,  in  which  he  shows  that  apnea  cannot  be  produced  by  inflation 
with  carbon  dioxid.  This  author  designates  the  condition  of 
diminished  C02  in  the  blood  as  acapnia.  According  to  this 
terminology,  true  apnea  is  duetto  a  condition  of  acapnia. 

Increased  rapidity  or  depth  of  breathing  tends  to  reduce  the 
concentration  of  C02  in  the  alveolar  air  and,  consequently,  the 
pressure  of  C02  in  the  arterial  blood.  When  this  pressure  falls  be- 
low a  certain  level  in  the  normal  animal  (19  to  24  mms.,  Zuntz),  the 
respiratory  center  is  not  stimulated.  There  is  a  condition  of  com- 
plete apnea.  Smaller  reductions  in  carbon  dioxid  pressure  cause 
partial  apnea,  that  is,  a  reduction  in  the  rate  or  amplitude  of  the 
respirations.  Voluntary  forced  respirations  in  man  maintained  for 
some  minutes  will  produce  a  similar  condition.  According  to  the 
interesting  account  given  by  Haldane  and  Poultonf  an  apnea  may 
be  produced  in  this  way  which  will  last  for  100  to  150  seconds,  and 
before  the  individual  begins  to  breathe  again  he  may  become 
very  blue  in  the  face,  owing  to  the  using  up  of  the  oxygen  in  the 
lungs.  In  addition  to  the  factors  discussed  above,  namely,  reflex 

*  Mosso,  "Archives  italiennes  de  biologie,"  40,  1,  1903. 

t  Haldane  and  Poulton,  "Journal  of  Physiology,"  37,  390,  1908. 


INNERVATION    OF    THE    RESPIRATORY    MOVEMENTS.  709 

inhibition  or  excitation  through  sensory  nerve  fibers  and  variations 
in  the  carbon  dioxid  of  the  blood,  it  is  to  be  borne  in  mind  that  this 
irritable  center  may  be  influenced  in  many  other  ways,  for  example, 
by  the  specific  action  of  various  drugs  or  toxins,  by  variations  in  the 
inorganic  elements  of  the  blood,  etc. 

Innervation  of  the  Bronchial  Musculature. — Numerous  in- 
vestigators, using  different  methods,  have  demonstrated  that  the 
bronchial  musculature  is  supplied  through  the  vagus  with  motor  and 
inhibitory  fibers,  bronchoconstrictor  and  bronchodilator  fibers,  as 
they  are  usually  called.*  Stimulation  of  the  constrictors  causes  a 
narrowing  of  the  bronchi,  and  therefore  increases  the  resistance  to 
the  inflow  and  outflow  of  air.  Some  observers  state  that  these  fibers 
are  normally  in  a  condition  of  tonic  activity  (Roy  and  Brown),  but 
others  find  little  evidence  for  this  belief.  An  artificial  tonus — 
that  is,  a  condition  of  maintained  activity  of  the  constrictor  fibers- 
may  be  set  up  by  the  action  of  those  drugs  (muscarin,  pilocarpin, 
etc.),  which  are  known  to  stimulate  the  endings  of  bulbar  auto- 
nomic  nerve-fibers.  Their  effect  is  removed  by  the  action  of  atro- 
pin.  These  fibers  are  stimulated  also  during  the  excitatory  stages 
of  asphyxia.  Reflex  stimulation  of  the  constrictors  is  obtained 
most  readily  (Dixon  and  Brodie)  by  irritation  of  the  nasal  mucous 
membrane,  and  it  seems  probable  that  in  bronchial  or  spasmodic 
asthma  these  fibers  are  also  stimulated  reflexly. 

The  normal  conditions  under  which  the  constrictors  and  dilators 
are  brought  into  play  can  scarcely  be  stated.  Irritating  vapors  or 
even  C02  lead  to  a  bronchoconstriction,  and  this  reflex,  as  stated  on 
p.  699,  may  be  regarded  as  protective.  When  a  constriction  of  the 
bronchial  musculature  exists  it  may  be  abolished  by  the  paralyzing 
action  of  atropin,  or  temporarily  by  injections  of  extracts  of 
lobelia,  or  by  the  anesthetic  effect  of  inhalations  of  chloroform  or 
ether.  Nicotin  also  causes  a  dilatation. 

*  For  references  to  literature,  see  Dixon  and  Brodie,  "Journal  of  Physi- 
ology/' 29,  97,  1903., 


CHAPTER  XXXVIII. 

THE  INFLUENCE  OF  VARIOUS  CONDITIONS  UPON 
THE  RESPIRATIONS. 

The  Effect  of  Muscular  Work  upon  the  Respiratory  Move- 
ments.— It  is  a  matter  of  common  experience  that  muscular  ex- 
ercise increases  the  rate  and  amplitude  of  the  respiratory  move- 
ments. The  increase  is  proportional  to  the  amount  of  muscular 
work,  so  that  although  there  is  a  very  large  additional  quantity  of 
CO2  given  off  to  the  blood  in  a  unit  of  time,  this  increase  is  elimi- 
nated so  completely  through  the  better  ventilation  of  the  lungs  that 
only  a  very  small  rise  takes  place  in  the  concentration  of  C02  in  the 
alveolar  air.  The  increased  respirations  not  only  provide  for  the 
removal  of  the  excess  of  carbon  dioxid  but  also  for  the  added  quan- 
tity of  oxygen  needed  by  the  working  muscles.  It  is  evident  that 
there  is  a  delicate  adjustment  between  muscular  activity  and 
respiratory  rate  and  the  nature  of  the  physiological  mechanism 
involved  has  given  rise  to  much  speculation  and  investigation. 
From  the  facts  presented  in  the  previous  chapter  it  would  seem 
probable  that  the  regulation  or  adaptation  is  effected  mainly 
through  the  increase  in  C02  .pressure  in  the  blood.  Some  older 
experiments  in  which  the  arterial  blood  was  examined  before  and 
during  exercise  show  that  there  was  no  constant  increase  in  its 
content  in  CO2  as  a  result  of  the  exercise;*  but  later  work  indicates 
that  this  is  evidence  rather  of  the  delicacy  and  completeness  of  the 
adaptation,  for  analyses  of  the  alveolar  air  show  that  the  concen- 
tration in  CO2  does  increase  with  muscular  work,  and  that  a  very 
small  rise  indeed  in  the  concentration  goes  along  with  a  large  aug- 
mentation in  the  respiration.  An  increase,  for  example,  from  5.6 
per  cent,  to  6  per  cent,  is  accompanied  by  an  increase  of  200  per 
cent,  in  the  breathing  (Haldane).  There  is  some  reason  to  believe 
that  in  the  beginning  of  muscular  work  the  respiratory  center  may 
be  stimulated  also  by  an  associated  activity  of  the  nerve  centers. 
The  nerve  impulses  coming  down  from  the  brain  along  the  voluntary 
nerve  tracts  may  overflow  into  the  respiratory  center  by  collateral 
branches  and  stimulate  the  center  or  increase  its  irritability  toward 
the  action  of  the  intrinsic  stimulus  of  the  carbon  dioxid.  An  associ- 
ated activity  of  this  character  is  called  upon  to  explain  the  increased 
*  Geppert  and  Zuntz,  "Pfliiger's  Archiv,"  42,  189,  1888. 
710 


INFLUENCE    OF    VARIOUS    CONDITIONS    ON   RESPIRATION.     711 

heart-rate  that  accompanies  even  slight  muscular  activity,  and  it 
seems  probable  that  a  similar  effect  is  exercised  upon  the  respira- 
tory center.*  When  muscular  activity  is  maintained  for  some 
time  the  lactic  acid  formed  in  the  muscle  escapes  to  some  extent  in 
the  blood  f  and  tends  to  lower  its  alkalinity.  This  factor  also 
should  augment  the  activity  of  the  respiratory  center.  In  long- 
continued  muscular  exercise,  in  fact,  the  fixed  acid  thus  added  to 
the  blood  may  be  sufficient  to  cause  a  lowering  of  CO2  pressure  as 
indicated  by  a  fall  in  the  concentration  of  CO2  in  the  alveolar  air. 

The  Effect  of  Variations  in  the  Composition  of  the  Air 
Breathed. — Variations  in  the  amount  of  nitrogen  in  the  inspired 
air  have  no  distinct  physiological  effect.  The  important  elements 
to  consider  are  the  oxygen  and  the  carbon  dioxid. 

Increased  Percentages  of  Oxygen. — The  normal  pressure  of  oxygen 
in  the  air  is  20  per  cent,  or  152  mms.  We  may  increase  this  pres- 
sure either  by  changing  the  volume  per  cent,  of  the  gas  or  by  raising 
the  barometric  pressure  by  compression.  The  somewhat  natural 
supposition  that  breathing  pure  oxygen — that  is,  oxygen  at  a  pres- 
sure of  760  mm. — should  have  a  beneficial  effect  on  the  oxidations 
of  the  body  has  found  no  support  in  physiological  experiments. 
Atmospheric  air  supplies  us  with  an  excess  of  oxygen  over  the  needs 
of  the  body;  a  still  further  increase  of  this  excess  has  no  positive 
advantage.  This  is  true  at  least  for  ordinary  conditions  of  rest  or 
moderate  activity.  In  excessive  and  prolonged  muscular  exertion 
the  supply  may  be  inadequate,  and  under  these  or  similar  condi- 
tions an  increase  in  the  percentage  of  oxygen  in  the  respired  air 
would  naturally  be  advantageous.  Paul  Bert,  in  his  interesting 
work  on  barometric  pressures,  J  has  called  attention  to  the  fact  that 
at  a  certain  pressure  oxygen  is  not  only  not  beneficial,  but,  on  the 
contrary,  is  markedly  toxic.  From  experiments  made  upon  a  great 
variety  of  animals  and  plants  he  concluded  that  all  living  things  are 
killed  when  the  oxygen  pressure  is  sufficiently  high, — say,  300  to  400 
per  cent.  Warm-blooded  animals  die  with  convulsions  when  sub- 
mitted to  3  atmospheres  of  pure  oxygen  or  15  atmospheres  of  air. 
At  these  high  pressures  the  blood  contains  about  28  volumes  of  oxy- 
gen to  each  100  c.c.  of  blood  instead  of  the  usual  20  volumes.  The 
additional  8  volumes  are  contained  in  solution.  Fish  also  are  killed 
when  the  oxygen  pressure  is  increased  to  such  a  point  that  the  water 
contains  10  volumes  of  dissolved  oxygen  to  each  100  c.c.  In  more 
recent  experiments  by  Smith ,§  made  upon  mice,  it  was  found  that 
oxygen  at  pressures  of  100  per  cent,  to  130  per  cent,  proves  fatal 

*  Krogh  and  Lindhard,  "Journal  of  Physiology,"  47,  112,  1914. 

t  Ryffel,  "Journal  of  Physiology,"  39,  1909. 

I  "La  pression  barometrique,"  p.  764,  Paris,  1878. 

§"  Journal  of  Physiology,"  24,  19,  1899. 


712  PHYSIOLOGY    OF    RESPIRATION. 

in  a  few  days,  the  animals  showing  inflammatory  changes  in  the 
lungs.  Oxygen  at  180  per  cent,  kills  mice  and  birds  within  twenty- 
four  hours.  Pressures  of  two  atmospheres  of  air  (40  per  cent.  O) 
have  no  injurious  effect.  No  adequate  chemical  explanation  can 
be  offered  at  present  for  this  toxic  action  of  oxygen  at  high  tensions. 
The  matter  is  one  of  practical  importance  in  connection  with  caisson 
and  submarine  work  and  the  therapeutical  use  of  oxygen. 

Decreased  Percentages  of  Oxygen. — Numerous  observers  (Bert, 
Zuntz,  et  al.)  have  shown  that  a  fall  in  oxygen  pressure  has  no 
perceptibly  injurious  result  until  it  reaches  about  10  per  cent.  At 
or  somewhat  below  this  pressure  the  hemoglobin  is  unable  to  take 
up  its  full  amount  of  oxygen,  and  the  body  consequently  suffers 
from  a  real  deficiency  in  its  oxygen  supply,  a  condition  designated 
as  anoxemia.  According  to  Bert's  experimental  results,  death  with 
convulsions  quickly  follows  a  fall  of  atmospheric  pressure  to  250 
mms.  (oxygen  pressure,  50  mms.  or  6  to  7  per  cent.).  Animals 
supplied  with  an  atmosphere  containing  a  deficient  amount  of 
oxygen  show  dyspneic  respirations  when  the  deprivation  of  oxygen 
is  made  with  some  suddenness.  When  the  oxygen  is  decreased 
slowly,  as  in  the  case  of  a  person  rebreathing  a  confined  portion  of 
air,  and  with  provision  made  to  absorb  the  CO2  as  it  is  expired, 
it  is  said  that  the  individual  experiences  so  little  discomfort  that  he 
may  voluntarily  continue  the  respirations,  in  spite  of  a  noticeable 
cyanosis,  until  he  falls  unconscious.  It  would  seem  that  the  nor- 
mal supply  of  oxygen,  20  per  cent.,  offers  a  large  factor  of  safety 
and  makes  provision  for  the  great  increase  in  oxygen  which  is  nec- 
essary during  muscular  activity.  When  the  supply  of  oxygen  is 
reduced  to  about  10  per  cent,  this  factor  of  safety  is  removed.  The 
individual  may  suffer  no  inconvenience  while  resting,  but  active 
muscular  exercise  may  produce  at  once  respiratory  discomfort  and 
labored  breathing. 

Increased  Percentages  of  Carbon  Dioxid. — It  was  pointed  out 
by  the  researches  of  Friedlander  and  Herter*  and  later  observers 
that  death  from  increased  percentages  of  C02  is  accompanied  by 
symptoms  quite  different  from  those  due  to  lack  of  oxygen.  As  the 
CO2  is  increased  a  noticeable  hyperpnea  may  be  observed  (Zuntz)  at 
a  concentration  of  about  2  per  cent.  When  the  concentration  of 
CC>2  reaches  8  per  cent,  to  10  or  15  per  cent,  there  is  distinct  dysp- 
nea; but  beyond  this  point  further  concentration,  instead  of  aug- 
menting the  respirations,  decreases  them,  and  the  animal  dies,  at 
concentrations  of  40  to  50  per  cent.,  without  convulsions,  but  with 
the  appearance,  rather,  of  a  fatal  narcosis.  It  is  probable  that  in 
these  concentrations  the  C02  exercises  a  direct  toxic  action  on  the 
nerve  cells. 

*  Friedlander  and  Herter,  "Zeitschrift  f.  physiol.  Chemie,"  2,  99,  1878, 
and  3,  19,  1879;  Haldane,  loc.  tit. 


INFLUENCE    OF    VARIOUS    CONDITIONS    ON    RESPIRATION.     713 

High  and  Low  Barometric  Pressures,  Mountain  Sickness, 
Caisson  Disease,  etc. — High  barometric  pressures  are  used  in 
submarine  work,  diving,  caisson  work,  etc.  As  stated  above,  it 
follows  from  the  work  of  Bert  and  Smith  that  when  the  pressure 
reaches  5  to  6  atmospheres  long  continuance  in  it  may  be  followed 
by  injurious  or  fatal  results  due  to  the  toxic  action  of  the  oxygen. 
If  the  pressure  is  increased  to  15  atmospheres  the  toxic  influence 
of  the  oxygen  brings  on  death  with  convulsions.  Practically, 
however,  such  pressures  are  not  encountered  in  submarine  work. 
A  caisson  is  a  wooden  or  steel  chamber  arranged  so  that  it  may 
be  sunk  under  water.  The  water  is  driven  out  by  air  under  pres- 
sure. Since  the  pressure  increases  1  atmosphere  for  each  10 
meters  (33  feet),  it  will  be  seen  that  very  high  pressures  of  air 
are  not  usually  required.  Caisson  workers  are  at  times  attacked 
by  serious  or  even  fatal  symptoms,  not  while  hi  the  compressed* 
air,  but  during  or  after  the  "  decompression"  that  is  necessary  in 
the  return  to  normal  conditions.  The  symptoms  consist  of  pains 
in  the  muscles  and  joints,  paralysis,  dyspnea,  congestion.  Those 
who  have  investigated  the  subject*  state  that  the  injurious  results 
are  due  to  a  too  rapid  decompression.  When  this  occurs  the  gases 
in  the  blood,  particularly  the  nitrogen,  are  suddenly  liberated  as 
bubbles,  which  block  the  capillaries  and  thus  produce  anemia  in 
different  organs.  If  the  decompression  is  effected  gradually  no  evil 
results  follow. 

The  effect  of  low  barometric  pressures  is  chiefly  of  interest  in 
connection  with  residence  in  high  altitudes,  balloon  ascensions, 
etc.  At  certain  altitudes,  from  3000  to  4000  meters,  disagreeable 
symptoms  are  experienced  by  many  persons,  especially  after 
muscular  effort,  which  are  designated  usually  under  the  term 
mountain  sickness.  The  individual  so  affected  suffers  from  head- 
ache, nausea,  vertigo,  great  weakness,  etc.  Much  investigation, 
especially  of  recent  years,  has  been  devoted  to  this  subject.f  Paul 
Bert  concluded,  from  his  numerous  experiments,  that  a  fall  in  baro- 
metric pressure  acts  upon  the  organism  only  in  so  far  as  there  is  a 
diminution  of  the  partial  pressure  of  the  oxygen  in  the  air  respired. 
This  view  has  been  generally  accepted  in  physiology,  and  mountain 
sickness  and  similar  disturbances  in  balloon  ascents  have  been 
explained,  therefore,  as  due  mainly  to  the  lack  of  oxygen, — that  is, 
to  the  condition  of  anoxemia.  Mosso,  on  the  contrary,  has  insisted 
upon  the  part  played  by  the  carbon  dioxid.  He  gives  experi- 

*  See  Bert,  loc.  cit.,  p.  939;  also  Hill  and  MacLeod,  "Journal  of  Physi- 
ology," 29,  382,  and  "Journal  of  Hygiene,"  3,  407. 

t  See  "Zunts  et  al.  Hohenklima  u.  Bergwanderungen  in  ihrer  Wirkung 
auf  d.  Menschen,"  Berlin,  1906.  Mosso  and  Morro,  "Archives  italiennes  de 
biologie,"  39,  387,  also  vols.  40  and  41.  Douglas  et  al,  "Physiological  Observa- 
tions made  on  Pike's  Peak,"  etc.;  "Philosophical  Trans.,"  London,  B.  203, 
185,  1913. 


714  PHYSIOLOGY    OF    RESPIRATION. 

ments  to  show  that  there  is  a  diminution  in  the  carbon  dioxid 
contents  of  the  blood  (a  condition  of  acapnia),  and  it  is  to  this, 
rather  than  to  the  anoxemia,  that  he  would  attribute  the  physio- 
logical results  of  low  barometric  pressures.  Other  authors  lay 
stress  upon  the  mechanical  disturbances  of  the  lung  circulation, 
while  still  others  assume  that  certain  vaguely  understood  cosmical 
influences — such  as  the  electrical  condition  of  the  air,  its  ioniza- 
tion,  or  radiations  of  some  kind — may  affect  the  metabolisms  of 
the  body.  The  balance  of  evidence,  however,  indicates  that  the 
chief  factor  in  the  production  of  mountain  sickness  is  deficiency 
in  oxygen,  particularly  when  the  oxygen  need  of  the  body  is  in- 
creased, as,  for  example,  in  muscular  exercise.  Experiments  seem 
to  show  that  the  total  amount  of  oxygen  in  the  arterial  blood  may 
not  be  diminished,  owing  to  the  greater  percentage  of  hemoglobin, 
but  the  hemoglobin  is  less  saturated,  and  the  oxygen  is  under  a 
lower  pressure  and,  therefore,  it  is  not  supplied  so  rapidly  to  the 
tissues.  At  very  high  altitudes  the  supply  of  oxygen  for  the  body 
exhibits  only  a  small  margin  of  safety,  and  we  may  suppose  that 
relatively  little  muscular  exercise,  with  its  attendant  increase  in 
oxygen  consumption,  will  suffice  to  deplete  the  supply  to  such  an 
extent  as  to  affect  the  brain  centers*  The  historical  incident 
of  the  death  of  Sivel  and  Croce"-Spinelli  at  an  altitude  of  8600 
meters  (barometric  pressure,  262  mms.;  oxygen  pressure,  52.4  mms.) 
gives  an  impressive  instance  of  the  physiological  effects  of  extreme 
altitudes. 

The  incidents  connected  with  the  ascent  in  the  balloon  Zenith  of  Sivel, 
Croce-Spinelli,  and  Tissandier,  April  15,  1875,  are  described  in  detail  by  the 
last  named  in  "La  Nature,"  1875,  p.  337,  also  in  Bert's  "La  pression  baro- 
metrique,"  p.  1061.  Only  Tissandier  survived.  The  balloonists  were  pro- 
vided with  bags  containing  oxygen  (72  percent.),  but  they  were  unable  to 
make  satisfactory  use  of  them  since  shortly  after  passing  7500  meters  they  be- 
came so  weak  that  the  effort  to  raise  the  arm  to  seize  the  oxygen  tube  was 
impossible.  Tissandier's  graphic  description  relates  that  at  8000  meters 
it  was  impossible  for  him  to  speak,  and  that  shortly  afterward  he  became 
entirely  unconscious.  None  of  the  three  seems  to  have  shown  any  signs  of 
violent  dyspnea.  It  is  noteworthy,  however,  that  the  heart-beats  were  very 
rapid,  and  that  they  experienced  at  first  great  depression  of  muscular  strength 
without  loss  of  consciousness.  The  onset  of  complete  unconsciousness  was 
sudden,  but  was  preceded  by  feelings  of  sleepiness,  which,  however,  were  not 
associated  with  any  distress. 

The  Respiratory  Quotient  and  its  Variations. — In  studying 
the  gaseous  exchanges  of  respiration  one  may  determine  the  varia- 
tions in  the  oxygen  absorbed  under  different  conditions  or  in  the 

carbon  dioxid  eliminated,  or  finally  in  the  ratio  of  one  to  the  other, 

c*o 

-Q-*,  which  is  known  as  the  respiratory  quotient.     In  short-lasting 

experiments  the  respiratory  quotient  is  not  a  very  reliable  indicator 


INFLUENCE   OF  VARIOUS   CONDITIONS   ON   RESPIRATION.      715 

of  the  extent  or  character  of  the  physiological  oxidations  in  the  body, 
since  any  alteration  in  the  depth  or  rapidity  of  the  respiratory 
movements  may,  by  changing  the  ventilation  of  the  alveoli,  make 
a  difference  in  the  output  of  CO2, — a  difference,  however,  which 
would  have  no  significance  in  regard  to  the  nutritive  changes  of  the 
body.  In  longer  experiments  and  in  those  during  which  the  respira- 
tory movements  are  not  altered  the  determination  of  this  ratio 
throws  light  upon  the  nature  of  the  material  that  is  undergoing 
oxidation  in  the  body,  as  will  be  apparent  from  the  following 
considerations:  Under  ordinary  conditions  of  rest  and  upon  a 
mixed  diet  the  R.  Q.  varies  between  0.65  and  0.95  (Loewy)  or 
between  0.75  and  0.89  (Magnus  Levy).  If,  however,  the  material 
oxidized  in  the  body  is  entirely  carbohydrate,  the  R.  Q.  should  be 

f^(~\ 

equal  to  unity:  -Q-2  =  1.  All  the  oxygen  used  in  the  combustion 
might  be  considered  as  uniting  with  the  C  to  form  CC>2,  since 
enough  O  is  present  in  the  sugar  to  account  for  that  used  in  oxidiz- 
ing the  H  to  H^O.  Or,  as  expressed  in  a  reaction, 

Dextrose. 

CeH12O2  +  6O2  =  6CO2  +  6H2O.     R.  Q.  =  f  =  1. 

The  number  of  molecules  of  CO2  formed  in  the  oxidation  is  equal 
to  the  number  of  molecules  of  O2  used.  If  fats  alone  are  oxidized 
in  the  body  the  R.  Q.  should  be  low  (0.7),  since  these  substances 
are  poor  in  oxygen  compared  with  the  amount  of  C  and  H  present 
in  the  molecule.  The  combustion  of  palmitin  may  be  represented 
as  follows : 

Palmitin,  C3H5(C16H31O2)3  =  C^H^A. 
2(CHHfle06)  +  14502  =  102C02  +  98H2O. 
R-  Q.  =  ttt  =  0.703. 

In  estimating  the  respiratory  quotient  for  proteins  one  must 
bear  in  mind  the  fact  that  these  substances  vary  somewhat  in 
composition  and,  moreover,  that  they  are  not  completely 
oxidized  in  the  body.  Calculations  based  upon  the  amount  of 
unoxidized  carbon  and  hydrogen  escaping  in  the  urine  and 
feces  give  the  average  figure  of  0.801  for  the  R.  Q.  of  proteins. 
It  is  evident  from  these  statements  that  an  increase  in  the 
proportion  of  carbohydrate  food  will  cause  the  R.  Q.  to  approach 
unity,  while  an  increase  in  protein  and  especially  in  fat  will 
lower  its  value.  In  this  way  we  can  understand  the  actual 
variation  observed  in  the  average  respiratory  quotient  of  different 
classes  of  animals,  as  shown  in  the  following  brief  table  (Loewy) : 

Horse,  herbivorous— R.Q.=  0.960 
Sheep,  "    =0.900 

Man,    omnivorous        "     =0.800 
Dog,    carnivorous        "    =0.750. 


716  PHYSIOLOGY    OF    RESPIRATION. 

In  starvation,  when  the  body  is  living  only  on  its  own  protein  and 
fat,  the  R.  Q.  is  lower  than  under  a  normal  diet,  falling  from  about 
0.8  to  0.7,  and  a  similar  drop  is  observed  in  diabetes,  since  in  this  con- 
dition also  the  body  is  burning  only  protein  and  fats.  By  a  deter- 
mination of  the  respiratory  quotient  before  and  after  varying  certain 
conditions  one  may  ascertain  whether  the  given  condition  causes 
a  change  in  the  character  of  the  body  metabolism.  For  example, 
Higgins  finds  that  alcohol  given  to  an  individual  may  cause  a  fall 
in  the  R.  Q.  in  a  few  minutes.  Since  alcohol  when  burnt  has  a  low 
coefficient,  0.667,  this  result  is  interpreted  to  mean  that  the  alcohol 
is  being  burnt  promptly  in  the  body.  In  nutritional  experiments 
the  R.  Q.  is  used  very  commonly  as  an  index  of  the  proportions  of 
fat  and  carbohydrate  that  are  being  consumed  in  the  body.  Under 
certain  exceptional  conditions  the  R.  Q.  may  rise  even  above  unity. 
In  convalescence,  for  instance,  after  a  wasting  disease  when  the 
individual  is  increasing  rapidly  in  weight  from  the  formation  of  new 
body  fat,  or  in  certain  animals,  geese,  in  which  fat  may  be  made  to 
form  readily  by  excessive  feeding  of  carbohydrates.  In  such  cases 
an  oxygen-rich  food  is  converted  to  an  oxygen-poor  one,  so  that 
some  of  the  oxygen  must  be  split  off  partly  as  carbon  dioxid,  and 
there  is  a  larger  output  of  this  substance  in  the  expired  air. 

Modified  Respiratory  Movements. — Laughing,  coughing,  yawn- 
ing, sneezing,  sobbing,  and  even  vomiting  may  be  considered 
as  modified  respiratory  movements,  since  the  same  group  of  muscles 
comes  into  play.  These  are  all  movements,  with  the  exception  of 
yawning,  which  may  be  regarded  as  reflexes  that  have  nothing  to 
do  directly  with  the  processes  of  respiration.  A  most  interesting 
variation  of  the  normal  type  of  respiration  is  known  as  the  Cheyne- 
Stokes  respiration.  It  occurs  in  certain  pathological  conditions, 
such  as  arteriosclerosis,  uremic  states,  fatty  degeneration  of  the 
heart,  and  especially  under  conditions  of  increased  intracranial 
pressure.  It  is  characterized  by  the  fact  that  the  respiratory 
movements  occur  in  groups  (10  to  30)  separated  by  apneic  pauses, 
which  may  last  for  a  number  (30  to  40)  of  seconds.  After  each  pause 
the  respirations  begin  with  a  small  movement,  gradually  increase 
to  a  maximum,  and  then  fall  off  gradually  to  the  point  of  complete 
cessation  (see  Fig.  282) .  Great  variations,  however,  are  shown  in 
the  character  and  number  of  the  respirations  during  the  so-called 
dyspneic  phase.  From  observations  made  by  means  of  the 
sphygmomanometer  Eyster*  has  shown  that  in  this  condition 
there  are  also  rhythmic  waves  of  blood-pressure  (Traube-Hering 
waves),  and  according  to  the  relation  of  these  pressure  waves  to 
the  groups  of  respirations  the  Cheyne-Stokes  cases  fall  into  two 
groups.  In  one  group  the  dyspneic  phase  coincides  with  a  fall 

*  Eyster,  Journal  of  Experimental  Medicine,"  1906. 


INFLUENCE    OF   VARIOUS    CONDITIONS    ON    RESPIRATION.     717 

of  blood-pressure  and  a  slowing  of  the  pulse-rate.  In  the  other 
group  the  reverse  relations  hold,  the  blood-pressure  and  pulse-rate 
both  rising  during  the  dyspneic  phase  and  falling  during  the  apnea. 
This  latter  group  consists  of  cases  in  which  there  is  evidence  of 


Fig.  282. — Record  showing  typical  Cheyne-Stokes  respiration  (from   a  case  of  aortic  and 
mitral  insufficiency  with  arteriosclerosis).       The  time  record  gives  seconds. 

increased  intracranial  tension.  Under  experimental  conditions 
the  author  was  able  to  show  on  dogs  that  an  artificial  increase  in 
intracranial  tension  calls  forth  Cheyne-Stokes  respirations,  whenever 
it  happens  that  rhythmic  changes  in  blood-pressure  are  produced 
of  such  a  character  that  the  blood-pressure  rises  and  falls  alternately 
above  and  below  the  line  of  intracranial  pressure.  It  is  probable, 
therefore,  that  in  the  clinical  cases  associated  with  a  rise  of  intra- 
cranial pressure  the  blood-pressure  likewise  rises  and  falls  above 
and  below  intracranial  tension,  and  that  the  alternating  periods 
of  apnea  and  dyspnea  are  due  to  this  fact  in  this  class  of  cases. 
When  the  blood-pressure  falls  below  intracranial  pressure  there 
is  a  condition  of  deep  anemia  of  the  medulla  sufficient  to  suspend 
the  activity  of  the  respiratory  center.  The  following  rise  of  blood- 
pressure  by  forcing  more  blood  through  the  medulla  calls  forth  a 
group  of  respiratory  movements. 

By  examination  of  the  expired  air  Pembrey*  has  shown 
that  during  the  dyspneic  phase  the  percentage  of  CO2  in  the 
alveolar  air  is  markedly  diminished  (2  per  cent.),  and  he  believes, 
therefore,  that  the  following  phase  of  apnea  is  due  entirely  to 
this  washing  out  of  the  CO2,  that  is,  to  the  removal  of  the  normal 
stimulus  to  the  respiratory  center.  Practically  he  finds  that 
the  apneic  phase  can  be  removed  by  the  administration  of 
either  pure  oxygen  or  carbon  dioxid  (2.2  to  11.2  per  cent.). 
Pembrey  does  not  give  the  clinical  histories  of  his  patients,  but 

*  Pembrey,  "Journal  of  Pathology  and  Bacteriology,"  12,  258,  1908. 


718  PHYSIOLOGY    OF    RESPIRATION. 

apparently  he  has  studied  cases  belonging  chiefly  to  Eyster's 
first  group.  None  of  the  suggestions  made  at  present  seem  to 
account  adequately  for  the  very  labored  breathing  at  the  acme 
of  the  dyspneic  phase,  and  the  phenomenon  evidently  requires 
further  experimental  study. 

More  or  less  rhythmical  variations  in  the  strength  of  the 
breathing  movements  have  been  described  also  in  normal  sleep, 
hibernation,  chloral  narcosis,  high  altitudes  etc.,  but  nothing  so 
definite  and  characteristic  as  in  these  very  interesting  Cheyne- 
Stokes  cases. 


SECTION  VII. 
PHYSIOLOGY  OF  DIGESTION  AND  SECRETION. 


CHAPTER  XXXIX. 
MOVEMENTS  OF  THE  ALIMENTARY  CANAL. 

Mastication. — Mastication  is  an  entirely  voluntary  act.  The 
articulation  of  the  mandibles  with  the  skull  permits  a  variety  of 
movements;  .the  jaw  may  be  raised  and  lowered,  may  be  projected 
and  retracted,  or  may  be  moved  from  side  to  side,  or  various  com- 
binations of  these  different  directions  of  movement  may  be  effected. 
The  muscles  concerned  in  these  movements  and  their  innervation 
are  described  as  follows:  The  masseter,  temporal,  and  internal 
ptery goids  raise  the  jaw;  these  muscles  are  innervated  through  the 
inferior  maxillary  division  of  the  trigeminal.  The  jaw  is  depressed 
mainly  by  the  action  of  the  digastric  muscle,  assisted  in  some  cases 
by  the  mylohyoid  and  the  geniohyoid.  The  two  former  receive 
motor  fibers  from  the  inferior  maxillary  division  of  the  fifth  cranial, 
the  last  from  a  branch  of  the  hypoglossal.  The  lateral  movements 
of  the  jaws  are  produced  by  the  external  pterygoids,  when  acting 
separately.  Simultaneous  contraction  of  these  muscles  on  both 
sides  causes  projection  of  the  lower  jaw.  In  this  latter  case  forcible 
retraction  of  the  jaw  is  produced  by  the  contraction  of  a  part  of  the 
temporal  muscle.  The  external  pterygoids  also  receive  their  motor 
fibers  from  the  fifth  cranial  nerve,  through  its  inferior  maxillary 
division.  The  grinding  movements  commonly  used  in  masticating 
the  food  between  the  molar  teeth  are  produced  by  a  combination  of 
the  action  of  the  external  pteryogids,  the  elevators,  and  perhaps 
the  depressors.  At  the  same  time  the  movements  of  the  tongue 
and  of  the  muscles  of  the  cheeks  and  lips  serve  to  keep  the  food 
properly  placed  for  the  action  of  the  teeth,  and  to  gather  it  into 
position  for  the  act  of  swallowing. 

Deglutition. — The  act  of  swallowing  is  a  complicated  reflex 
movement  which  may  be  initiated  voluntarily,  but  is,  for  the  most 
part,  completed  quite  independently  of  the  will.  The  classical 
description  of  the  act  given  by  Magendie  divides  it  into  three  stages, 

i719 


720  PHYSIOLOGY  OF  DIGESTION  AND  SECRETION. 

corresponding  to  the  three  anatomical  regions — mouth,  pharynx, 
and  esophagus — through  which  the  swallowed  morsel  passes  on  its 
way  to  the  stomach.  The  first  stage  consists  in  the  passage  of  the 
bolus  of  food  through  the  isthmus  of  the  fauces, — that  is,  the 
opening  lying  between  the  ridges  formed  by  the  palatoglossi  muscles, 
the  so-called  anterior  pillars  of  the  fauces.  This  part  of  the  act  is 
usually  ascribed  to  the  movements  of  the  tongue  itself.  The  bolus 
of  food  lying  upon  its  upper  surface  is  forced  backward  by  the  ele- 
vation of  the  tongue  against  the  soft  palate  from  the  tip  toward 
the  base.  This  portion  of  the  movement  may  be  regarded  as  vol- 
untary, to  the  extent  at  least  of  manipulating  the  food  into  its  proper 
position  on  the  dorsum  of  the  tongue,  although  it  is  open  to  doubt 
whether  the  entire  movement  is  usually  effected  by  a  voluntary 
act.  Under  normal  conditions  the  presence  of  moist  food  upon  the 
tongue  seems  essential  to  the  complete  execution  of  the  act ;  and  an 
attempt  to  make  the  movement  with  very  dry  material  upon  the 
tongue  is  either  not  successful  or  is  performed  with  difficulty.  The 
second  act  comprises  the  passage  of  the  bolus  from  the  isthmus  of 
the  fauces  to  the  esophagus, — that  is,  its  transit  through  the  pharynx. 
The  pharynx  being  a  common  passage  for  the  air  and  the  food,  it  is 
important  that  this  part  of  the  act  should  be  consummated  quickly. 
According  to  the  older  description,  the  motor  power  driving  the 
bolus  downward  through  the  pharynx  is  derived  from  the  contrac- 
tion of  the  pharyngeal  muscles,  particularly  the  constrictors,  which 
contract  from  above  downward  and  drive  the  food  into  the  esopha- 
gus. Kronecker  and  Meltzer,*  however,  have  shown  that  the  con- 
traction of  the  mylohyoid  muscle  in  the  floor  of  the  mouth  is  the 
most  important  factor  in  this  act  of  shooting  the  food  suddenly 
through  the  pharynx  into  the  esophagus.  The  contraction  of  this 
muscle  marks  the  beginning  of  the  purely  involuntary  part  of  the 
act  of  swallowing.  The  bolus  of  food  lies  upon  the  dorsum  of  the 
tongue  and  by  the  pressure  of  the  front  of  the  tongue  against  the 
hard  palate  it  is  shut  off  from  the  front  part  of  the  mouth  cavity. 
When  the  mylohyoids  contract  sharply  the  bolus  is  put  under  pres- 
sure and  is  shot  into  and  through  the  pharynx.  This  effect  is  aided 
by  the  contraction  of  the  hyoglossi  muscles,  which  by  moving  the 
tongue  backward  and  downward  tend  to  increase  the  pressure  put 
upon  the  food.  Simultaneously,  a  number  of  other  muscles  are 
brought  into  action,  the  general  effect  of  which  is  to  shut  off  the 
nasal  and  laryngeal  openings  and  thus  prevent  the  entrance  of 


MOVEMENTS  OF  THE  ALIMENTARY  CANAL.  721 

food  into  the  corresponding  cavities.     The  whole  reflex  is  there- 
fore an  excellent  example  of  a  finely  co-ordinated  movement. 

The  following  events  are  described:  The  mouth  cavity  is  shut 
off  by  the  position  of  the  tongue  against  the  palate  and  by  the  con- 
traction of  the  muscles  of  the  anterior  pillars  of  the  fauces.  The 
opening  into  the  nasal  cavity  is  closed  by  the  elevation  of  the  soft 
palate  (action  of  the  levator  palati  and  tensor  palati  muscles)  and 
the  contraction  of  the  posterior  pillars  of  the  fauces  (palatopharyn- 
geal  muscles)  and  the  elevation  of  the  uvula  (azygos  uvulae  muscle). 
The  soft  palate,  uvula,  and  posterior  pillars  thus  form  a  sloping 
surface  shutting  off  the  nasal  chamber  and  facilitating  the  passage  of 
the  food  backward  through  the  pharynx.  The  respiratory  opening 
into  the  larynx  is  closed  by  the  adduction  of  the  vocal  cords  (lateral 
crico-arytenoids  and  constrictors  of  the  glottis)  and  by  the  strong 
elevation  of  the  entire  larynx  and  a  depression  of  the  epiglottis  over 
the  larynx  (action  of  the  thyrohyoids,  digastrics,  geniohyoids,  and 
mylohyoids  and  the  muscles  in  the  arytenonepiglottidean  folds). 
If  the  elevation  of  the  larynx  be  prevented  by  fixation  of  the  thy- 
roid the  act  of  swallowing  becomes  impossible.  There  is  also  at 
this  time,  apparently  as  a  regular  part  of  the  swallowing  reflex, 
a  slight  inspiratory  movement  of  the  diaphragm,  the  so-called 
swallowing  respiration.  The  movements  of  the  epiglottis  during 
this  stage  of  swallowing  have  been  much  discussed.  The  usual 
view  is  that  it  is  pressed  down  upon  the  laryngeal  orifice  like  the  lid 
of  a  box  and  thus  effectually  protects  the  respiratory  passage.  It 
has  been  shown,  however,  that  removal  of  the  epiglottis  does  not 
prevent  normal  swallowing,  and  Stuart  and  McCormick*  have 
reported  the  case  of  a  man  in  whom  part  of  the  pharynx  had  been 
permanently  removed  by  surgical  operation  and  in  whom  the 
epiglottis  could  be  seen  during  the  act  of  swallowing.  In  this 
individual,  according  to  their  observations,  the  epiglottis  was  not 
folded  back  during  swallowing,  but  remained  erect.  Kanthack  and 
Anderson  t  state  that  in  normal  individuals  the  movement  of  the 
epiglottis  backward  during  swallowing  may  be  felt  by  simply  passing 
the  finger  back  into  the  pharynx  until  it  comes  into  contact  with  the 
epiglottis.  According  to  most  observers,  it  is  not  necessary  for 
the  protection  of  the  larynx  that  the  epiglottis  shall  be  actually 
folded  down  over  it  by  the  contraction  of  its  own  muscles.  The 
forcible  lifting  of  the  larynx,  together  with  the  descent  of  the  base 
of  the  tongue,  effects  the  same  result  by  mechanically  crowding  the 
parts  together,  and  the  larynx  is  still  further  guarded  by  the  ap- 
proximation of  the  false  and  true  vocal  cords,  thus  closing  the  glottis. 
The  whole  act  is  very  rapid  as  well  as  complex,  so  that  not  more 

*  "Journal    of   Anatomy   and    Physiology, "    1892. 
t  "Journal  of  Physiology,"  14,  154,  1893. 
46 


722  PHYSIOLOGY  OF  DIGESTION  AND  SECRETION. 

than  a  second  elapses  between  the  beginning  of  the  contraction  oi 
the  mylohyoids  and  the  entrance  of  the  food  into  the  upper  end  of 
the  esophagus. 

The  passage  of  the  food  through  the  esophagus  differs  apparently 
with  its  consistency.  When  the  food  is  liquid  or  very  soft  Kronecker 
and  Meltzer  have  shown  that  it  is  shot  through  the  whole  length  of 
the  esophagus  by  the  force  of  the  initial  act  of  swallowing.  It- 
arrives  at  the  lower  end  of  the  esophagus  in  about  0.1  sec.,  and  may 
pass  immediately  into  the  stomach  or  may  lie  some  moments  in  the 
esophagus  according  to  the  conditions  of  the  sphincter  guarding 
the  cardiac  orifice.  When,  however,  the  food  is  solid  or  semi- 
solid,  as  was  shown  by  Cannon  and  Moser,  it  is  forced  down  the 
esophagus  by  a  peristaltic  movement  of  the  musculature.  The 
circular  muscles  are  constricted  from  above  downward  by  an  ad- 
vancing muscular  wave.  The  upper  portion  of  the  esopha- 
gus contains  cross-striated  fibers  indicating  rapid  contraction; 
the  lower  end  consists  of  plain  muscle  only,  while  the  intermediate 
portion  is  a  mixture  of  the  two  varieties.  Kronecker  and  Meltzer 
believe  that  each  of  these  segments  contracts  as  a  whole  and  in 
orderly  succession,  but  other  observers,  on  the  evidence  furnished 
by  Roentgen-ray  photographs,  agree  that  there  is  no  perceptible 
pause  in  the  downward  movement  of  the  wave  of  contraction.  These 
same  movements  occur  in  the  swallowing  of  liquid  or  soft  food,  but 
in  such  cases  the  peristaltic  wave  follows  the  actual  descent  of  the 
food.  According  to  the  observation  of  Kronecker  and  Meltzer,  it 
takes  about  6  sec.  for  the  peristaltic  wave  to  reach  the  stomach, 
and  the  passage  of  the  food  through  the  cardia  takes  place  with 
sufficient  energy  to  give  rise  to  a  murmur  that  may  be  heard  by 
auscultating  over  this  region.  In  the  case  of  the  more  liquid  food 
that  is  shot  at  once  to  the  lower  end  of  the  esophagus,  it  may 
apparently  pass  at  once  into  the  stomach  or  it  may  lie  in  the 
esophagus  until  the  wave  of  contraction  reaches  it  (6  sec.)  and 
forces  it  through  the  opening.  According  to  the  observations 
made  by  Hertz,*  liquids  or  liquid  food  are  held  up  at  the  end 
of  the  esophagus  and  pass  slowly  into  the  stomach  through  the 
sphincter.  He  estimates  that  an  interval  of  from  4.6  to  8.6 
sec.  elapses  before  the  swallowed  bolus  disappears  into  the  stom- 
ach, about  one-half  of  this  time  being  occupied  by  the  pas- 
sage to  the  bottom  of  the  esophagus  and  one-half  in  the  tran- 
sit through  the  cardiac  orifice  of  the  stomach. 

Nervous  Control  of  Deglutition. — The  entire  act  of  swallowing, 

as  has  been  said,  is  essentially  a  reflex  act.    Even  the  comparatively 

simple  wave  of  contraction  that  sweeps  over  the  esophagus  is  due 

to  a  reflex  nervous  stimulation,  and  is  not  a  simple  conduction  of 

*  Hertz,  "Guy's  Hospital  Reports,"  61,  389,  1907. 


MOVEMENTS    OF    THE   ALIMENTARY    CANAL.  723 

contraction  from  one  portion  of  the  tube  to  another.  This  fact  was 
demonstrated  by  the  experiments  of  Mosso,*  who  found  that  after 
removal  of  an  entire  segment  from  the  esophagus  the  peristaltic 
wave  passed  in  due  time  to  the  portion  of  the  esophagus  left  on  the 
stomach  side,  in  spite  of  the  anatomical  break.  The  same  experi- 
ment was  performed  successfully  on  rabbits  by  Kronecker  and 
Meltzer.  Observation  of  the  stomach  end  of  the  esophagus  in  this 
animal  showed  that  it  went  into  contraction  two  seconds  after  the 
beginning  of  a  swallowing  act  whether  the  esophagus  was  intact  or 
ligated  or  completely  divided  by  a  transverse  incision.  A  still 
more  striking  proof  of  the  same  fact  is  the  interesting  case  cited 
by  v.  Mikulicz  of  a  man  in  whom  a  portion  of  the  esophagus 
had  been  resected  on  account  of  a  carcinoma.  The  lower  end 
of  the  esophagus  was  given  a  fistulous  opening  in  the  neck  and 
and  it  was  found  that  food  introduced  into  this  opening  was 
not  moved  toward  the  stomach  until  the  patient  made  a  swallow- 
ing movement.f  The  afferent  nerves  concerned  in  this  reflex 
are  the  sensory  fibers  to  the  mucous  membrane  of  the  pharynx 
and  esophagus,  including  branches  of  the  glossopharyngeal, 
trigeminal,  vagus,  and  superior  laryngeal  division  of  the  vagus. 
Artificial  stimulation  of  this  last  nerve  in  the  lower  animals 
is  known  to  produce  swallowing  movements.  Several  observers 
have  attempted  to  determine  the  precise  area  or  areas  in  the 
pharyngeal  membrane  from  which  the  sensory  impulses  lib- 
erating the  reflex  normally  start.  According  to  Kahn,J  the 
most  effective  areas  from  whose  stimulation  the  reflex  may  be 
produced  vary  in  location  in  different  animals.  In  the  rabbit  the 
reflex  is  originated  most  easily  by  stimulation  at  the  entrance  to 
the  pharynx — the  soft  palate — along  the  line  extending  from  the 
posterior  edge  of  the  hard  palate  to  the  tonsils  (superior  maxil- 
lary branch  of  trigeminal);  in  the  dog  irritation  of  the  posterior 
pharyngeal  wall  is  most  effective  (glossopharyngeal  nerve);  in 
monkeys  the  area  is  approximately  as  in  rabbits, — that  is,  in  the 
region  of  the  tonsils.  The  motor  fibers  concerned  in  the  reflex 
comprise  the  hypoglossal,  the  trigeminal,  the  glossopharyngeal, 
the  vagus,  and  the  spinal  accessory.  For  an  act  of  such  complexity 
and  such  perfect  co-ordination  it  has  been  assumed  that  there  is  a 
special  nerve  center,  the  swallowing  or  deglutition  center,  which  has 
been  located  in  the  medulla  at  the  level  of  the  origin  of  the  vagi. 
There  is  little  positive  knowledge,  however,  concerning  the  existence 
of  this  center  as  a  definite  group  of  intermediary  nerve  cells,  after 
the  type  of  the  vasoconstrictor  or  respiratory  center,  which  send 
their  axons  to  the  motor  nuclei  of  the  several  efferent  nerves  con- 

*  Moleschott's  "Untersuchungen,"  1876,  volume  xi. 

t  Quoted  from  Cohnheim  in  Nagel's  "Handbuch  d.  Physiologic.55 

j  Kami,  "Archiv  f.  Physiologic,"  1903,  suppl.  volume,  386. 


724  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

cerned.  As  in  the  case  of  other  complicated  reflex  acts,  we  can  only 
say  that  the  deglutition  reflex  is  controlled  by  a  definite  nervous 
mechanism  the  final  motor  cells  of  which  are  scattered  in  the  several 
motor  nuclei  of  the  efferent  nerves  mentioned  above. 

So  far  as  the  esophagus  is  concerned,  the  motor  fibers  are 
received  from  the  vagus,  and  in  normal  swallowing  these  fibers  are 
excited  reflexly  from  the  pharynx  at  the  beginning  of  the  act. 
That  is  to  say,  the  initial  sensory  stimulus  in  the  pharynx  liberates 
a  series  of  reflex  movements  which  begin  with  the  contraction  of  the 
mylohyoid  muscle  and  end  with  a  peristaltic  wave  that  progresses 
in  orderly  fashion  along  the  esophagus.  It  has  been  shown, 
however,  that  the  bolus  when  it  reaches  the  esophagus  may  start 
a  different  order  of  reflexes  by  local  stimulation  of  the  sensory  fibers. 
These  stimuli  lead  to  reflex  contraction  of  the  musculature  above 
the  bolus,  and  thus  a  series  of  reflexes  are  liberated  which  are  suffi- 
cient to  move  the  bolus  downward.  If  the  primary  reflex  initiated 
at  the  beginning  of  the  swallow  proves  inefficient,  that  is  to  say, 
if  it  succeeds  only  in  forcing  the  bolus  into  the  top  of  the  esophagus, 
it  may  be  assumed  that  this  secondary  or  accessory  mechanism 
comes  into  play  and  provides  for  the  transportation  of  the  bolus 
to  the  stomach.  In  this  series  of  secondary  reflexes,  as  in  the  more 
complicated  primary  reflex,  the  vagus  nerve  forms  a  part  of  the 
path  and  the  reflex  center  lies,  therefore,  in  the  medulla. 

Cardiac  Sphincter. — At  the  cardia  or  cardiac  orifice  the  cir- 
cular layer  of  muscle  acts  as  a  sphincter.  When  the  stomach  is 
empty  this  sphincter  is  probably  relaxed.  When  the  stomach 
contains  food  the  sphincter  is  thrown  into  tone,  and  thus  shuts  off 
the  gastric  cavity  from  the  esophagus.  The  sphincter  receives 
both  motor  and  inhibitory  fibers  from  the  vagus  and  inhibitory 
fibers  from  the  sympathetic  system  by  way  of  the  celiac  ganglion. 
In  addition  it  is  supplied  from  the  intrinsic  plexus,  plexus  of 
Auerbach,  which,  as  elsewhere  in  the  alimentary  canal,  seems  to 
be  capable  of  regulating  the  movements  of  the  musculature  inde- 
pendently of  the  extrinsic  nerves.  The  tonic  contraction  of  the 
sphincter  that  occurs  when  the  stomach  contains  food  is  main- 
tained, according  to  Cannon,*  by  a  reflex  through  this  intrinsic 
plexus,  the  stimulus  initiating  the  reflex  being  due  to  the  acid 
present  in  the  gastric  secretion.  The  peristaltic  wave  sweeping 
down  the  esophagus  is  preceded,  in  the  lower  part  of  the  esophagus 
at  least,  by  a  wave  of  inhibition  or  relaxation.  This  latter  phase 
affects  the  sphincter  and  the  adjacent  musculature  of  the  stomach 
and  clears  the  path  for  the  bolus,  so  that  the  following  wave  of 
contraction  may  squeeze  it  through  the  relaxed  orifice  without 
serious  resistance.  After  the  passage  of  the  bolus  into  the  stomach 
*  Cannon,  "The  Mechanical  Factors  of  Digestion,"  1911. 


MOVEMENTS    OF    THE    ALIMENTARY    CANAL.  725 

the  sphincter  again  falls  into  tone  until  another  peristaltic  wave 
approaches  from  the  esophageal  side. 

The  Anatomy  of  the  Stomach. — The  stomach  in  man  belongs 
to  the  simple  type  as  distinguished  from  the  compound  stomachs 
of  some  of  the  other  mammalia, — the  ruminating  animals,  for 
example.  Physiological  and  histological  investigations  have  shown, 
however,  that  the  so-called  simple  stomachs  are  divided  into  parts 
that  have  different  properties  and  functions.  The  names  and  bound- 
aries of  these  parts  can  not  be  stated  precisely,  since  they  vary  in 
different  animals,  and,  moreover,  there  is  some  want  of  agree- 
ment among  different  authors  regarding  the  nomenclature  of 
the  parts  of  the  stomach.*  For  the  purposes  of  a  physiological 
description  we  may  use  the  names  indicated  in  the  accompany- 
ing schematic  figure.  The  main  interest  lies  in  the  separation  of 
the  pyloric  part  of  the  stomach  or  antrum  pylori  from  the  main 
cavity  of  the  stomach.  The  line  of  separation  is  marked  by  a 
fissure  on  the  small  curvature,  incisura  angularis  (7.  A.),  and  on  the 
large  curvature  by  an  abrupt  change  of  direction.  The  pyloric  part 


Pyloricfoartcf&fomad 
or  antrum  pylori 


Position  of 
transverse 


Fundua 


'ntermectiote.  qr 
prefiylorie  reyion. 


Fig.  283. — Schematic  figure  to  show  the  different  parts  of  the  stomach. — (After  Reteiua.) 

makes  an  angle,  therefore,  with  the  body  of  the  stomach,  and  differs 
from  the  latter  in  its  musculature,  the  macroscopical  and  microscop- 
ical characteristics  of  its  mucous  membrane,  and  in  its  functional 
importance.  Some  writers  divide  the  antrum  further  into  a 
pyloric  vestibule,  forming  the  larger  part  of  the  antrum,  and  a 
pyloric  canal,  consisting  of  the  narrower  tube-like  portion  which 
connects  with  the  duodenum.  The  pyloric  canal  >s  short,  about 
3  cm.,  and  is  more  marked  as  a  separate  structure  in  the  stomach 
of  young  children.  The  rest  of  the  stomach  falls  into  two  sub- 
divisions, the  fundus  and  the  corpus  or  body.  The  fundus  is  the 
blind,  rounded  end  of  the  stomach  to  the  left  of  the  cardia,  or,  in 
a  vertical  position  of  the  stomach,  the  portion  that  lies  above  a 
horizontal  plane  passing  through  the  cardia;  the  portion  between 

*  See  His,  "Archiv  f.  Anatomic/'  1903,  p.  345;  also  Cunningham,  "Trans- 
actions of  the  Royal  Society  of  Edinburgh,"  45,  9,  1905-06. 


726  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

the  fundus  and  the  pylorus  is  the  body  of  the  stomach  or  the 
intermediate  or  prepyloric  region.  This  latter  region  shows  in 
many  animals  a  characteristic  structure  in  its  secreting  glands, 
and  it  is  in  this  portion  that  the  hydrochloric  acid  of  the  gastric 
juice  is  mainly  secreted. 

The  Musculature  of  the  Stomach. — The  musculature  of  the 
stomach  is  usually  divided  into  three  layers, — &  longitudinal,  an 
oblique,  and  a  circular  coat.  The  longitudinal  coat  is  continuous 
at  the  cardia  with  the  longitudinal  fibers  of  the  esophagus;  it  spreads 
out  from  this  point  along  the  length  of  the  stomach,  forming  a  layer 
of  varying  thickness;  along  the  curvatures  the  layer  is  stronger 
than  on  the  front  and  posterior  surfaces,  while  at  the  pyloric  end  it 
increases  considerably  in  thickness,  and  passes  over  the  pylorus  to 
be  continued  directly  into  the  longitudinal  coat  of  the  duodenum. 
The  layer  of  oblique  fibers  is  quite  incomplete;  it  seems  to  be 
continuous  with  the  circular  fibers  of  the  esophagus,  and  spreads 
out  from  the  cardia  for  a  certain  distance  over  the  front  and  posterior 
surfaces  of  the  fundus  of  the  stomach,  but  toward  the  pyloric  end 
disappears,  seeming  to  pass  into  the  circular  fibers.  The  circular 
coat,  which  is  placed  between  the  two  preceding  layers,  is  the  thick- 
est and  most  important  part  of  the  musculature  of  the  stomach. 
At  the  fundus  the  circular  bands  are  thin  and  somewhat  loosely 
placed,  but  toward  the  pyloric  end  they  increase  much  in  thickness, 
forming  a  strong,  muscular  mass,  which,  as  we  shall  see,  plays  the 
most  important  part  in  the  movements  of  the  stomach.  At  the 
pylorus  itself  a  special  development  of  this  layer  functions  as  a 
sphincter  pylori,  which  with  the  aid  of  a  circular  fold  of  the  mucous 
membrane  makes  it  possible  to  shut  off  the  duodenum  completely 
from  the  cavity  of  the  stomach.  The  line  of  separation  between 
the  antrum  pylori  and  the  body  of  the  stomach  is  made  by  a 
special  thickening  of  the  circular  fibers  which  forms  a  structure 
known  as  the  "transverse  band"  by  the  older  writers,*  and  de- 
scribed more  recently!  as  the  "sphincter  antri  pylorici."  Under 
certain  conditions,  such  as  vomiting,  stimulation  of  the  vagus, 
etc.,  this  sphincter  may  be  contracted  with  such  force  as  to  sep- 
arate the  antrum  entirely  from  the  fundic  end  of  the  stomach. 

The  Movements  of  the  Stomach. — The  solid  food  remains  in 
the  stomach  for  several  hours,  and  during  this  time  the  musculature 
contracts  in  such  a  way  that  the  thinner  portions  as  they  are  formed 
by  digestion  are  ejected  from  time  to  time  through  the  pylorus  into 
the  intestine.  Except  at  the  definite  intervals  when  the  pyloric 
sphincter  relaxes  the  food  is  entirely  shut  off  from  the  rest  of  the 
alimentary  canal  by  the  tonic  closure  of  the  sphincters  at  the  cardia 

*  See  Beaumont,  "Physiology  of  Digestion, "  second  edition,  1847,  p.  104 
f  Hofmeister  und  Schiitz,  "Archiv  f.  exper.  Pathologic  imd  Pharmakol- 
ogie,"  1886,  vol.  xx. 


MOVEMENTS    OF    THE    ALIMENTARY    CANAL.  727 

and  the  pylorus.  There  is  a  certain  orderliness  in  the  movements 
of  the  stomach,  and  especially  in  the  separation  and  ejection  of  the 
more  liquid  from  the  solid  parts,  which  shows  the  existence  of  a 
specially  adapted  mechanism.  These  movements  have  been  studied 
by  many  investigators,  making  use  of  various  experimental  meth- 
ods. The  first  noteworthy  contributions  to  this  subject  were 
those  made  in  this  country  by  Beaumont  in  his  famous  observations 
upon  Alexis  St.  Martin,  the  Canadian  voyageur,  who  had  a  per- 
manent fistulous  opening  in  his  stomach  as  the  result  of  a  gunshot 
wound.*  In  recent  years  the  subject  has  been  studied  with  great 
success  by  means  of  the  x-rays,  f  on  the  excised  stomach,  J  and  by 
means  of  tambours  or  sounds  introduced  into  the  stomach  to 
measure  the  pressure  changes.  §  These  researches  all  unite  in  em- 
phasizing one  fundamental  point — namely,  that  the  fundic  end 
of  the  stomach  is  not  actively  concerned  in  these  movements,  but 
serves  rather  as  a  reservoir  for  retaining  the  bulk  of  the  food,  while 
the  muscular  pyloric  region  is  the  apparatus  which  triturates  and 
macerates  the  food  and  forces  it  out  from  time  to  time  into  the 
duodenum.  According  to  the  observations  made  with  the  z-ray 
apparatus,  movements  begin  a  few  minutes  after  the  entrance  of 
food  into  the  stomach.  Small  contractions  start  in  the  middle 
region  of  the  stomach  and  run  toward  the  pylorus.  These  moving 
waves  of  contraction  appear  at  regular  intervals.  The  pyloric 
portion  becomes  lengthened  and  it  may  be  noticed  that  in  this 
region  the  peristaltic  waves  become  more  and  more  forcible  as 
digestion  progresses.  These  running  waves  or  rings  of  contraction 
serve  to  press  the  stomach  contents  against  the  pylorus.  According 
to  Cannon,  they  occur  in  the  cat  at  intervals  of  10  seconds  and  each 
wave  requires  about  20  seconds  to  reach  the  pylorus.  While  in 
human  beings,  to  judge  from  the  sounds  which  may  be  heard  upon 
ausculation  when  food  mixed  with  air  is  given,  they  occur  at  intervals 
of  about  20  seconds.  The  obvious  result  of  these  movements  is  to 
mix  the  food  thoroughly,  in  the  intermediate  and  pyloric  portions 
of  the  stomach,  with  the  acid  gastric  juice  and  to  reduce  it  to  a  thin, 
liquid  mass, — the  chyme.  At  certain  intervals  the  pyloric  sphincter 
relaxes  and  the  contraction  wave  squeezes  some  of  the  fluid  con- 
tents into  the  duodenum  with  considerable  force.  The  mechanism 
controlling  the  relaxation  of  this  sphincter  is  obscure.  It  does  not 
occur  with  the  approach  of  each  contraction  wave,  but  at  irregular 
intervals.  Cannon  connects  it  in  part  with  the  consistency  of  the 
food,  but  mainly  with  the  effect  of  the  hydrochloric  acid  in  the 

*  See  Osier,  "Journal  of  the  American  Medical  Association,"  Nov.  15, 
1902,  for  life  of  Beaumont  and  account  of  his  work. 

t  See  Cannon,  "American  Journal  of  Physiology,"  1,  359,  1898;  and  Roux 
and  Balthazard,  "Archives  de  Physiologic,"  10,  85,  1898. 

J  Hofmeister  and  Schiitz,  loc.  "cit. 

§  Moritz,  "Zeitschrift  f.  Biologic,"  32,  359,  1895. 


728  PHYSIOLOGY    OF   DIGESTION    AND    SECRETION. 

gastric  secretion.  Solid  objects  forced  against  the  pylorus  prevent 
relaxation  and  retard  the  passage  of  the  chyme  into  the  intestine. 
When  liquid  food  alone  is  taken  into  the  stomach  numerous  ob- 
servations, made  by  means  of  intestinal  fistulas,  prove  that  the 
material  may  be  forced  into  the  duodenum  within  a  few  minutes. 
Hydrochloric  acid  in  the  stomach  seems  to  favor  or  produce  a 
relaxation  of  the  pyloric  sphincter,  while  in  the  duodenum,  on  the 
contrary,  it  causes  a  contraction  of  the  sphincter.  In  this  way  it 
may  be  imagined  that  after  each  ejection  of  acid  chyme  the  sphinc- 
ter is  kept  closed  until  the  acid  material  in  the  duodenum  is  neutral- 
ized, and  so,  automatically,  a  mechanism  is  provided  by  means  of 
which  the  duodenum  is  charged  at  intervals  and  at  such  times  as  it 
is  prepared  to  receive  and  neutralize  a  new  quantity  of  the  chyme. 
According  to  this  description,  the  portion  of  the  food  toward  the 
pyloric  end  of  the  stomach  is  the  first  to  be  thoroughly  mixed  with 
the  gastric  juice,  and  to  be  broken  down  partly  by  digestion  and 
partly  by  the  mechanical  action  of  the  contractions.  This  portion, 
as  it  is  liquefied,  is  expelled,  and  its  place  is  taken  by  new  material 
forced  forward  from  the  fundic  end.  It  would  seem  that  this  latter 
portion  of  the  stomach  is  in  a  condition  of  tone,  and  the  pressure 
thus  put  upon  the  contents  is  sufficient  to  force  them  slowly  toward 
the  pyloric  end  as  this  becomes  emptied.  The  older  view  was  that 
the  contents  of  the  stomach  are  kept  in  a  general  rotary  movement 
so  as  to  become  more  or  less  uniformly  mixed;  but  Cannon's  obser- 
vations, and  also  those  of  Grutzner,*  indicate  that  the  material  at 
the  fundic  end  may  remain  undisturbed  for  a  long  time  and  thus 
escape  mixture  with  the  acid  gastric  juice,  so  far  at  least  as  the 

interior  of  the  mass  is  concerned. 
This  fact  is  of  importance  in  con-: 
nection  with  the  salivary  digestion 
of  the  starchy  foods.  Obviously, 
salivary  digestion  may  proceed  for 
a  time  in  the  fundic  end  without 
being  affected  by  the  acid  of  the 
stomach.  Grutzner  fed  rats  with 
food  of  different  colors  and  found 
that  the  successive  portions  were 
arranged  in  definite  strata.  The 
foo,f  firf  *aken  ^y  next  to  the 

food  was  given  in  three  portions  and  Walls  of  the  Stomach,  while  the 
colored  differently:  first,  black;  sec-  j.  ,.  , 

ond,  white   (indicated  by  vertical     succeeding  portions  were  arranged 
(indficated  by 


regularly  in  the  interior  in  a  con- 
centric   fashion,   as   shown  in   the 

figure.     Such  an  arrangement  of  the  food  is  more  readily  understood 

when  one  recalls  that  the  stomach  has  never  any  empty  space 

*  Grutzner,  "Archiv  f  .  die  gesammte  Physiologic,"  106,  463,  1905. 


MOVEMENTS    OF    THE    ALIMENTARY    CANAL.  729 

within;  its  cavity  is  only  as  large  as  its  contents,  so  that  the 
first  portion  of  food  eaten  entirely  fills  it  and  successive  por- 
tions find  the  wall  layer  occupied  and  are  therefore  received 
into  the  interior.  The  ingestion  of  much  liquid  must  interfere 
somewhat  with  this  stratification.  Cannon*  has  reported  some 
interesting  experiments  upon  the  relative  duration  of  gastric 
digestion  for  carbohydrates,  proteins,  and  fats  when  fed  separately 
and  combined.  The  foods  were  mixed  with  subnitrate  of  bismuth 
and  their  position  in  the  stomach  and  passage  into  the  intestine 
were  watched  by  means  of  the  Roentgen  rays.  It  was  found  that 
carbohydrate  food  begins  to  pass  out  from  the  stomach  soon  after 
ingestion,  and  requires  only  about  one-half  as  much  time  as  the  pro- 
teins for  complete  gastric  digestion.  Fats  remain  long  in  the 
stomach  when  taken  alone,  and  when  combined  with  the  other 
foodstuffs  markedly  delay  their  exit  through  the  pylorus.  This 
distinct  difference  in  the  main  foodstuffs  can  hardly  be  referred  to 
mere  mechanical  consistency,  since  the  fats  are  liquefied  by  the 
heat  of  the  body.  Cannon  has  shown  that  this  regulation  is  not 
effected  through  the  agency  of  the  extrinsic  nerves.  After  section  of 
the  splanchnics  and  vagi  the  difference  in  time  between  the  ejection 
of  carbohydrate  and  protein  material  still  exists,  so  that  the  con- 
trol in  this  matter  must  be  exerted  through  some  local  mechanism 
in  the  stomach  itself.  If,  in  a  given  diet,  the  carbohydrate  is  fed 
before  the  protein,  the  former,  having  the  position  of  advantage 
toward  the  pyloric  end,  will  be  ejected  promptly  into  the  intestine, 
while  the  protein  is  retained  for  gastric  digestion.  If  the  order  is 
reversed  and  the  protein  is  fed  first,  the  passage  of  the  carbohydrate 
out  of  the  stomach  will  be  retarded.  This  author  has  also  reported 
numerous  interesting  experiments,  of  medical  and  surgical  interest, 
which  indicate  that  the  motor  activity  of  both  stomach  and  intes- 
tines may  be  greatly  depressed  by  certain  conditions,  especially 
by  mechanical  handling  or  by  conditions  of  general  asthenia. 

Regarding  the  general  mechanism  of  the  stomach,  it  may  be 
pointed  out  that  it  forms  an  admirably  adapted  apparatus  for 
receiving  at  once,  or  within  a  short  period,  a  large  amount  of  food 
which  it  reduces  to  a  liquid  or  semiliquid  condition,  partly  by 
digestion,  partly  mechanically,  and  that  it  charges  the  intestine 
at  intervals  with  small  amounts  of  this  chyme  in  such  a  condition 
as  to  admit  of  rapid  digestion.  It  seems  obvious  that  without  the 
stomach  our  mode  of  eating  would  have  to  be  changed,  as  it  would 
not  be  possible  to  load  the  intestine  rapidly  with  a  large  supply  of 
food  such  as  is  consumed  at  an  ordinary  meal. 

*  Cannon,  "American  Journal  of  Physiology,"  12,  387,  1904.  For  a 
general  review  of  Cannon's  work,  see  "American  Journal  of  the  Medical 
Sciences,"  April,  1906. 


730  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

The  Relation  of  the  Nerves  to  the  Movements  of  the 
Stomach. — The  stomach  receives  nerve  fibers  from  two  sources, — 
the  vagi  and  the  splanchnics, — but  its  orderly  movements  are  merely 
regulated  through  these  extrinsic  fibers;  it  is  essentially  an  auto- 
matic organ.  Thus,  it  has  been  shown  that  the  excised  stomach 
(Hofmeister  and  Schutz),  when  kept  warm,  continues  to  execute 
regular  movements  which,  if  not  identical  with  those  observed  under 
normal  conditions,  have  at  least  an  orderly  sequence.  So  also  it 
would  appear  from  the  results  of  several  observers  *  that  gastric 
digestion  may  proceed  normally  both  as  regards  secretion  and 
movements  after  section  of  the  extrinsic  nerves.  We  may  regard 
the  stomach,  considered  as  a  motor  mechanism,  as  an  automatic 
organ  like  the  heart.  Its  stimuli  to  movement  arise  within  itself, 
but  these  movements  are  regulated  by  the  action  of  the  extrinsic 
nerve  fibers  so  as  to  adapt  them  to  varying  conditions.  Whether 
the  automaticity  is  a  property  of  the  plain  muscle  tissue  itself,  or 
depends  upon  the  rich  supply  of  intrinsic  nerve  ganglia  (plexuses  of 
Meissner  and  Auerbach),  is  a  question  that  cannot  be  answered 
definitely  at  present.  The  extrinsic  nerves  not  only  supply  the 
stomach  with  efferent  fibers,  motor  and  secretory,  but  also  carry 
afferent  fibers  from  the  stomach  to  the  central  nervous  system. 
Regarding  the  purely  efferent  action  of  the  extrinsic  nerves,  the 
results  of  numerous  experiments  seem  to  show  quite  conclusively 
that  in  general  the  fibers  received  along  the  vagus  path  are  motor, 
artificial  stimulation  of  them  causing  more  or  less  well-marked  con- 
tractions of  part  or  all  of  the  musculature  of  the  stomach.  It  has 
been  shown  that  the  sphincter  pylori  as  well  as  the  rest  of  the  muscu- 
lature is  supplied  by  motor  fibers  from  these  nerves.  The  fibers 
coming  through  the  splanchnics,  on  the  contrary,  are  mainly  inhib^ 
itory.  When  stimulated  they  cause  a  dilatation  of  the  contracted 
stomach  and  a  relaxation  of  the  sphincter  pylori.  Some  observers 
have  reported  experiments  which  seem  to  show  that  this  anatomical 
separation  of  the  motor  and  inhibitory  fibers  is  not  complete;  that 
some  inhibitory  fibers  may  be  found  in  the  vagi  and  some  motor 
fibers  in  the  splanchnics.  The  anatomical  courses  of  these  fibers 
are  insufficiently  known,  but  there  seems  to  be  no  question  as  to  the 
existence  of  the  two  physiological  varieties.  Through  their  activity, 
without  doubt,  the  movements  of  the  stomach  may  be  influenced, 
favorably  or  unfavorably,  by  conditions  directly  or  indirectly  affect- 
ing the  central  nervous  system.  Wertheimer  f  has  shown  experi- 
mentally that  stimulation  of  the  central  end  of  the  sciatic  or  the 
vagus  nerve  may  cause  reflex  inhibition  of  the  tonus  of  the  stomach, 

*  See  Heidenhain  in  Hermann's  "Handbuch  der  Physiologic,"  vol.  v., 
p.  118.    Also  Cannon,  "American  Journal  of  Physiology,"  1906. 

f  "Archiv  de  physiologic  normale  et  pathologique,"  1892,  p.  379. 


MOVEMENTS    OF    THE    ALIMENTARY    CANAL.  731 

and  Doyon*  has  confirmed  this  result  in  cases  in  which  the  move- 
ments and  tonicity  of  the  stomach  were  first  increased  by  the  action 
of  pilocarpin  and  strychnin.  Cannon,  in  his  observations  upon  cats, 
found  that  all  movements  of  the  stomach  ceased  as  soon  as  the 
animal  showed  signs  of  anxiety,  rage,  or  distress. 

Hunger  Contractions. — After  the  stomach  has  been  empty  for 
a  certain  time  we  experience  sensations  of  hunger  that  are  more 
or  less  of  a  subpainful  character  and  are,  therefore,  frequently 
designated  as  "hunger-pains."  ,  These  sensations  appear  and  dis- 
appear at  irregular  intervals  until  food  is  taken  into  the  stomach. 
Cannon  and  Washburn  j  first  showed  that  these  sensations  appear 
simultaneously  with  contractions  of  the  stomach,  and  they  sug- 
gested that  the  hunger  contractions  cause  the  hunger-pains. 
These  particular  movements  have  been  investigated  since  by 
Carlson  J  upon  a  man  with  a  permanent  gastric  fistula.  He  finds 
that  the  hunger  contractions  appear  in  groups,  lasting  for  a  certain 
time,  with  intervening  periods  of  quiescence.  In  each  group  the 
beginning  contractions  are  weak  and  slow,  but  there  is  an  increase 
in  amplitude  or  vigor  during  the  period,  so  that  the  climax  is 
reached  at  the  end  of  the  period.  Chemical  or  mechanical  stimu- 
lation of  the  gastric  mucosa  or  even  the  chewing  of  palatable  food 
inhibits  the  hunger  contractions.  The  hunger  contractions,  like 
the  digestive  contractions,  continue  when  the  extrinsic  nerves  are 
severed.  Presumably,  therefore,  both  kinds  of  movement  are 
initiated  and  controlled  through  the  intrinsic  nervous  apparatus. 
The  chief  difference  in  character  between  the  digestive  and  the 
hunger  contractions  seems  to  lie  in  the  fact  that  the  former  involve 
mainly  the  antral  end,  while  the  latter  are  described  as  starting 
from  the  region  of  the  cardiac  orifice  and  spreading  as  a  peristaltic 
wave  over  the  whole  stomach.  It  is  stated  §  that  as  the  stomach 
empties  itself  after  a  meal  the  peristaltic  waves  of  contraction  arise 
nearer  and  nearer  to  the  cardiac  end  and  pass  over  gradually  into 
the  hunger  contractions  characteristic  of  the  empty  stomach. 

Movements  of  the  Intestines.— The  muscles  of  the  small  and 
the  large  intestine  are  arranged  in  two  layers, — an  outer  longitudinal 
and  an  inner  circular  coat, — while  between  these  coats  and  in  the 
submucous  coat  there  are  present  the  nerve-plexuses  of  Auerbach 
and  Meissner.  The  general  arrangement  of  muscles  and  nerves  is 
similar,  therefore,  to  that  prevailing  in  the  stomach,  and  in  accor- 
dance with  this  we  find  that  the  physiological  activities  exhibited 
are  of  much  the  same  character,  only,  perhaps,  not  quite  so  complex. 

*  "  Archiv  de  physiologie  normale  et  pathologique,"  1895,  p.  374. 
t  Cannon  and  Washburn,  "American  Journal  of  Physiology,"  29,  441, 1912. 
j  Carlson,  "The  Control  of  Hunger  in  Health  and  Disease,"  Chicago,  1916, 
and  numerous  papers  in  "The  American  Journal  of  Physiology,"  vols.  31-42. 
§  Rogers  and  Hardt,  "American  Journal  of  Physiology,"  38,  274,  1915. 


732  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

Two  main  forms  of  intestinal  movement  have  been  distin- 
guished,— the  peristaltic  and  the  pendular  or  rhythmic. 

Peristalsis. — The  peristaltic  movement  consists  in  a  constriction 
of  the  walls  of  the  intestine,  which,  beginning  at  a  certain  point, 
passes  downward  away  from  the  stomach,  from  segment  to  segment, 
while  the  parts  behind  the  advancing  zone  of  constriction  gradually 
relax.  The  wave  of  constriction  may  be  recorded  by  the  use  of 
suitable  apparatus.  When  thus  recorded  it  is  found  that  the  ad- 
vancing area  of  constriction  is  preceded  by  an  area  of  inhibition 
or  relaxation,  so  that  the  peristaltic  movement  consists  of  two  parts, 
following  in  a  definite  sequence,  which  seem  to  combine  to  facili- 
tate the  movement  onward  of  the  intestinal  contents;  for  it  is 
obvious  that  the  wave  of  constriction  will  be  more  effective  in 
forcing  the  contents  forward  if  just  in  front  of  it  the  intestine  is 


Fig.  285. — Peristaltic  contraction  of  the  small  intestine  (dog).  The  horizontal  line  gives 
the  time  in  seconds.  The  curve  was  obtained  by  recording  the  diameter  of  the  intestine  at 
a  given  point  during  the  passage  of  a  peristaltic  wave.  It  will  be  seen  that  there  was  first'  a 
dilatation  (wave  of  inhibition),  followed  by  a  strong  contraction.  The  smaller  waves  on  the 
intestinal  curve  are  due  to  the  effect  of  the  respiratory  movements  on  the  recording  mechanism. 

relaxed  by  inhibition  of  the  tonicity  of  the  muscular  coat  (Fig.  285). 
Bayliss  and  Starling,*  to  whom  we  owe  the  discovery  of  this  two- 
fold character  of  the  movement,  regard  it  as  a  reflex  which  is  con- 
trolled within  the  intestinal  wall  itself  through  its  intrinsic  ganglia 
and  their  afferent  and  efferent  connections.  When  a  bolus  is 
inserted  into  the  intestine  at  any  point  its  effect  upon  the  nerve- 
fibers  is  such  as  to  cause  a  reflex  contraction  of  the  muscle  above  the 
bolus,  that  is,  toward  the  stomach,  and  a  reflex  inhibition  or 
dilatation  below.  They  speak  of  this  definite  relationship  as  the 
law  of  the  intestine;  it  is  described  also  under  the  name  my  en- 
teric reflex.  It  is  obvious  that  the  circular  layer  of  muscles  is 
chiefly  involved  in  peristalsis,  since  constriction  can  only  be  pro- 
duced by  contraction  of  this  layer.  To  what  extent  the  longitudi- 
nal muscles  enter  into  the  movement  is  not  definitely  determined. 
The  term  "antiperistalsis"  is  used  to  describe  the  same  form  of 
*  Bayliss  and  Starling,  "Journal  of  Physiology,"  24,  99, 1899. 


MOVEMENTS    OF    THE    ALIMENTARY    CANAL.  733 

The  term  "antiperistalsis"  is  used  to  describe  the  same  form  of 
movement  running  in  the  opposite  direction — that  is,  toward  the 
stomach.  Antiperistalsis  is  said  not  to  occur  under  normal  condi- 
tions ;  it  has  been  observed  in  isolated  pieces  of  intestine  or  in  the  ex- 
posed intestine  of  living  animals  when  stimulated  artificially  or  after 
complete  intestinal  obstruction  (Cannon).  The  peristaltic  wave 
normally  passes  downward,  and  that  this  direction  of  movement 
is  dependent  upon  some  definite  arrangement  in  the  intestinal 
walls  is  shown  by  the  experiments  of  Mall*  upon  reversal  of  the 
intestines.  In  these  experiments  a  portion  of  the  small  intestine 
was  resected,  turned  around,  and  sutured  in  place  again,  so  that  in 
this  piece  what  was  the  lower  end  became  the  upper  end.  In  those 
animals  that  made  a  good  recovery  the  nutritive  condition  gradu- 
ally became  very  serious,  and  when  the  animals  were  killed  and 
examined  it  was  found  that  there  was  an  accumulation  of  food  at 
the  stomach  end  of  the  reversed  piece  of  intestine,  and  that  this 
region  showed  marked  dilatation. 

The  peristaltic  movements  of  the  intestines  may  be  observed 
upon  living  animals  when  the  abdomen  is  opened.  If  the  operation 
is  made  in  the  air  and  the  intestines  are  exposed  to  its  influence,  or 
if  the  conditions  of  temperature  and  circulation  are  otherwise 
disturbed,  the  movements  observed  are  often  violent  and  irregular. 
The  peristalsis  runs  rapidly  along  the  intestines  and  may  pass  over 
the  whole  length  in  about  a  minute;  at  the  same  time  the  con- 
traction of  the  longitudinal  muscles  gives  the  bowels  a  peculiar 
writhing  movement.  Movements  of  this  kind  are  evidently 
abnormal,  and  only  occur  in  the  body  under  the  strong  stimulation 
of  pathological  conditions.  Normal  peristalsis,  the  object  of  which 
is  to  move  the  food  slowly  along  the  alimentary  tract,  is  quite  a 
different  affair.  Observers  all  agree  that  the  wave  of  contraction 
is  gentle  and  progresses  slowly,  although  at  different  rates  perhaps 
in  different  parts  of  the  intestine.  The  force  of  the  contraction 
as  measured  by  Cashf  in  the  dog's  intestine  is  very  small.  A 
weight  of  five  to  eight  grams  was  sufficient  to  check  the  onward 
movement  of  the  substance  in  the  intestine  and  to  set  up  violent, 
colicy  contractions  which  caused  the  animal  evident  uneasiness. 
The  time  required  for  the  passage  of  food  through  the  small  in- 
testine must  vary  with  its  amount  and  character.  From  obser- 
vations made  upon  man  with  the  o>ray,  Hertz  estimates  that  on 
the  average  it  requires  about  4f  hours.  After  a  meal,  therefore, 
we  may  imagine  that  at  about  the  time  the  stomach  has  finished 
discharging  its  contents  into  the  duodenum  the  first  portions 
have  reached  the  ileocecal  valve.  That  is  to  say,  a  column  of 

*  "Johns  Hopkins  Hospital  Reports,"  1,  93,  1896. 

t ' 'Proceedings  of  the  Royal  Society,"  London,  41,  1887. 


734  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

food,  broken  into  separate  segments,  stretches  at  one  time  practi- 
cally along  the  whole  length  of  the  small  intestine. 

Mechanism  of  the  Peristaltic  Movement. — The  means  by  which 
the  peristaltic  movement  makes  its  orderly  forward  progression 
have  not  been  determined  beyond  question.  The  simplest  explana- 
tion would  be  to  assume  that  an  impulse  is  conveyed  directly  from 
cell  to  cell  in  the  circular  muscular  coat,  so  that  a  contraction  started 
at  any  point  would  spread  by  direct  conduction  of  the  contraction 
change.  This  theory,  however,  does  not  explain  satisfactorily  the 
normal  conduction  of  the  wave  of  contraction  always  in  one  direc- 
tion, nor  the  fact  that  the  wave  of  contraction  is  preceded  by  a 
wave  of  inhibition.  Moreover,  Bayliss  and  Starling  state  that, 
although  the  peristaltic  movements  continue  after  section  of  the 
extrinsic  nerves, — indeed,  become  more  marked  under  these  con- 
ditions,— the  application  of  cocain  or  nicotin  prevents  their  oc- 
currence. Since  these  substances  may  be  supposed  to  act  on  the 
intrinsic  nerves,  it  is  probable  that  the  co-ordination  of  the  move- 
ment is  effected  through  the  local  nerve  ganglia,  but  our  knowledge 
of  the  mechanism  and  physiology  of  these  peripheral  nerve-plexuses 
is  as  yet  quite  incomplete. 

Rhythmical  Movements. — In  addition  to  the  peristaltic  wave  a 
second  kind  of  movement  may  be  observed  in  the  small  intestines. 
It  consists  essentially  in  a  series  of  local  constrictions  of  the  intes- 
tinal wall,  the  constrictions  occurring  rhythmically  at  those  points 
at  which  masses  of  food  lie. 

Cannon  *  has  studied  these  movements  most  successfully  by 


Fig.  286. — Diagram  to  show  the  effect  of  the  rhythmical  constricting  movements  of 
the  small  intestine  upon  the  contained  food.  A  string  of  food  (1)  is  divided  suddenly  into 
a  series  of  segments  (2)  ;  each  of  the  latter  is  again  divided  and  the  process  is  repeated  a 
number  of  times  (3  and  4).  Eventually  a  peristaltic  wave  sweeps  these  segments  forward 
a  certain  distance  and  gathers  them  again  into  a  long  string,  as  in  (1).  The  process  of 
segmentation  is  then  repeated  as  described  above.  (Cannon.) 

means  of  the  Roentgen  rays.  He  finds  that  as  a  result  of  these 
contractions  the  masses  or  strings  of  food  lying  in  the  intestine  are 
suddenly  segmented,  repeatedly  and  in  a  definite  manner,  into  a 
number  of  small  pieces,  which  move  to  and  fro  as  the  pieces  combine 
and  are  again  separated  (see  Fig.  286).  These  segmentations  may 
proceed  at  the  rate  of  thirty  per  minute  for  a  certain  time,  and  the 

*  Cannon,  "American  Journal  of  Physiology,"  6,  251,  1902. 


MOVEMENTS    OF   THE    ALIMENTARY    CANAL.  735 

apparent  result  is  that  the  material  is  well  mixed  with  the  digestive 
secretions  and  is  brought  thoroughly  into  contact  with  the  absorp- 
tive walls.  During  these  rhythmical  contractions  there  is  no  steady 
progression  of  the  food;  it  remains  in  the  same  region,  although 
subjected  to  repeated  divisions.  From  time  to  time  tne  separated 
pieces  are  caught  by  an  advancing  peristaltic  wave,  moved 
forward  a  certain  distance,  and  gathered  again  into  a  new  mass. 
In  this  new  location  the  rhythmical  contractions  again  segment 
and  churn  the  mass  before  a  new  peristaltic  wave  moves  it  on. 
According  to  this  description,  the  rhythmical  movements  are 
local  contractions  (mainly  of  the  circular  muscles)  which  seem 
to  be  due  to  the  local  distention  caused  by  the  food.  They  occur 
rhythmically  for  a  certain  period  and  then  cease  until  a  new  series 
is  started,  and  it  is  obvious  that  they  must  play  a  very  important 
part  in  promoting  both  the  digestion  and  absorption  of  the  food. 
Mall*  has  suggested  that  these  rhythmical  contractions  of  the 
circular  coats  may  also  act  as  a  pumping  mechanism  upon  the 
venous  plexuses  in  the  walls  and  thus  aid  in  driving  the  blood  into 
the  portal  system.  Similar  movements  have  been  observed 
in  the  human  being,  f  The  curious  observation  is  reported t 
that  during  the  period  of  fasting  (dog)  the  whole  gastro-intestinal 
canal,  although  empty,  shows  at  intervals  rhythmical  con- 
tractions of  its  musculature  which  may  last  for  twenty  to  thirty 
minutes  (see  p.  796). 

Cannon  suggests  a  new  and  convenient  nomenclature  for  the  movements 
of  the  stomach  and  intestines  as  follows : 

(1)  Rhythmic  segmentations. — The  rhythmic  localized  contractions  de- 
cribed  in  the  preceding  paragraph.     Exhibited  throughout  the  small  intestine. 

(2)  Diastalsis. — Downward  moving  wave  of  contraction  with  a  preceding 
wave  of  inhibition  (myenteric  reflex).    Exhibited  chiefly  in  the  small  intestine. 

(3)  Anastalsis. — Upward  moving  wave   of  contraction  without  a  pre- 
ceding phase  of  inhibition     Exhibited  chiefly  in  the  proximal  colon. 

(4)  Katastalsis. — Downward    moving    wave    of    contraction   without   a 
preceding  phase  of  inhibition.     Exhibited  chiefly  in  the  stomach. 

Movements  of  the  Intestinal  Villi. — Hambleton  §  calls  attention 
to  the  fact  that  if  the  intestine  of  a  living  animal  is  opened  and 
spread  out  under  suitable  conditions  so  that  the  villi  may  be 
examined  under  a  binocular  microscope,  it  can  be  shown  that  they 
exhibit  active  movements  of  two  kinds:  First,  lashing  movements 
from  side  to  side  in  various  directions;  second,  what  might  be 
called  pumping  movements,  in  which  the  villi  are  alternately 
extended  and  retracted.  Doubtless  these  movements  are  due  to 
the  contractions  of  the  muscular  slips,  which  run  into  the  stroma  of 

*  Mall,  "Johns  Hopkins  Hospital  Reports,"  1896,  i.,  37.^ 

t  Hertz,  loc.  tit. 

i  Boldireff,  "Archives  des  sciences  biologiques,"  11,  1,  1905. 

§  Hambleton,  "American  Journal  of  Physiology,"  34,  446,  1914. 


736  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

the  villi  from  the  muscularis  mucosse.  If  we  can  suppose  that 
they  occur  during  normal  digestion,  it  is  evident  that  they  add  a 
mechanical  factor,  not  hitherto  considered,  which  must  help  ma- 
terially in  the  absorption  of  the  products  of  digestion. 

The  Nervous  Control  of  the  Intestinal  Movements. — There 
is  some  evidence  to  show  that  the  rhythmical  contractions  of  the 
intestines  are  muscular  in  origin  (myogenic),  while  the  more  co- 
ordinated peristaltic  movements  depend  upon  the  intrinsic  nervous 
mechanism.  The  intestine  is,  however,  not  dependent  for  either 
movement  upon  its  connections  with  the  central  nervous  system. 
Like  the  stomach,  it  is  an  automatic  organ  whose  activity  is  simply 
regulated  through  its  extrinsic  nerves. 

The  small  intestine  obtains  its  supply  of  extrinsic  nerve-fibers 
from  two  sources,  a  bulbar  autonomic  supply  by  way  of  the  vagi 
and  a  thoracic  autonomic  supply  by  way  of  the  splanchnic  nerves 
and  the  superior  mesenteric  ganglia.  Stimulation  of  the  vagi  causes 
contraction  or  increased  tonus  in  the  intestinal  musculature,  while 
stimulation  of  the  splanchnics,  on  the  contrary,  causes  relaxation  or 
inhibition  of  tonus.*  The  paths  of  these  fibers  through  the  central 
nervous  system  are  not  known,  but  there  are  evidently  connections 
extending  to  the  higher  brain  centers,  since  psychical  states  are 
known  to  influence  the  movements  of  the  intestine,  and  according 
to  some  observers  stimulation  of  portions  of  the  cerebral  cortex 
may  produce  movements  or  relaxation  of  the  walls  of  the  small  and 
large  intestines. 

Effect  of  Various  Conditions  upon  the  Intestinal  Move- 
ments.— Experiments  have  shown  that  the  movements  of  the  in- 
testines may  be  evoked  in  many  ways  in  addition  to  direct  stimu- 
lation of  the  extrinsic  nerves.  Chemical  stimuli  may  be  applied 
directly  to  the  intestinal  wall.  Mechanical  stimulation — pinching, 
for  example,  or  the  introduction  of  a  bolus  into  the  intestinal 
cavity — may  start  peristaltic  movements.  Violent  movements 
may  be  produced  also  by  shutting  off  the  blood-supply,  and  again 
temporarily  when  the  supply  is  re-established.  A  condition  of 
dyspnea  may  also  start  movements  in  the  intestines  or  in  some 
cases  inhibit  movements  which  are  already  in  progress,  the  stimu- 
lus in  this  case  seeming  to  act  upon  the  central  nervous  system  and 
to  stimulate  both  the  motor  and  the  inhibitory  fibers.  Oxygen  gas 
within  the  bowels  tends  to  suspend  the  movements  of  the  intes- 
tine, while  CO2,  CH4,  and  H2S  act  as  stimuli,  increasing  the  move- 
ments. Organic  acids,  such  as  acetic,  propionic,  formic,  and 
caprylic,  which  may  be  formed  normally  within  the  intestine  as 
the  result  of  bacterial  action,  act  also  as  strong  stimulants. 

*  For  a  discussion  of  the  innervation  of  the  small  and  large  intestine,  see 
Gaskell,  "The  Involuntary  Nervous  System/'  1916. 


MOVEMENTS    OF   THE    ALIMENTARY    CANAL.  737 

Movements  of  the  Large  Intestine. — The  opening  from  the 
small  intestine  into  the  large  is  controlled  both  by  the  ileocecal 
valve  and  by  a  sphincter,  the  ileocecal  or  ileocolic  sphincter. 
It  is  stated  that  this  sphincter  is  normally  in  tonus  and  that 
its  condition  of  tonus  is  regulated  through  the  thoracic  autonomic 
fibers  received  by  way  of  the  splanchnic  nerve  and  superior  mesen- 
teric  ganglion.  Stimulation  of  the  splanchnic  nerve  is  said  to  cause 
contraction  of  the  ileocolic  sphincter.*  The  musculature  in  the 
large  intestine  has  the  same  general  arrangement  as  in  the  small,  and 
the  usual  view  has  been  that  the  movements  are  similar,  although 
more  infrequent,  so  that  the  material  received  from  the  small  intes- 
tine is  slowly  moved  along  while  becoming  more  and  more  solid 
from  the  loss  of  water.  The  contents  of  the  ascending  colon  are 
soft  and  semiliquid,  but  in  the  distal  end  of  the  transverse  colon 
they  attain  the  consistency  of  the  feces.  Bayliss  and  Starling 
state  that  their  law  of  intestinal  peristalsis  holds  in  this  portion  of 
the  intestine, — that  is,  local  excitation  causes  a  constriction  above 
and  a  dilatation  below  the  point  stimulated.  Cannon,  f  from  his 
studies  of  the  normal  movements  in  cats,  as  seen  by  the  Roentgen 
rays,  comes  to  the  conclusion  that  the  movements  in  the  proximal 
portion  of  the  large  intestine  show  a  marked  peculiarity.  He 
divides  the  large  intestine  into  two  parts;  in  the  second,  correspond- 
ing roughly  to  the  descending  and  distal  portion  of  the  transverse 
colon,  the  food  is  moved  toward  the  rectum  by  peristaltic  waves. 
A  number  of  constrictions  may  be  seen  simultaneously  within  a 
length  of  some  inches.  In  the  ascending  colon  and  cecum,  on  the 
contrary,  the  most  frequent  movement  is  that  of  antiperistalsis. 
The  food  in  this  portion  of  the  canal  is  more  or  less  liquid  and  its 
presence  sets  up  running  waves  of  constriction,  which  pass  toward 
the  ileocecal  valve.  These  waves  occur  in  groups  separated  by 
periods  of  rest.  They  seem  to  originate  from  a  constricted  ring 
which  pulsates,  each  contraction  starting  an  anastaltic  wave. 
The  presence  of  the  ileocecal  valve  prevents  the  material  from 
being  forced  back  into  the  small  intestine.  The  value  of  this 
peculiar  reversal  of  the  normal  movement  of  the  bowels  at  this 
particular  point  would  seem  to  lie  in  the  fact  that  it  delays  the 
passage  of  the  material  toward  the  rectum,  and  by  thoroughly 
mixing  it  gives  increased  opportunities  for  the  completion  of  the 
processes  of  digestion  and  absorption.  In  animals  with  a  saccu- 
lated  colon  the  separate  sacs  or  haustra  may  exhibit  rhythmic 
contractions  somewhat  similar  to  the  rhythmic  segmentations 
in  the  small  intestine.  J  These  movements  (haustal  churning) 

*  Elliott,  "Journal  of  Physiology,"  1904,  31,  157. 

t  Cannon,  loc.  cit. 

t  Elliott  and  Barclay-Smith,  "Journal  of  Physiology,"  31,  272,  1904. 

47 


738 


PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 


would  seem  to  favor  also  the  processes  of  absorption.  Hertz 
estimates  that  in  man  the  food  requires  about  2  hours  to  pass 
from  the  ileocecal  valve  to  the  hepatic  flexure  and  about  4J 
hours  to  reach  the  splenic  flexure.  As  the  colon  becomes  filled 
some  of  the  material  penetrates  into  the  descending  part,  where 
the  normal  peristalsis  carries  it  very  slowly  toward  the  rectum. 

The  large  intestine  receives  its  nerve  supply  from  two  sources 
(Fig.  287) :    (1)  Fibers  which  leave  the  spinal  cord  in  the  lumbar 


Ganglion  mesenferieum  uiftriui 
Branches  to  C< 


Fig.  287. — Schema  to  show  the  innervation  of  the  rectum  and  internal  sphincter 
of  the  anus,  and  the  formation  of  the  hypogastric  plexus.  (After  Frankl-Hochwart  and 
Frehlich.) 

nerves  (second  to  fifth  in  cat),  pass  to  the  sympathetic  chain,  and 
thence  to  the  inferior  mesenteric  ganglia,  which  probably  form 
the  termination  of  the  preganglionic  fibers.  From  this  point 
the  path  is  continued  by  fibers  running  in  the  hypogastric  nerves 
and  plexus.  Stimulation  of  these  fibers  has  given  different  results 
in  the  hands  of  various  observers,  but  the  general  view  *  is  that  they 
are  inhibitory.  (2)  Fibers  that  leave  the  cord  in  the  sacral  nerves 
(second  to  fourth)  form  part  of  the  nervi  erigentes  or  pelvic  nerves 
and  enter  into  the  hypogastric  plexus.  When  stimulated  these 
fibers  cause  contractions  of  the  muscular  coats;  they  may  be  re- 

*  Langley  and  Anderson,  "Journal  of  Physiology,"  18,  67,  1895.  Bayliss 
and  Starling,  ibid.,  26, 107, 1900:  Gaskell,  "The  Involuntary  Nervous  System," 
1916. 


MOVEMENTS    OF    THE    ALIMENTARY    CANAL.  739 

garded,  therefore,  as  motor  fibers.  As  in  the  case  of  the  small 
intestine  and  stomach,  we  may  assume  that  these  motor  and  in- 
hibitory fibers  serve  for  the  reflex  regulation  and  adaptation  of  the 
movements.  In  this  connection  attention  may  be  called  to  the 
difference  in  innervation  between  the  stomach  and  small  intestine, 
on  the  one  hand,  and  the  colon  and  rectum  on  the  other.  The 
former  receive  their  extrinsic  motor  fibers  mainly  if  not  entirely 
through  the  vagus  (bulbar  autonomic),  while  the  latter  receive  their 
motor  fibers  mainly,  if  not  entirely,  through  the  pelvic  nerve 
(sacral  autonomies),  arising  near  the  extreme  lower  end  of  the  cord. 
The  small  intestine  receives  its  inhibitory  fibers  through  the 
splanchnic  nerve  and  superior  mesenteric  ganglion  (thoracic 
autonomies),  while  the  colon  and  rectum  get  their  inhibitory  fibers 
through  splanchnic  branches  that  connect  with  the  inferior  mesen- 
teric ganglion  (thoracic  autonomies). 

Defecation. — The  undigested  and  indigestible  parts  of  the 
food,  together  with  some  of  the  debris  and  secretions  from  the 
alimentary  tract  eventually  reach  the  sigmoid  flexure  and 
rectum.  Authorities  differ  as  to  whether  the  rectum  normally 
contains  fecal  material  or  not.  According  to  the  observations 
of  Hertz,*  made  upon  man  by  means  of  z-rays,  fecal  material 
is  normally  absent  from  the  rectum  except  just  before  defeca- 
tion. It  seems  probable  that  a  distinct  desire  to  defecate 
is  felt  only  when  the  feces  have  actually  entered  the  rec- 
tum and  produced  some  distension.  The  fecal  material  is 
retained  within,  the  rectum  by  the  action  of  the  two  sphincter 
muscles  which  close  the  anal  opening.  One  of  these  muscles, 
the  internal  sphincter,  is  a  strong  band  of  the  circular  layer  of 
involuntary  muscle  which  forms  one  of  the  coats  of  the  rectum. 
When  the  rectum  contains  fecal  material  this  muscle  is  thrown 
into  a  condition  of  tonic  contraction  until  the  act  of  defecation 
begins,  when  it  is  relaxed.  The  external  sphincter  ani  is  com- 
posed of  striated  muscle  tissue  and  is  under  the  control  of  the 
will  to  a  certain  extent.  It  is  supplied  by  a  motor  nerve,  the 
Nn.  hemorrhoidales  inferiores,  arising  from  the  N.  pudendus 
and  eventually  from  the  sacral  spinal  nerves.  This  muscle, 
therefore,  like  striated  muscle  in  general,  is  innervated  directly 
from  the  spinal  cord,  but  it  possesses  properties  which  are  to 
some  extent  intermediate  between  those  of  plain  and  of  striated 
muscle.  For  example,  it  differs  from  the  latter  and  resembles 
the  former  in  the  fact  that  it  does  not  atrophy  after  section  of 
its  motor  nerve;  it  is  much  less  sensitive  to  the  paralyzing  action 
of  curare  than  the  typical  striated  muscle,  and  it  is  stated  that 
its  curve  of  contraction,  when  it  is  stimulated  through  its  nerve, 

*  Hertz,  "Guy's  Hospital  Reports,"  61,  389,  1907. 


740 


PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 


exhibits  a  long  latent  period  and  a  slow  contraction  and  relaxa- 
tion. Both  the  internal  and  the  external  sphincter  are  normally 
in  tonus  and  unite  in  protecting  the  anal  opening.  The  force 
of  the  tonic  contraction  of  the  internal  is  somewhat  less  (30  to 
60  per  cent.)  than  that  of  the  external  sphincter.  The  internal 
sphincter,  like  the  rest  of  the  musculature  of  the  rectum,  receives  a 
double  nerve  supply,  one  set  of  fibers  coming  to  it  through  the 
pelvic  nerve  (sacral  autonomies)  and  one  set  through  the  hypo- 
gastric  nerve  by  way  of  the  inferior  mesenteric  ganglion  (thoracic 
autonomies).  The  action  of  the  efferent  fibers  in  these  nerves 
has  been  a  matter  of  dispute,  and  possibly  the  results  may  differ 
in  different  animals.  According  to  one  account  the  sphincter 
responds  in  the  same  way  as  the  rest  of  the  circular  muscle  of  the 
rectum,  that  is  to  say,  it  is  thrown  into  contraction  by  stimulation 
of  the  pelvic  nerve,  and  is  inhibited  by  stimulation  of  the  hypo- 
gastric  nerve.  According  to  others  the  effects  are  just  the  reverse.* 
Following  the  accounts  given  by  the  first  group  of  observers  it  is 
stated  that  each  of  these  sets  of  fibers  may  be  acted  upon  reflexly, 
for  example,  by  stimulation  of  the  sensory  nerves  in  the  sciatic. 
The  reflex  takes  place  in  this  case  through  the  lower  portion  of 
the  cord.  Both  the  hypogastric  nerve  and  the  N.  erigens  con- 
tain also  afferent  fibers.  Stimulation  of  the  central  end  of  the 
severed  N.  erigens  gives  a  reflex  inhibition  through  the  hypo- 
gastric  nerve,  and  stimulation  of  the  central  stump  of  the  cut 
hypogastric  causes  a  reflex  contraction  through  the  N.  erigens. 
The  act  of  defecation  as  it  occurs  normally  is  partly  a  voluntary 
and  partly  an  involuntary  act.  The  involuntary  act  consists  in 
peristaltic  contractions  of  the  rectum  or,  indeed,  of  the  whole 
colon,  together  with  an  inhibition  of  the  sphincters.  Whether 
the  inhibition  of  the  sphincters  is  normally  entirely  an  involuntary 
reflex  cannot  be  stated  definitely.  No  doubt  the  sensory  stimuli 
arising  from  the  accumulation  of  fecal  material  would  eventually 
cause  in  this  way  a  relaxation  of  the  sphincters,  but  the  act  of 
defecation  usually  takes  place  before  such  a  strong  necessity  arises. 
It  is  initiated  usually  by  a  voluntary  act,  and  it  is  possible  that  in 
such  cases  the  relaxation  of  both  sphincters  may  be  effected  by 
voluntary  inhibition  acting  upon  the  spinal  centers. 

The  voluntary  factor  in  defecation  consists  mainly  in  the 
contraction  of  the  abdominal  muscles.  When  these  latter 
muscles  are  contracted  and  at  the  same  time  the  diaphragm  is 
prevented  from  moving  upward  by  the  closure  of  the  glottis, 
the  increased  abdominal  pressure  is  brought  to  bear  upon  the 
abdominal  and  pelvic  viscera,  and  aids  strongly  in  pressing  the 

*  Consult  Frankl-Hochwart  and  Frohlich,  "Archiv  f.  de  ges  Physiologie," 
81,  420,  1900,  and  GaskeU,  loc.  cit. 


MOVEMENTS    OF    THE    ALIMENTARY    CANAL.  741 

contents  of  the  descending  colon  and  sigmoid  flexure  into  the 
rectum.  The  pressure  in  the  abdominal  cavity  is  still  further 
increased  if  a  deep  inspiration  is  first  made  and  then  maintained 
during  the  contraction  of  the  abdominal  muscles.  Hertz,  on 
the  basis  of  his  skiagraphic  observations,  insists  that  simul- 
taneously with  the  contraction  of  the  abdominal  muscles  and 
the  closure  of  the  glottis  the  diaphragm  is  also  contracted  and 
thus  aids  in  bringing  pressure  to  bear  upon  the  pelvic  organs. 
Although  the  act  of  defecation  is  normally  initiated  by  voluntary 
effort,  it  may  also  be  carried  out  as  a  purely  involuntary  reflex 
when  the  sensory  stimulus  is  sufficiently  strong.  Goltz*  has 
shown  that  in  dogs  in  which  the  spinal  cord  had  been  severed 
in  the  lower  thoracic  region  defecation  was  performed  normally. 
In  later  experiments,  in  which  the  entire  spinal  cord  was  removed 
except  in  the  cervical  and  upper  part  of  the  thoracic  region,  it 
was  found  that  the  animal,  after  it  had  recovered  from  the 
operation,  had  normal  movement  once  or  twice  a  day,  indicating 
that  the  rectum  and  lower  bowels  acted  by  virtue  of  their 
intrinsic  mechanism.  An  interesting  result  of  these  experi- 
ments was  the  fact  that  the  external  sphincter  suffered  no 
atrophy,  although  its  motor  nerve  was  destroyed,  and  that  it 
eventually  regained  its  tonic  activity. 

It  would  seem  that  the  whole  act  of  defecation  is,  at  bottom, 
an  involuntary  reflex.  The  physiological  center  for  the  move- 
ment probably  lies  in  the  lumbar  cord,  and  it  has  sensory  and 
motor  connections  with  the  rectum  and  the  muscles  of  defecation. 
But  this  center  is  probably  provided  also  with  intraspinal  con- 
nections with  the  centers  of  the  cerebrum,  through  which  the 
act  may  be  controlled  by  voluntary  impulses  and  by  various 
psychical  states;  the  effect  of  emotions  upon  defecation  being 
a  matter  of  common  knowledge.  In  infants  the  essentially  in- 
voluntary character  of  the  act  is  well  known. 

Vomiting. — The  act  of  vomiting  causes  an  ejection  of  the  con- 
tents of  the  stomach  through  the  esophagus  and  mouth  to  the 
exterior.  It  was  long  debated  whether  the  force  producing  this 
ejection  comes  from  a  strong  contraction  of  the  walls  of  the  stom- 
ach itself  or  whether  it  is  due  mainly  to  the  action  of  the  walls  of 
the  abdomen.  A  forcible  spasmodic  contraction  of  the  abdominal 
muscles  takes  place,  as  may  easily  be  observed  by  any  one  upon 
himself,  and  it  is  now  believed  that  the  contraction  of  these  muscles 
is  the  principal  factor  in  vomiting.  Magendie  found  that  if  the 
stomach  was  extirpated  and  a  bladder  containing  water  was  sub- 
stituted in  its  place  and  connected  with  the  esophagus,  injection 
of  an  emetic  caused  a  typical  vomiting  movement  with  ejection  of 

""Archiv  f.  die  gesammte  Physiologie,"  8,  160,  1874;  63,  362,  1896. 


742  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

the  contents  of  the  bladder.  Gianuzzi  showed,  on  the  other  hand, 
that  upon  a  curarized  animal  vomiting  could  not  be  produced  by  an 
emetic — because,  apparently,  the  muscles  of  the  abdomen  were 
paralyzed  by  the  curare.  There  are  on  record  a  number  of  ob- 
servations which  tend  to  show  that  the  stomach  is  not  passive 
during  the  act.  On  the  contrary,  it  may  exhibit  contractions,  more 
or  less  violent  in  character.  According  to  Openchowski,*  the 
pylorus  is  closed  and  the  pyloric  end  of  the  stomach  firmly  con- 
tracted so  as  to  drive  the  contents  toward  the  dilated  cardiac  por- 
tion. Cannon  states  that  in  cats  the  normal  peristaltic  waves  pass 
over  the  pyloric  portion  in  the  period  preceding  the  vomiting  and 
that  finally  a  strong  contraction  at  the  "transverse  band"  com- 
pletely shuts  off  the  pyloric  portion  from  the  body  of  the  stomach, 
which  at  this  time  is  quite  relaxed.  The  act  of  vomiting  is,  in  fact, 
a  complex  reflex  movement  into  which  many  muscles  enter.  The 
following  events  are  described :  The  vomiting  is  usually  preceded  by 
a  sensation  of  nausea  and  a  reflex  flow  of  saliva  into  the  mouth. 
These  phenomena  are  succeeded  or  accompanied  by  retching  mmm. 
ments,  which  consist  essentially  in  deep,  spasmodic  inspirations  with 
a  closed  glottis.  The  effect  of  these  movements  is  to  compress  the 
stomach  by  the  descent  of  the  diaphragm,  and  at  the  same  time  to 
increase  decidedly  the  negative  pressure  in  the  thorax,  and  therefore 
in  the  thoracic  portion  of  the  esophagus.  During  one  of  these 
retching  movements  the  act  of  vomiting  is  effected  by  a  convulsive 
contraction  of  the  abdominal  wall  that  exerts  a  sudden  additional 
strong  pressure  upon  the  stomach.  At  the  same  time  the  cardiac 
orifice  of  the  stomach  is  dilated,  probably  by  an  inhibition  of  the 
sphincter,  and  according  to  the  above  description  the  fundic  end 
of  the  stomach  is  also  dilated,  while  the  pyloric  end  is  in  strong 
contraction.  The  stomach  contents  are,  therefore,  forced  vio- 
lently out  of  the  stomach  through  the  esophagus,  the  negative 
pressure  in  the  latter  probably  assisting  in  the  act.  The  passage 
through  the  esophagus  is  effected  mainly  by  the  force  of  the  con- 
traction of  the  abdominal  muscles;  there  is  no  evidence  of  anti- 
peristaltic  movements  on  the  part  of  the  esophagus  itself.  Dur- 
ing the  ejection  of  the  contents  of  the  stomach  the  glottis  is  kept 
closed  by  the  adductor  muscles,  and  usually  the  nasal  chamber  is 
likewise  shut  off  from  the  pharynx  by  the  contraction  of  the 
posterior  pillars  of  the  fauces  on  the  palate  and  uvula.  In  violent 
vomiting,  however,  the  vomited  material  may  break  through 
this  latter  barrier  and  be  ejected  partially  through  the  nose. 

Nervous  Mechanism  of  Vomiting. — That  vomiting  is  a  reflex  act 
is  abundantly  shown  by  the  frequency  with  which  it  is  produced  in 
consequence  of  the  stimulation  of  sensory  nerves  or  as  the  result 

*  Openchowski,  "Archiv  f.  Physiologie,"  1899,  p.  552. 


MOVEMENTS    OF    THE    ALIMENTARY    CANAL.  743 

of  injuries  to  various  parts  of  the  central  nervous  system.  After 
lesions  or  injuries  of  the  brain  vomiting  often  results.  Disagreeable 
emotions  and  disturbances  of  the  sense  of  equilibrium  may  produce 
the  same  result.  Irritation  of  the  mucous  membrane  of  various 
parts  of  the  alimentary  canal  (as,  for  example,  tickling  the  back 
of  the  pharynx  with  the  finger);  disturbances  of  the  urogenital 
apparatus,  the  liver,  and  other  visceral  organs;  artificial  stimula- 
tion of  the  trunk  of  the  vagus  and  of  other  sensory  nerves,  may  all 
cause  vomiting.  Under  ordinary  conditions,  however,  irritation  of 
the  sensory  nerves  of  the  gastric  mucous  membrane  is  the  most 
common  cause  of  vomiting.  This  effect  may  result  from  the  prod- 
ucts of  fermentation  in  the  stomach  in  cases  of  indigestion,  or  may 
be  produced  intentionally  by  local  emetics,  such  as  mustard,  taken 
into  the  stomach.  The  afferent  path  in  this  case  is  through  the 
sensory  fibers  of  the  vagus.  The  efferent  paths  of  the  reflex  are 
found  in  the  motor  nerves  innervating  the  muscles  concerned  in  the 
vomiting, — namely,  the  vagus,  the  phrenics,  and  the  spinal  nerves 
supplying  the  abdominal  muscles.  Whether  or  not  there  is  a  defi- 
nite vomiting  center  in  which  the  afferent  impulses  are  received 
and  through  which  a  co-ordinated  series  of  efferent  impulses  is 
sent  out  to  the  various  muscles  has  not  been  satisfactorily  deter- 
mined. It  has  been  shown  that  the  portion  of  the  nervous  system 
through  which  the  reflex  is  effected  lies  in  the  medulla,  and  it  may 
be  observed  that  the  muscles  concerned  in  the  act,  outside  those 
of  the  stomach,  are  respiratory  muscles.  Vomiting,  in  fact,  consists 
essentially  in  a  simultaneous  spasmodic  contraction  of  expiratory 
(abdominal)  muscles  and  inspiratory  muscles  (diaphragm).  It  has 
therefore  been  suggested  that  the  reflex  involves  the  stimulation  of 
the  respiratory  center  or  some  part  of  it.  Thumas  claims  to  have 
located  a  vomiting  center  in  the  medulla  in  the  immediate  neighbor- 
hood of  the  calamus  scrip torius.  Further  evidence,  however,  is 
required  upon  this  point.  The  act  of  vomiting  may  be  produced 
not  only  as  a  reflex  from  various  sensory  nerves,  but  may  also  be 
caused  by  direct  action  upon  the  medullary  centers.  The  action 
of  apomorphin  is  most  easily  explained  by  supposing  that  it  acts 
directly  on  the  nerve  centers. 


CHAPTER  XL. 

GENERAL  CONSIDERATIONS  UPON  THE  COMPOSITION 
OF  THE  FOOD  AND  THE  ACTION  OF  ENZYMES. 

Foods  and  Foodstuffs.  —  The  term  food  when  used  in  a  popular 
sense  includes  everything  that  we  eat  for  the  purpose  of  nourishing 
the  body.  From  this  point  of  view  the  food  of  mankind  is  of  a  most 
varied  character,  comprising  a  great  variety  of  products  of  the 
animal  and  vegetable  kingdoms.  Chemical  analysis  of  the  animal 
and  vegetable  foods  shows,  however,  that  they  all  contain  one  or 
more  of  five  different  classes  of  substances  which  are  usually 
designated  as  the  foodstuffs  (older  names,  alimentary  or  proximate 
principles)  on  the  belief  that  they  form  the  useful  constituent  of  our 
foods.  The  classification  of  foodstuffs  usually  given  is  as  follows: 

r  Water. 

Inorganic  salts. 
Foodstuffs  <  Proteins. 

Carbohydrates. 


From  the  scientific  point  of  view,  a  foodstuff  or  food  may  be  defined 
as  a  substance  absolutely  necessary  to  the  normal  composition  of 
the  body,  as  in  the  case  of  water  and  salts,  or  as  a  substance  which 
can  be  acted  upon  by  the  tissues  of  the  body  in  such  a  way  as  to 
yield  energy  (heat,  for  example)  or  to  furnish  material  for  the  pro- 
duction or  repair  of  living  tissue.  Moreover,  to  be  a  food  in  the 
physiological  sense,  the  substance  must  not  directly  or  indirectly 
affect  injuriously  the  normal  nutritive  processes  of  the  tissues. 
The  five  substances  named  above  are  all  foods  in  this  sense.  The 
water  and  certain  salts  of  sodium,  potassium,  calcium,  mag- 
nesium, iron,  and  perhaps  other  elements  are  absolutely  necessary 
to  maintain  the  normal  composition  of  the  tissue.  Complete 
withdrawal  of  any  one  of  these  constituents  would  cause  the  death 
of  the  organism.  Proteins,  fats,  and  carbohydrates,  on  the  other 
hand,  are  substances  whose  molecules  have  a  more  or  less  com- 
plex structure.  When  eaten  and  digested  they  enter  the  body 
liquids,  and  are  employed  either  in  the  synthesis  of  the  more  com- 
plex living  matter  or  they  undergo  various  chemical  changes,  spoken 
of  in  general  as  metabolism,  which  result  finally  in  the  breaking  up 
of  their  complex  molecules  with  a  liberation  of  some  of  their  internal 

744 


COMPOSITION    OF    FOOD    AND    ACTION    OF    ENZYMES. 


745 


energy.  The  chemical  changes  of  metabolism  or  nutrition  are, 
in  the  long  run,  mainly  exothermic, — that  is,  they  are  attended 
by  the  production  of  heat.  Some  of  the  chemical  or  internal  energy 
that  held  the  complex  molecules  together  assumes  the  form  of  heat 
when  these  molecules  are  broken  down  by  oxidative  changes  to  sim- 
pler, more  stable  structures,  such  as  water,  carbon  dioxid,  and  urea. 
Proteins,  fats,  and  carbohydrates  form  materials  that  the  tissue 
cells  are  adjusted  to  act  upon  after  they  have  undergone  certain 
changes  during  digestion.  Other  complex  organic  compounds  con- 
taining chemical  energy  are  either  injurious  to  the  tissues,  or  they 
have  a  structure  such  that  the  tissues  cannot  act  upon  them. 
Such  substances  cannot  be  considered  as  foods  in  the  scientific 
sense.  When,  therefore,  we  desire  to  know  the  food  value  of  any 
animal  or  vegetable  product,  we  analyze  it  to  determine  its  compo- 
sition as  regards  water,  salts,  proteins,  fats,  and  carbohydrates. 
The  following  table  compiled  by  Munk  from  the  analyses  given  by 
Konig  *  may  be  taken  as  an  indication  of  the  average  composition 

of  the  most  commonly  used  foods: 

\ 

COMPOSITION  OF  FOODS. 


CARBOHY 

DRATE. 

IN  100  PARTS. 

WATER. 

PROTEIM. 

FAT. 

DIGESTIBLE. 

CELLULOSE. 

ASH. 

Meat  

76  7 

208 

1.5 

03 

1  3 

EfiTCS 

73  7 

126 

12.1 

1  1 

i^pe     

Cheese       

36-60 

25-33 

7-30 

3-7 

3  4 

Cows'  milk  

87.7 

34 

3.2 

48 

07 

Human  milk  

89.7 

20 

3.1 

50 

02 

Wheat  flour  

13.3 

102 

0.9 

748 

03 

05 

Wheat  bread  
Rye  flour  

35.6 
13.7 

7.1 
11.5 

0.2 
2.1 

55.5 
697 

0.3 
1  6 

.1 
4 

42.3 

6.1 

0.4 

49.2 

05 

5 

Rice  

13.1 

7.0 

0.9 

77.4 

06 

o 

Corn  

13.1 

9.9 

4.6 

68.4 

2.5 

5 

Macaroni 

10  1 

9  0 

03 

79  0 

03 

05 

Peas,  beans,  lentils 
Potatoes  

12-15 
755 

23-26 
20 

l*-2 
02 

49-54 
206 

4-7 
07 

2-3 

1  0 

Carrots  

87  1 

1  0 

02 

93 

14 

09 

Cabbages  

90 

2-3 

05 

4-6 

1-2 

1  3 

Mushrooms  

73-91 

4-8 

05 

3-12 

1-5 

1  2 

Fruit    . 

84 

0.5 

10 

4 

0.5 

An  examination  of  this  table  shows  that  the  animal  foods,  par- 
ticularly the  meats,  are  characterized  by  their  small  percentage  in 
carbohydrate  and  by  a  relatively  large  amount  of  protein  or  of 
protein  and  fat.  With  regard  to  the  last  two  foodstuffs,  meats  differ 

*See  Konig,  "Die  menschlichen  Nahrungs  und  Genussmittel ";  and 
Atwater  and  Bryant,  "  The  Chemical  Composition  of  American  Food  Mate- 
rials," Bulletin  28,  United  States  Department  of  Agriculture,  1899. 


746 


PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 


very  much  among  themselves.  Some  idea  of  the  limits  of  variation 
may  be  obtained  from  the  following  table,  taken  chiefly  from 
Konig's  analyses: 


WATER. 

PROTEIN. 

FAT. 

CARBOHYDRATE. 

ASH. 

Beef,  moderately  fat  .... 
Veal  fat  .  ... 

73.03 
7231 

20.96 

1888 

5.41 

741 

046 
007 

1.14 
1  33 

Mutton,  moderately  fat  .  . 
Pork,  lean  

75.99 
7257 

17.11 
2005 

5.77 
6.81 

1.33 
1.10 

Ham  salted  

6258 

2232 

8.68 

6.42 

Pork  (bacon),  very  fat*  . 
Mackerel*  

10.00 
71.6 

3.00 

18.8 

80.50 
8.2 

6.5 
1.4 

The  vegetable  foods  are  distinguished,  as  a  rule,  by  their  large 
percentage  in  carbohydrates  and  the  relatively  small  amounts  of 
proteins  and  fats,  as  seen,  for  example,  in  the  composition  of  rice, 
corn,  wheat,  and  potatoes.  Nevertheless,  it  will  be  noticed  that  the 
proportion  of  protein  in  some  of  the  vegetables  is  not  at  all  insignifi- 
cant. They  are  characterized  by  their  excess  in  carbohydrates 
rather  than  by  a  deficiency  in  proteins.  The  composition  of  peas 
and  other  leguminous  foods  is  remarkable  for  the  large  percentage 
of  protein,  which  exceeds  that  found  in  meats.  Analyses  such  as 
are  given  here  are  indispensable  in  determining  the  true  nutritive 
value  of  foods.  Nevertheless,  it  must  be  borne  in  mind  that  the 
chemical  composition  of  a  food  is  not  alone  sufficient  to  determine 
its  precise  value  in  nutrition.  It  is  obviously  true  that  it  is  not  what 
we  eat,  but  what  we  digest  and  absorb,  that  is  nutritious  to  the 
body;  so  that,  in  addition  to  determining  the  proportion  of  food- 
stuffs in  any  given  food,  it  is  necessary  to  determine  to  what  extent 
the  several  constituents  are  digested.  This  factor  can  be  obtained 
only  by  actual  experiments.  It  may  be  said  here,  however,  that 
in  general  the  proteins  of  animal  foods  are  more  completely  digested 
than  are  those  of  vegetables,  owing  chiefly  to  the  fact  that  the 
latter  may  contain  a  considerable  amount  of  indigestible  cellulose, 
which  tends  to  protect  the  protein  from  the  action  of  the  diges- 
tive secretions.  In  the  animal  foods,  therefore,  chemical  analysis 
comes  nearer  to  expressing  directly  the  nutritive  value. 

It  must  be  borne  in  mind  also,  as  will  be  explained  more  in 
detail  in  the  chapters  on  nutrition,  that  our  various  foods,  animal 
and  vegetable,  may  contain  substances  other  than  the  proteins, 
fats,  and  carbohydrates,  which  play  an  accessory  or  even  essential 
role  in  the  complex  chemical  processes  of  nutrition.  This  idea  is 
illustrated  by  the  existence  of  what  are  known  as  food  accessories  or 
viiamines  (p.  912),  and  their  mysteriously  important  relation  to 
normal  nutrition.  The  proteins  also,  it  will  be  found,  are  not  all  of 
equal  value  in  metabolism,  and  the  same  fact  is  true  probably  to 
*  Atwater,  "The  Chemistry  of  Foods  and  Nutrition,"  1887. 


COMPOSITION    OF    FOOD    AND    ACTION    OF    ENZYMES.  747 

some  extent  for  the  different  fats  and  carbohydrates.  The  matter 
is  referred  to  here  only  to  emphasize  the  point  that  an  analysis  giv- 
ing the  percentage  of  protein,  fat,  carbohydrate,  ash,  and  water 
does  not  in  itself  reveal  the  complete  nutritive  importance  of  a 
food.  There  is  much  to  be  learned  regarding  the  specific  action  of 
the  many  varieties  of  food-stuffs  which,  at  present,  cannot  be  stated 
in  a  table  of  analyses  of  the  foods. 

Accessory  Articles  of  Diet. — In  addition  to  the  foodstuffs 
proper,  our  foods  contain  numerous  other  substances  which  in 
one  way  or  another  are  useful  in  nutrition,  although  not  abso- 
lutely necessary.  These  substances,  differing  in  nature  and 
importance,  may  be  classified  under  the  three  heads  of: 

Flavors:   The  various  oils  or  esters  that  give  odor  and  taste  to  foods. 
Condiments:   Pepper,  salt,  mustard,  etc. 
Stimulants:   Alcohol,  tea,  coffee,  cocoa,  etc. 

The  specific  influence  of  these  substances  in  digestion  and  nutri- 
tion is  considered  in  the  section  on  Nutrition. 

The  Chemical  Changes  of  the  Foodstuffs  during  Digestion. 
— The  physiology  of  digestion  consists  chiefly  in  the  study  of  the 
chemical  changes  that  the  food  undergoes  during  its  passage  through 
the  alimentary  canal.  It  happens  that  these  chemical  changes  are 
of  a  peculiar  character.  The  peculiarity  is  due  to  the  fact  that  the 
changes  of  digestion  are  effected  through  the  agency  of  a  group  of 
bodies  known  as  enzymes,  or  unorganized  ferments,  whose  chemical 
action  is  more  obscure  than  that  of  the  ordinary  reagents  with  which 
we  have  to  deal.  It  will  save  repetition  to  give  here  certain  general 
facts  that  are  known  with  reference  to  these  bodies,  reserving  for 
later  treatment  the  details  of  the  action  of  the  specific  enzymes 
found  in  the  different  digestive  secretions. 


ENZYMES  AND  THEIR  ACTION. 

Historical. — The  term  fermentation  and  the  idea  that  it  is 
meant  to  convey  has  varied  greatly  during  the  course  of  years.  The 
word  at  first  was  applied  to  certain  obvious  and  apparently  spon- 
taneous changes  in  organic  materials  which  are  accompanied  by  the 
liberation  of  bubbles  of  gas:  such,  for  instance,  as  the  alcoholic 
fermentations,  in  which  alcohol  is  formed  from  sugar;  the  acid  fer- 
mentations, as  in  the  souring  of  milk;  and  the  putrefactive  fer- 
mentations, by  means  of  which  animal  substances  are  disintegrated, 
with  the  production  of  offensive  odors.  These  mysterious  phenom- 
ena excited  naturally  the  interest  of  investigators,  and  with  the 
development  of  chemical  knowledge  numerous  other  processes  were 
discovered  which  resemble  the  typical  fermentations  in  that  they 
seem  to  be  due  to  specific  agents  whose  mode  of  action  differs  from 
the  usual  chemical  reactions,  especially  in  the  fact  that  the  causa- 


748  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

live  agent  itself,  or  the  ferment  as  it  is  called,  is  not  destroyed  or 
used  up  in  the  reaction.  Thus  it  was  discovered  that  germinating 
barley  grains  contain  a  something  which  can  be  extracted  by  water 
and  which  can  convert  starch  into  sugar  (Kirchhoff,  1814).  Later 
this  substance  was  separated  by  precipitation  with  alcohol  and  was 
given  the  name  of  diastase  (Payen  and  Persoz,  1833).  Schwann 
in  1836  demonstrated  the  existence  of  a  ferment  (pepsin)  in  gastric 
juice  capable  of  acting  upon  albuminous  substances,  and  a  number 
of  similar  bodies  were  soon  discovered:  trypsin  in  the  pancreatic 
juice,  amygdalin,  invertin,  ptyalin,  etc.  These  substances  were  all 
designated  as  ferments,  and  their  action  was  compared  to  that  of 
the  alcoholic  fermentation  in  yeast,  the  process  of  putrefaction,  etc. 
Naturally  very  many  theories  have  been  proposed  regarding  the 
cause  of  the  processes  of  fermentation.  For  the  historical  develop- 
ment and  interrelation  of  these  theories  references  must  be  made  to 
special  works.*  It  is  sufficient  here  to  say  that  the  brilliant  work 
of  Pasteur  established  the  fact  that  the  fermentations  in  the  old 
sense — alcoholic,  acid,  and  putrefactive — are  due  to  the  presence 
and  activity  of  living  organisms.  He  showed,  moreover,  that 
many  diseases  are  likewise  due  to  the  activity  of  minute  living 
organisms,  and  thus  justified  the  view  held  by  some  of  the  older 
physicians  that  there  is  a  close  similarity  in  the  processes  of  fer- 
mentation and  disease.  .  The  clear  demonstration  of  the  importance 
of  living  organisms  in  some  fermentations  and  the  equally  clear 
proof  of  the  existence  of  another  group  of  ferment  actions  in  which 
living  material  is  not  directly  concerned  led  to  a  classification  which 
is  used  even  at  the  present  day.  This  classification  divided  fer- 
ments into  two  great  groups :  the  living  or  organized  ferments,  such 
as  the  yeast  cell,  bacteria,  etc.;  and  the  non-living  or  unorganized 
ferments,  such  as  pepsin,  trypsin,  etc.,  which  later  were  generally 
designated  as  enzymes  (Kuhne).  The  separation  appeared  to  be 
entirely  satisfactory  until  Buchner  (1897)  showed  that  an  unor- 
ganized ferment,  an  enzyme  (zymase)  capable  of  producing  alcohol 
from  sugar,  may  be  extracted  from  yeast  cells.  Later  the  same 
observer  (1903)  succeeded  in  extracting  enzymes  from  the  lactic- 
acid-producing  bacteria  and  the  acetic-acid-producing  bacteria 
which  are  capable  of  giving  the  same  reactions  as  the  living  bacteria. 
These  discoveries  indicate  clearly  that  there  is  no  essential  difference 
between  the  activity  of  living  and  non-living  ferments.  The  so- 
called  organized  ferments  probably  produce  their  effects  not  by 
virtue  of  their  specific  life-metabolism,  but  in  part,  at  least,  by  the 
manufacture  within  their  substance  of  specific  enzymes.  If  we  can 

*  Consult  Oppenheimer,  "Die  Fennente  und  ihre  Wirkungen,"  second 
edition,  1903;  Moore,  in  "Recent  Advances  in  Physiology  and  Biochemistry," 
London  and  New  York,  1906;  Vernon,  " Intracellular  Enzymes,"  London, 
1908;  Euler,  "General  Chemistry  of  the  Enzymes"  (translation  by  Pope),  1912. 


COMPOSITION    OF    FOOD    AND    ACTION    OF    ENZYMES.  749 

accept  this  conclusion,  then  the  general  explanation  of  fermentation 
is  to  be  sought  in  the  nature  of  the  enzymatic  processes.  Within  re- 
cent years  the  study  of  the  enzymes  has  attracted  especial  attention. 
The  general  point  of  view  regarding  their  mode  of  action  that  is 
most  frequently  met  with  to-day  is  that  advocated  especially 
by  Ostwald.  He  assumes,  reviving  an  older  view  (Berzelius), 
that  the  ferment  actions  are  similar  to  those  of  catalysis.  By 
catalysis  chemists  designated  a  species  of  reaction  which  is  brought 
about  by  the  mere  contact  or  presence  of  certain  substances,  the 
catalyzers.  Thus,  hydrogen  a;nd  oxygen  at  ordinary  temperatures 
do  not  combine  to  form  water,  but  if  spongy  platinum  is  present 
the  two  gases  unite  readily.  The  platinum  does  not  enter  into  the 
reaction,  at  least  it  undergoes  no  change,  and  it  is  said,  therefore, 
to  act  by  catalysis.  Many  similar  catalytic  reactions  are  known, 
and  the  chemists  have  reached  the  important  generalization  that 
in  such  reactions  the  catalyzer,  platinum  in  the  above  instance, 
simply  hastens  a  process  which  would  occur  without  it,  but  much 
more  slowly.  A  catalyzer  is  a  substance,  therefore,  that  alters 
the  velocity  of  a  reaction,  but  does  not  initiate  it.  This  idea  is 
illustrated  very  clearly  by  the  catalysis  of  hydrogen  peroxid.  This 
substance  decomposes  spontaneously  into  water  and  oxygen  accord- 
ing to  the  reaction  H2O2  =  H2O  -{-  O,  but  the  decomposition  is 
greatly  hastened  by  the  presence  of  a  catalyzer.  Thus,  Bredig  has 
shown  that  platinum  in  very  fine  suspension,  so-called  colloidal 
solution,  exerts  a  marked  accelerating  influence  upon  this  reaction; 
one  part  of  the  colloidal  platinum  to  350  million  parts  of  water 
may  still  exercise  a  perceptible  effect.  The  blood  and  aqueous  ex- 
tracts of  various  tissues  also  catalyze  the  hydrogen  peroxid  readily, 
and  this  effect  has  been  attributed  to  the  action  of  an  enzyme  (cata- 
lase).  The  view  has  been  proposed,  therefore,  that  the  enzymes  of 
the  body  act  like  the  catalyzers  of  inorganic  origin:  they  influence 
the  velocity  of  certain  special  reactions.  Such  a  general  conception 
as  this  unifies  the  whole  subject  of  fermentation  and  holds  out  the 
hope  that  the  more  precise  investigations  that  are  possible  in  the  case 
of  the  inorganic  catalyzers  will  eventually  lead  to  a  better  under- 
standing of  the  underlying  physical  causes  of  fermentation.  It 
should  be  borne  in  mind,  however,  that  some  of  the  best  known  of  the 
ferment  actions  of  the  body,  such  as  the  peptic  or  tryptic  digestion  of 
protein,  fit  into  this  view  only  theoretically  and  by  analogy.  As  a 
matter  of  fact,  albumins  at  ordinary  temperatures  do  not  split  up 
spontaneously  into  the  products  formed  by  the  action  of  pepsin; 
if  we  consider  that  the  pepsin  simply  accelerates  a  reaction  already 
taking  place,  it  must  be  stated  that  this  reaction  at  ordinary 
temperatures  is  infinitely  slow, — that  is,  practically  does  not  occur. 
At  higher  temperatures,,  however,  similar  decompositions  of  al- 
bumin may  be  obtained  without  the  presence  of  an  enzyme. 


750  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

Reversible  Reactions. — It  has  been  shown  that  under  proper 
conditions  many  chemical  reactions  are  reversible, — that  is,  may 
take  place  in  opposite  directions.  For  instance,  acetic  acid  and 
ethyl-alcohol  brought  together  react  with  the  production  of  ethyl- 
acetate  and  water: 

CH3COOH  +  C2H6OH  =  CH3COOC2H6  +  H2O. 

Acetic  acid.          Alcohol.  Ethyl-acetate.        Water. 

On  the  other  hand,  when  ethyl-acetate  and  water  are  brought 
together  they  react  with  the  formation  of  some  acetic  acid  and 
ethyl-alcohol,  so  that  the  reaction  indicated  in  the  above  equation 
takes  place  in  opposite  directions,  figuratively  speaking, — a  fact 
which  may  be  indicated  by  a  symbol  of  this  kind: 

CH3COOH  +  C2H6OH  ^±  CH3COOC2H6  +  H2O. 

It  is  evident  that  in  a  reversible  reaction  of  this  sort  the  opposite 
changes  will  eventually  strike  an  equilibrium,  the  solution  or  mix- 
ture will  contain  some  of  all  four  substances,  and  this  equilib- 
rium will  remain  constant  as  long  as  the  conditions  are  unchanged. 
If  the  conditions  are  altered,  however, — if,  for  example,  some  of  the 
substances  formed  are  removed  or  the  mixture  is  altered  as  to  its 
concentration, — then  the  reaction  will  proceed  unequally  in  the  two 
directions  until  a  new  equilibrium  is  established.  The  importance, 
in  the  present  connection,  of  this  conception  of  reversibility  of  reac- 
tions is  found  in  the  fact  that  a  number  of  the  catalytic  reactions 
are  also  reversible.  The  catalyzer  may  not  only  accelerate  a  reac- 
tion between  two  substances,  but  may  also  accelerate  the  recom- 
position  of  the  products  into  the  original  substances.  An  excellent 
instance  of  this  double  effect  has  been  obtained  by  Kastle  and 
Loevenhart  in  experiments  upon  one  of  the  enzymes  of  the  animal 
body,  lipase.  Lipase  is  the  enzyme  which  in  the  body  acts  upon  the 
neutral  fats,  converting  them  into  fatty  acids  and  glycerin, — a 
process  that  takes  place  as  a  usual  if  not  necessary  step  in  the  diges- 
tion and  absorption  of  fats.  The  authors  above  named*  made  use 
of  a  simple  ester  analogous  to  the  fats,  ethyl-butyrate,  and  showed 
that  lipase  causes  not  9nly  an  hydrolysis  of  this  substance  into  ethyl- 
alcohol  and  butyric  acid,  but  also  a  synthesis  of  the  two  last-named 
substances  into  ethyl-butyrate  and  water.  The  reaction  effected 
by  the  lipase  is  therefore  reversible  and  may  be  expressed  as: 

C3H7COOC2H6  +  H20  ^±  C3H7COOH  +  C2HSOH. 

Ethyl-butyrate.      Water.  Butyric  acid.     Ethyl-alcohol. 

Lipase  is  capable  of  exerting  probably  a  similar  reversible  reaction  on 
the  fats  in  the  body.  Assuming  the  existence  of  such  an  action  in 
the  body,  it  is  possible  to  explain  not  only  the  digestion  of  fats,  but 

*  Kastle  and  Loevenhart,  "  American  Chemical  Journal,"  24,  491,  1900. 
See  also  Loevenhart,  "American  Physiological  Journal,"  6,  331,  1902. 


COMPOSITION    OF    FOOD    AND    ACTION    OF    ENZYMES.  751 

also  their  formation  in  the  tissues  and  their  absorption  from  the 
tissues  during  starvation.  That  is,  according  to  the  conditions  of 
concentration,  etc.,  one  and  the  same  enzyme  may  cause  a  splitting 
up  of  the  neutral  fat  into  fatty  acids  and  glycerin  or  a  storing  up  of 
neutral  fat  by  the  synthesis  of  fatty  acid  and  glycerin.  In  the  sub- 
cutaneous tissues,  therefore,  fat  may  be  stored,  to  a  certain  point, 
or,  if  the  conditions  are  altered,  the  fat  that  is  there  may  be  changed 
over  to  the  fatty  acids  and  glycerin  and  be  oxidized  in  the  body  as 
food. 

A  similar  reversibility  has  been  shown  for  some  of  the  other 
enzymes  of  the  body  (maltase  by  Hill,  1898),  but  whether  or  not  all 
of  them  will  be  shown  to  possess  this  power  under  the  conditions  of 
temperature,  etc.,  that  prevail  in  the  body  can  only  be  determined 
by  actual  experiments. 

The  Specificity  of  Enzymes. — A  most  interesting  feature  of 
the  activity  of  enzymes  is  that  it  is  specific.  The  enzymes  that 
act  upon  the  carbohydrates  are  not  capable  of  affecting  the  pro- 
teins or  fats,  and  vice  versa.  So  in  the  fermentation  of  closely 
related  bodies  such  as  the  double  sugars,  the  enzyme  that  acts 
upon  the  maltose  is  not  capable  of  affecting  the  lactose;  each  re- 
quires seemingly  its  own  specific  enzyme.  In  fact,  there  is  no  clear 
proof  that  any  single  enzyme  can  produce  more  than  one  kind  of 
ferment  action.  If  in  any  extract  or  secretion  two  or  more  kinds 
of  ferment  action  can  be  demonstrated,  the  tendency  at  present 
is  to  attribute  these  different  activities  to  the  existence  of  separate 
and  specific  enzymes.  The  pancreatic  juice,  for  example,  splits 
proteins,  starches,  and  fats  and  curdles  milk,  and  there  are  assumed 
to  be  four  different  enzymes  present, — namely,  trypsin,  diastase, 
lipase,  and  rennin.  So  if  an  extract  containing  diastase  is  also 
capable  of  decomposing  hydrogen  peroxid  it  is  believed  that  this 
latter  effect  is  due  to  the  existence  of  a  special  enzyme,  catalase. 
It  seems  quite  probable  that  this  specificity  of  the  different  enzymes 
may  be  related,  as  Fischer*  has  suggested,  to  the  geometrical  struc- 
ture of  the  substance  acted  upon.  Each  ferment  is  adapted  to  act 
upon  or  become  attached  to  a  molecule  with  a  certain  definite 
structure, — fitted  to  it,  in  fact,  as  a  key  to  its  lock.  In  this  respect 
the  action  of  the  so-called  hydrolytic  enzymes  differs  markedly  from 
the  dilute  acids  or  alkalies  which  hydrolyze  many  different  substances 
without  indication  of  any  specificity.  Attention  has  been  called  to 
the  fact  that  this  adaptibility  of  enzymes  to  certain  specific  struc- 
tures in  the  molecules  acted  upon  resembles  closely  the  specific 
activity  of  the  toxins,  and  many  useful  and  suggestive  com- 
parisons may  be  drawn  between  the  mode  of  action  of  enzymes 
and  toxins.  It  has  become  customary  to  speak  of  the  substance 

*  Fischer,  "Zeitschrift  f.  physiolog.  Chemie,"  26,  71,  1898. 


752  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

upon  which  an  enzyme  acts  as  its  substrate,  and  it  has  been 
assumed  that  the  action  of  the  enzyme,  like  that  of  the  toxins, 
takes  place  in  two  stages;  first,  the  combination  of  the  enzyme 
and  the  substrate;  second,  the  breaking  down  of  this  compound 
to  give  the  final  products  of  the  reaction.  There  is  some  reason 
for  believing  that  these  two  stages  may  be  separated,  and  that 
enzymes  which  on  account  of  certain  conditions,  such  as  heating, 
have  lost  their  power  of  decomposing  the  substrate,  may  still 
have  the  power  of  combining  with  it.  Toxins  showing  a  similar 
property  are  designated  as  toxoids,  and  for  the  enzyme  in  this 
condition  the  term  zymoid  has  been  suggested  (Bayliss) 

Definition  and  Classification  of  Enzymes  (Ferments) . — On  the 
basis  of  the  considerations  presented  in  the  preceding  paragraphs 
Oppenheimer  suggests  the  following  definition:  An  enzyme  is  a 
substance,  produced  by  living  cells,  which  acts  by  catalysis.  The 
enzyme  itself  remains  unchanged  in  this-  process,  and  it  acts  specifi- 
cally,— that  is,  each  enzyme  exerts  its  activity  only  upon  substances 
whose  molecules  have  a  certain  definite  structural  and  stereochemi- 
cal  arrangement.  The  enzymes  of  the  body  are  organic  substances 
of  a  colloid  structure  whose  chemical  composition  is  unknown. 
A  distinction  is  made  frequently  between  endo-enzymes  and  exo- 
enzymes.  Under  the  latter  group  are  included  those  enzymes  which 
are  eliminated  from  the  cells  in  which  they  are  formed,  and  which 
are  found,  therefore,  in  solution  in  the  secretions,  for  example, 
the  ptyalin  of  the  saliva  or  the  pepsin  of  the  gastric  juice.  By 
endo-enzymes  is  meant  a  group  of  intracellular  enzymes  which  are 
not  secreted,  but  are  held  within  the  cells  in  some  form  of  com- 
bination. To  obtain  them  in  solution  or  suspension  it  is  necessary 
to  destroy  this  cell,  usually  by  mechanical  means,  such  as  grinding 
the  tissue  with  sand  and,  in  some  cases,  by  submitting  the  ground 
mass  to  a  great  pressure  in  a  hydraulic  press.  The  liquid  obtained 
by  this  latter  method  is  known  as  the  "  press  juice  "  of  the  tissue. 
In  life  the  endo-enzymes  play  their  part  within  the  bounds  of  the 
cells  in  which  they  are  contained,  and  probably  constitute  the 
chief  means  through  which  are  effected  the  metabolic  processes 
that  characterize  living  matter. 

With  regard  to  the  names  and  classification  of  the  different 
enzymes,  much  difficulty  is  experienced.  There  is  no  consensus 
among  workers  as  to  the  system  to  be  followed.  Duclaux  has  sug- 
gested that  an  enzyme  be  designated  by  the  name  of  the  body  on 
which  its  action  is  exerted,  and  that  all  of  them  be  given  the  termin- 
ation -ase.  The  enzyme  acting  on  fat  on  this  system  would  be 
named  lipase;  that  on  starch,  amylase;  that  on  maltose,  maltase, 
etc.  The  suggestion  has  been  followed  in  part  only,  the  older  en- 
zymes which  were  first  discovered  being  referred  to  most  frequently 
under  their  original  names.  Having  in  mind  only  the  needs  of 


COMPOSITION    OF    FOOD    AND    ACTION    OF    ENZYMES.  753 

animal  physiology,  the  following  classification  will  be  used  in  the 
treatment  of  the  subjects  of  digestion  and  nutrition: 

1.  The  proteolytic  or  protein-splitting  enzymes.     Examples:  Pepsin  of  gastric 

juice,  trypsin  of  pancreatic  juice.  They  cause  a  hydrolytic  cleavage  of 
the  protein  molecule. 

2.  The  amylolytic  or  starch-splitting  enzymes.     Examples:    Ptyalin  or  sali- 

vary diastase,  amylase,  or  pancreatic  diastase.  Their  action  is  closely 
similar  to  that  of  the  classical  enzyme  of  this  groups-diastase — found 
in  germinating  barley  grains.  They  cause  a  hydrolytic  cleavage  of  the 
starch  molecule. 

3.  The-  lipolytic,  or  fat-splitting  enzymes.     Example:     The  lipase  found  in 

the  pancreatic  secretion,  in  the  liver,  connective  tissues,  blood,  etc. 
They  cause  a  hydrolytic  cleavage  of  the  fat  molecule. 

4.  The  sugar-splitting  enzymes.     These  again  fall  into  two  subgroups:     (a) 

The  inverting  enzymes,  which  convert  the  double  sugars  or  disaccharids 
into  the  monosaccharids.  Examples:  Maltase,  which  splits  maltose  to 
dextrose;  invertase,  which  splits  cane-sugar  to  dextrose  and  levulose; 
and  lactase,  which  splits  milk-sugar  (lactose)  to  dextrose  and  galactose. 
(6)  The  enzymes,  which  split  the  monosaccharids.  There  is  evidence  of 
the  presence  in  the  tissues  of  an  enzyme  or  enzymes  capable  of  splitting 
the  sugar  of  the  blood  and  tissues  (dextrose)  into  lactic  acid. 

5.  The  coagulating  enzymes,  which  convert  soluble  to  insoluble  proteins. 

Example:    The  coagulation  of  the  casein  of  milk  by  rennin. 

6.  The  oxidizing  enzymes,  or  oxidases.     A  group  of  enzymes  which  set  up 

oxidation  processes.  Some  of  the  details  of  the  activity  of  these  enzymes 
are  considered  in  the  discussion  of  physiological  oxidations  (see  p.  973). 

7.  The  deaminizing  enzymes,  which  by  hydrolytic  cleavage  split  off  an  NH2 

group  as  ammonia.  Thus  alanin  (aminopropionic  acid)  by  hydrolysis 
loses  its  NH2  group  as  ammonia  and  passes  into  lactic  acid. 

CH3CHNH2COOH  +  H2O  =  NH3  +  CH3CHOHCOOH. 

The  enzymes  contained  in  the  first,  second,  third,  and  fourth  (a) 
of  these  groups  are  the  ones  that  play  the  chief  roles  in  the  digestive 
processes,  and  it  will  be  noticed  that  they  all  act  by  hydrolysis,— 
that  is,  they  cause  the  molecules  of  the  substance  to  undergo  de- 
composition or  cleavage  by  a  reaction  with  water.  Thus,  in  the 
conversion  of  maltose  to  dextrose  by  the  action  of  maltase  the  re- 
action may  be  expressed  so : 

CufiaOu  +  H20  =  C6H]206  +  C6H12Oa. 

Maltose.  Dextrose.        Dextrose. 

And  the  hydrolysis  of  the  neutral  fats  by  lipase  may  be  expressed 
so: 

VfU&fLpOJt  +  3H20  =  OH^OH),  +  3(CMH,,p,). 

Tristearin.  Glycerin.  Stearic  acid. 

Protective  Enzymes. — Experimental  work  in  recent  years  has 
brought  out  the  interesting  and  important  fact  that  when  foreign 
proteins,  carbohydrates,  or  fats  are  introduced  into  the  blood  of  a 
living  animal  corresponding  enzymes  are  formed  which  are  adapted 
to  break  down  the  foreign  material  by  a  process  of  digestion.* 

*  Consult  Abderhalden,  "Schutzfermente  des  tierischen  organismus," 
1912;  also  Vaughan,  "Protein  Split  Products  in  Relation  to  Immunity  and 
Disease,"  1913,  and  "Journal  of  the  Amer.  Med.  Assoc.,"  August  1,  1914. 

48 


754  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

The  blood-serum  may  not  contain  any  proteolytic  enzyme  capable 
of  hydrolyzing  egg-albumin,  but  if  this  protein  is  injected  into  the 
animal  the  serum  will  then  be  found  to  contain  an  enzyme  that 
digests  egg-albumin.  Similarly,  if  cane  sugar  is  injected  the  blood- 
serum  will  show  the  presence  of  an  inverting  enzyme  that  splits 
the  cane-sugar  to  its  constituent  monosaccharids.  It  has  been 
claimed,  moreover,  that  if  any  of  the  cellular  material  of  the 
animal's  own  body,  not  normally  present  in  the  blood,  finds  its  way 
into  this  liquid,  enzymes  are  produced  capable  of  digesting  this 
blood-foreign  material.  It  has  been  stated  that  the  protective 
enzymes  thus  developed  show  a  considerable  degree  of  specificity 
to  the  particular  foreign  material  responsible  for  their  formation, 
and  efforts  have  been  made,  therefore,  to  utilize  the  fact  in  the 
diagnosis  of  abnormal  conditions,  the  method  being  designated  as 
the  Abderhalden  test,  after  the  name  of  the  physiologist  who  first 
proposed  its  use,  or  more  generally  as  the  method  of  serodiagnosis. 
Thus,  in  pregnancy,  cells  from  the  chorionic  villi  of  the  placenta 
get  into  the  blood  of  the  mother,  and  examination  of  her  blood- 
serum  shows  the  presence  of  an  enzyme  that  digests  placental  pro- 
teins. The  biological  reaction,  whereby  these  protective  enzymes 
are  produced,  is  similar  to  that  already  described  in  the  case  of  the 
formation  of  precipitins  (p.  425)  and  antibodies  in  general.  The 
validity  of  this  theory  of  specific  protective  enzymes  and  its  prac- 
tical application  in  serodiagnosis  is  at  present  under  investigation. 
Some  observers  have  failed  to  confirm  Abderhalden's  results.* 

General  Properties  of  Enzymes. — The  specific  reactions  of  the 
various  enzymes  of  the  body  are  referred  to  under  separate  heads. 
The  following  general  characteristics  may  be  noted  briefly: 

Solubility. — Most  of  the  enzymes  are  soluble  in  water  or  salt 
solutions,  or  in  glycerin.  By  these  means  they  may  be  extracted 
conveniently  from  the  various  tissues.  In  some  cases,  however,  such 
simple  methods  do  not  suffice,  particularly  for  the  endo-enzymes; 
the  enzyme  is  either  insoluble  or  is  destroyed  in  the  process  of  ex- 
traction, and  to  prove  its  presence  pieces  of  the  tissue  or  the  juice 
pressed  from  the  tissue  must  be  employed. 

Temperature. — The  body  enzymes  are  characterized  by  the  fact 
that  they  are  destroyed  by  high  temperatures  (60°  C.  to  80°  C.)  and 
that  their  effect  is  retarded  in  part  or  entirely  by  low  temperatures. 
Most  of  them  show  an  optimum  activity  at  temperatures  approxi- 
mating that  of  the  body. 

Precipitation,  Adsorption.— The  enzymes  are  precipitated  from 
their  solutions  in  part  at  least  by  excess  of  alcohol.  This  precipi- 
tation is  frequently  used  in  obtaining  purified  specimens  of  en- 
zymes. The  enzymes,  moreover,  show  an  interesting  tendency  to 

*  Oppler,  "Biochemische  Zeitschrift,"  75,  211, 1916,  and  Van  Slyke,  et.  al, 
"American  Journal  of  Obstetrics,"  73,  290,  1916. 


COMPOSITION    OF    FOOD   AND    ACTION    OF    ENZYMES.  755 

be  carried  down  mechanically  by  flocculent  precipitates  produced  in 
their  solutions.  If  protein  present  in  the  solution  is  precipitated, 
for  instance,  the  enzymes  may  be  carried  down  with  it  in  part. 
The  mode  of  union  of  the  enzyme  with  the  precipitate  in  these 
cases  comes  under  the  general  head  of  mechanical  adsorption.  It 
consists  in  a  concentration  of  the  enzyme  at  the  limiting  surface 
between  the  particles  of  the  precipitate  and  the  solution. 

Incompleteness  of  their  Action. — In  any  given  mixture  of  a  sub- 
stance and  its  enzyme  the  action  of  the  latter  is  usually  not  com- 
plete,— that  is,  all  of  the  substance  does  not  disappear.  One  ex- 
planation for  this  fact  has  been  found  in  the  reversibility  of  the 
action  of  the  enzyme.  If  the  reaction  proceeds  in  both  directions, 
then  evidently  under  fixed  conditions  a  final  equilibrium  will  be 
reached  in  which  no  further  apparent  change  takes  place,  although 
in  reality  the  condition  is  not  one  of  rest,  but  of  balance  between 
opposing  processes  proceeding  at  a  definite  rate.  In  addition  to 
this  factor  it  may  be  shown  in  some  cases  that  the  products  of  the 
reaction  serve  to  retard  further  action,  possibly  by  forming  a 
compound  of  some  kind  with  the  enzyme.  Within  the  body  itself, 
on  the  contrary,  the  action  of  an  enzyme  may  be  complete,  since 
the  products  are  removed  by  absorption. 

Active  and  Inactive  Form. — In  many  cases  it  can  be  shown 
that  the  enzyme  exists  within  the  cell  producing  it  in  an  inactive 
form  or  even  when  secreted  it  may  still  be  inactive.  This 
antecedent  or  inactive  stage  is  usually  designated  as  zymogen 
or  preferment.  The  zymogen  may  be  stored  in  the  cell  in  the 
form  of  granules  which  are  converted  into  active  enzyme  at  the 
moment  of  secretion,  or  it  may  be  secreted  in  inactive  form  and 
require  the  co-operation  of  some  other  substance  before  it  is 
capable  of  effecting  its  normal  reaction.  In  such  cases  the 
second  substance  is  said  to  activate  the  enzyme.  In  connection 
with  the  process  of  activation  various  terms  have  been  employed 
to  designate  the  substance  responsible  for  the  activation.  Accord- 
ing to  a  recent  classification*  it  has  been  suggested  that  inorganic 
substances  causing  activation  shall  be  designated  simply  as  acti- 
vators, while  organic  substances  playing  a  similar  role  shall  be  named 
kinases.  An  example  of  the  latter  is  found  in  the  case  of  the  entero- 
kinase  which  activates  the  trypsin  of  the  pancreatic  secretion. 

Coenzymes  or  Coferments. — In  addition  to  the  process  of  ac- 
tivation it  would  seem  that  in  some  cases  the  action  of  an  enzyme 
is  facilitated  by,  or  perhaps  is  even  dependent  upon  the  presence 
of  some  other  substance.  Perhaps  the  best  example  of  this  com- 
bined activity  is  furnished  by  the  influence  of  bile  salts  upon 
lipase  (p.  804) .  These  cases  of  coactivity  are  to  be  distinguished 
from  activation  by  the  fact  that  the  combination  may  be  easily 
*  Samuely,  in  "Handbuch  der  Biochemie,"  i.,  1908. 


756 


PHYSIOLOGY    OF    DIGESTION   AND    SECRETION. 


made  or  unmade,  that  is  to  say,  it  constitutes  a  reversible  reac- 
tion. In  a  mixture  of  bile  salts  and  lipase,  for  example,  the  bile 
salts  may  be  removed  by  dialysis.  In  activation,  on  the  contrary, 
we  have  an  irreversible  reaction  —  the  active  trypsin  cannot  be 
changed  to  the  inactive  trypsinogen.* 


PARTIAL  LIST  OF  THE  ENZYMES  CONCERNED  IN  THE  PROC- 
ESSES OF  DIGESTION  AND   NUTRITION. 


ENZTME. 

Ptyalin  (sali- 
vary diastase. 

Amylase  (pan- 
creatic dias- 
tase) . 

Liver  glyco- 
genase. 

Muscle  glyco- 
genase. 

Invertase. 

Maltase. 


Lactase. 
Glycolytic? 

{Lipase     (steap- 
sin). 

f  Pepsin. 
Trypsin. 
Erepsin. 


Group  of  auto- 
lytic  enzymes. 

Nucleases. 


Guanase. 


Adenase. 


^  Deaminase? 


WHERE  CHIEFLY 
FOUND. 

Salivary  secretion. 

Pancreatic  secre- 
tion. 

Liver. 
Muscles. 
Small  intestine. 

Small  intestine,  sali- 
vary and  pancre- 
atic secretion. 

Small  intestine. 

Muscles? 

Pancreatic  secre- 
tion, fat,  tissues, 
blood,  etc. 

Gastric  juice. 

Pancreatic  juice. 
Small  intestine. 


ACTION. 

Converts  starch  to  sugar 
(maltose). 

Converts  starch  to  sugar 
(maltose). 

Converts  glycogen  to  dex- 
trose. 

Converts  glycogen  to  dex- 
trose. 

Converts  cane-sugar  to 
dextrose  and  levulose. 

Converts  maltose  to  dex- 
trose. 

Converts  lactose  to  dex- 
trose and  galactose. 

Splits  and  oxidizes  dex- 
trose. 

Splits  neutral  fats  to  fatty 
acids  and  glycerin. 

Converts  proteins  to  pep- 
tones and  proteoses. 

Splits  proteins  into  their 
constituent  amino-acids. 

Splits  peptones  and  pro- 
teoses into  their  con- 
stituent amino-acids. 

Splits  proteins  into  nitrog- 
enous bases  and  ammo- 
bodies. 

Split  nucleic  acid  with  for- 
mation of  purin  bases, 
etc. 

Converts  guanin  to  xan- 
thin  by  splitting  off  an 
NH2  group  as  ammonia 
(NH3). 

Converts  adenin  to  hypo- 
xanthin  by  splitting  off 
an  NH2  group  as  am- 
monia (NHs). 

Splits  off  the  NH2  group 
from  the  amino-acids 
with  the  formation  of 
non-nitrogenous  organic 
acids. 

*  Consult  Bayliss,  "The  Nature  of  Enzyme  Action"  (series  of  monographs 
on  Biochemistry),  London,  1908. 


Tissues  generally. 


Pancreas,      spleen, 
thymus,  etc. 

Thymus,    adrenals, 
pancreas. 


Spleen,      pancreas, 
liver. 


Tissues  generally. 


COMPOSITION    OF    FOOD    AND    ACTION    OF    ENZYMES.          757 

Oxidases.  Lungs,   liver,   mus-      Cause  oxidation  of  organ- 

cle,  etc.  ic  substances,  as  in  the 

conversion  of  hypoxan- 

thin  to  xanthin  and  of 

xanthin  to  uric  acid. 

Reductases.  Tissues  generally.  Cause  reduction  or  deoxi- 

dation  as,  for  example, 
the  reduction  of  oxy- 
hemoglobin  to  hemo- 
globin. 

Catalase.  Many  tissues.  Decomposes         hydrogen 

Seroxid. 
ts    arginin    with   pro- 
duction   of    urea    and 
ornithin    (diamino-vale- 
rianic  acid). 

Chemical  Composition  of  the  Enzymes. — It  was  formerly 
believed  that  the  enzymes  belong  to  the  group  of  proteins.  They 
are  formed  from  living  matter,  and  their  solutions  as  usually 
prepared  give  protein  reactions.  Increased  study,  however,  has 
made  this  belief  uncertain.  The  enzymes  cling  to  the  proteins 
when  precipitated,  and  it  seems  possible  that  the  protein  reac- 
tions of  their  solutions  may  be  due,  therefore,  to  an  incomplete 
purification.  In  fact,  it  is  stated  that  solutions  of  some  of  the 
enzymes  may  be  prepared  which  show  ferment  activity,  but 
give  no  protein  reactions.  In  this  group  may  be  included  the 
lipase,  diastase,  invertase,  pepsin,  oxidase,  and  catalase.  Appar- 
ently, however,  all  enzymes  contain  nitrogen  and  most  of  them 
also  sulphur.  They  probably  also  contain  some  ash,  especially 
calcium.  Much  of  the  older  work  upon  the  composition  of 
supposedly  purified  preparations  of  enzymes  is  not  accepted 
to-day,  on  the  ground  that  the  evidence  for  the  purity  of  the 
preparations  is  insufficient.  In  spite,  however,  of  the  very  great 
amount  of  attention  that  has  been  paid  to  these  substances  in 
recent  years,  there  is  at  present  no  agreement  as  to  their  chemical 
structure.  The  statement  made  above  that  they  are  organic 
substances,  derived  from  proteins  and  of  a  colloidal  nature,  is 
perhaps  as  much  as  can  be  said  positively  in  regard  to  their 
chemical  structure.  As  a  rule,  they  are  destroyed  by  moderately 
high  temperatures  (80°  C.  or  below),  they  are  not  easily  diffusible 
through  parchment  membranes,  and,  like  the  proteins,  are  "  salted 
out  "  by  certain  concentrations  of  neutral  salts. 


CHAPTER  XLI. 

THE  SALIVARY  GLANDS  AND  THEIR  DIGESTIVE 
ACTION. 

The  first  of  the  secretions  with  which  the  food  comes  into  contact 
is  the  saliva.  This  is  a  mixed  secretion  from  the  large  salivary  glands 
and  the  small  unnamed  mucous  and  serous  glands  that  open  into  the 
mouth  cavity. 

The  Salivary  Glands. — The  salivary  glands  in  man  are  three 
in  number  on  each  side — the  parotid,  the  submaxillary,  and 
the  sublingual.  The  parotid  gland  communicates  with  the  mouth 
by  a  large  duct  (Stenson's  duct)  which  opens  upon  the  inner 
surface  of  the  cheek  opposite  the  second  molar  tooth  of  the  upper 
jaw.  The  submaxillary  gland  lies  below  the  lower  jaw,  and  its 
duct  (Wharton's  duct)  opens  into  the  mouth  cavity  at  the  side  of 
the  frenum  of  the  tongue.  The  sublingual  gland  lies  in  the  floor  of  the 
mouth  to  the  side  of  the  frenum  and  opens  into  the  mouth  cavity  by 
a  number  (eight  to  twenty)  of  small  ducts,  known  as  the  ducts  of 
Rivinus.  One  larger  duct  that  runs  parallel  with  the  duct  of  Whar- 
ton  and  opens  separately  into  the  mouth  cavity  is  sometimes  present 
in  man.  It  is  known  as  the  duct  of  Bartholin  and  occurs  normally  in 
the  dog. 

The  course  of  the  nerve  fibers  supplying  the  large  salivary  glands 
is  interesting  in  view  of  the  physiological  results  of  their  stimulation. 
The  description  here  given  applies  especially  to  their  arrangement 
in  the  dog.  These  glands  receive  their  nerve  supply  from  two  general 
sources, — namely,  the  bulbar  autonomies  (or  cerebral  fibers)  and 
the  sympathetic  autonomies.  The  parotid  gland  receives  its  bul- 
bar autonomic  fibers  from  the  glossopharyngeal  or  ninth  cranial 
nerve;  they  pass  into  a  branch  of  this  nerve,  known  as  the  tympanic 
branch  or  nerve  of  Jacobson,  thence  to  the  small  superficial  pe- 
trosal  nerve,  through  which  they  reach  the  otic  ganglion.  From 
this  ganglion  they  pass  (postganglionic  fibers)  by  way  of  the  auricu- 
lotemporal  branch  of  the  inferior  maxillary  division  of  the  fifth 
cranial  nerve  to  the  parotid  gland  (Fig.  288).  The  sympathetic 
autonomies  pass  to  the  superior  cervical  ganglion  by  way  of  the 
cervical  sympathetic  (Fig.  112),  and  thence  as  postganglionic  fibers 
in  branches  which  accompany  the  arteries  distributed  to  the  gland. 
The  bulbar  autonomic  supply  for  the  submaxillary  and  sublingual 

1758 


THE    SALIVARY    GLANDS. 


759 


glands  arises  from  the  brain  in  the  facial  nerve  and  passes  out  hi  the 
chorda  tympani  branch  (Fig.  289) .  This  latter  nerve,  after  emerging 
from  the  tympanic  cavity  through  the  Glaserian  fissure,  joins  the 


Ganglion. 
Fig.  288.— Schematic  representation  of  the  course  of  the  cerebral  fibers  to  the  parotid  gland 

lingual  nerve.  After  running  with  this  nerve  for  a  short  distance, 
the  secretory  (and  vasodilator)  nerve  fibers  destined  for  the  sub- 
maxillary and  sublingual  glands  branch  off  and  pass  to  the  glands, 


Fig.  289. — Schematic  representation  of  the  course  of  the  chorda  tympani  nerve  to  the 

submaxillary  gland. 

following  the  course  of  the  ducts.  Where  the  chorda  tympani  fibers 
'eave  the  lingual  there  is  a  small  ganglion  which  has  received  the 
name  of  submaxillary  ganglion.  The  nerve  fibers  to  the  glands 


760 


PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 


pass  close  to  this  ganglion,  but  Langley  has  shown  that  only  those 
destined  for  the  sublingual  gland  really  connect  with  the  nerve 
cells  of  the  ganglion,  and  he  suggests,  therefore,  that  it  should 
be  called  the  sublingual  instead  of  the  submaxillary  ganglion.  The 
nerve  fibers  for  the  submaxillary  gland  make  connections  with  nerve 
cells  lying  mainly  within  the  hilus  of  the  gland  itself.  The  supply 
of  sympathetic  autonomies  has  the  same  general  course  as  those 
for  the  parotid, — namely,  through  the  cervical  sympathetic  to  the 
superior  cervical  ganglion  and  thence  to  the  glands. 

Histological  Structure. — The  salivary  glands  belong  to  the  type 
of  compound  tubular  glands.  That  is,  the  secreting  portions  are 
tubular  in  shape,  although  in  cross-sections  these  tubes  may  pre- 
sent various  outlines  according  as  the  plane  of  the  section  passes 
through  them.  The  parotid  is  described  usually  as  a  typical  serous 
or  albuminous  gland.  Its  secreting  epithelium  is  composed  of  cells 
which  in  the  fresh  condition  as  well  as  in  preserved  specimens  contain 
numerous  fine  granules  and  its  secretion  contains  some  albumin. 
The  submaxillary  gland  differs  in  histology  in  different  animals. 
In  some,  as  the  dog  or  cat,  the  secretory  tubes  are  composed  chiefly 
or  exclusively  of  epithelial  cells  of  the  mucous  type.  In  man  the 
gland  is  of  a  mixed  type,  the  secretory  tubes  containing  both  mucous 
and  albuminous  cells.  The  sublingual  gland  in  man  also  contains 
both  varieties  of  cells,  although  the  mucous  cells  predominate.  In 
accordance  with  these  histological  characteristics  it  is  found  that  the 
secretion  from  the  submaxillary  and  sublingual  glands  is  thick  and 
mucilaginous  as  compared  with  that  from  the  parotid. 

The  salivary  glands  possess  definite  secretory  nerves  which  when 
stimulated  cause  the  formation  of  a  secretion.  This  fact  indicates 
that  there  must  be  a  direct  contact  of  some  kind  between  the  gland 
cells  and  the  terminations  of  the  secretory  fibers.  The  ending  of  the 
nerve  fibers  in  the  submaxillary  and  sublingual  glands  has  been  de- 
scribed by  a  number  of  observers.  *  The  accounts  differ  somewhat  as 
to  details  of  the  finer  anatomy,  but  it  seems  to  be  clearly  established 
that  the  secretory  fibers  from  the  chorda  tympani  end  first  around  the 
intrinsic  nerve  ganglion  cells  of  the  glands  (preganglionic  fibers),  and 
from  these  latter  cells  axons  (postganglionic  fibers)  are  distributed 
to  the  secreting  cells,  passing  to  these  cells  along  the  ducts.  The 
nerve  fibers  terminate  in  a  plexus  upon  the  membrana  propria  of  the 
alveoli,  and  from  this  plexus  fine  fibrils  pass  inward  to  end  on  and 
between  the  secreting  cells.  It  would  seem  from  these  observations 
that  the  nerve  fibrils  do  not  penetrate  or  fuse  with  the  gland  cells, 
as  was  formerly  supposed,  but  form  a  terminal  network  in  contact 
with  the  cells,  following  thus  the  general  schema  for  the  connection 
between  nerve  fibers  and  peripheral  tissues. 

*  See  Huber,  "Journal  of  Experimental  Medicine,"  1,  281,  1896. 


THE    SALIVARY    GLANDS.  761 

Composition  of  the  Secretion. — The  saliva  as  it  is  found  in  the 
mouth  is  a  colorless  or  opalescent,  turbid,  and  viscid  liquid  of 
weakly  alkaline  reaction  to  litmus  paper,  and  a  specific  gravity  of 
about  1.003.  It  may  contain  numerous  flat  cells  derived  from  the 
epithelium  of  the  mouth,  and  the  peculiar  spherical  cells  known  as 
salivary  corpuscles,  which  seem  to  be  altered  leucocytes.  The 
important  constituents  of  the  secretion  are  mucin,  a  diastatic  en- 
zyme known  as  ptyalin,  maltase,  traces  of  protein  and  of  potassium 
sulphocyanid,  and  inorganic  salts,  such  as  potassium  and  sodium 
chlorid,  potassium  sulphate,  sodium  carbonate,  and  calcium  car- 
bonate and  phosphate.  The  carbonates  are  particularly  abundant 
in  the  saliva,  and  the  secretion  in  addition  contains  much  carbon 
dioxid  in  solution.  Thus,  Pfliiger  found  that  65  volumes  per  cent, 
of  CO2  might  be  obtained  from  the  saliva,  of  which  42.5  per  cent, 
was  in  the  form  of  carbonates.  The  amount  of  CO2  in  solution 
and  combined  is  an  indication  of  the  active  chemical  changes 
occurring  in  the  gland. 

Of  the  organic  constituents  of  the  saliva  the  protein  exists  in 
small  and  variable  quantities,  and  its  exact  nature  is  not  determined. 
The  mucin  gives  to  the  saliva  its  ropy,  mucilaginous  character. 
This  substance  belongs  to  the  group  of  combined  proteins,  glyco- 
proteins  (see  Appendix),  consisting  of  a  protein  combined  with  a 
carbohydrate  group.  The  most  interesting  constituent  of  the  mixed 
saliva  is  the  ptyalin  or  salivary  diastase.  This  body  belongs  to  the 
group  of  enzymes  or  unorganized  ferments,  whose  general  properties 
have  been  described.  In  some  animals  (dog)  ptyalin  seems  to  be 
normally  absent  from  the  fresh  saliva. 

The  secretions  of  the  parotid  and  the  submaxillary  glands  can  be 
obtained  separately  by  inserting  a  cannula  into  the  openings  of  the 
ducts  in  the  mouth,  or,  according  to  the  method  of  Pawlow,  by  trans- 
ferring the  end  of  the  duct  so  that  it  opens  upon  the 'skin  instead  of 
in  the  mouth,  making  thus  a  salivary  fistula.  The  secretion  of  the 
sublingual  can  only  be  obtained  in  sufficient  quantities  for  analysis 
from  the  lower  animals.  Examination  of  the  separate  secretions 
shows  that  the  main  difference  lies  in  the  fact  that  the  parotid  saliva 
contains  no  mucin,  while  that  of  the  submaxillary  and  especially  of 
the  sublingual  gland  is  rich  in  mucin.  The  parotid  saliva  of  man 
seems  to  be  particularly  rich  in  ptyalin  as  compared  with  that  of  the 
submaxillary. 

The  Secretory  Nerves. — The  existence  of  secretory  nerves  to  the 
salivary  glands  was  discovered  by  Ludwig  in  1851.  The  discovery  is 
particularly  interesting  in  that  it  marks  the  beginning  of  our  knowl- 
edge of  this  kind  of  nerve  fiber.  Ludwig  found  that  stimulation  of 
the  chorda  tympani  nerve  causes  a  flow  of  saliva  from  the  submaxil- 
lary gland.  He  established  also  several  important  facts  with  regard 


762  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

to  the  pressure  and  composition  of  the  secretion  which  will  be  referred 
to  presently.  It  was  afterward  shown  that  the  salivary  glands  receive 
a  double  nerve  supply, — in  part  by  way  of  the  cervical  sympathetic 
and  in  part  through  cerebral  nerves.  It  was  discovered  also  that 
not  only  are  secretory  fibers  carried  to  the  glands  by  these  paths, 
but  that  vasomotor  fibers  are  contained  in  the  same  nerves, 
and  the  arrangement  of  these  latter  fibers  is  such  that  the  cerebral 
nerves  contain  vasodilator  fibers  that  cause  a  dilatation  of  the  small 
arteries  in  the  glands  and  an  accelerated  blood-flow,  while  the  sym- 
pathetic carries  vasoconstrictor  fibers  whose  stimulation  causes  a 
constriction  of  the  small  arteries  and  a  diminished  blood-flow.  The 
effect  of  stimulating  these  two  sets  of  fibers  is  found  to  vary  somewhat 
in  different  animals.  For  purposes  of  description  we  may  confine 
ourselves  to  the  effects  observed  on  dogs,  since  much  of  our  funda- 
mental knowledge  upon  the  subject  is  derived  from  Heidenhain's* 
experiments  upon  this  animal.  If  the  chorda  tympani  nerve  is 
stimulated  by  weak  induction  shocks,  the  gland  begins  to  secrete 
promptly,  and  the  secretion,  by  proper  regulation  of  the  stimulation, 
may  be  kept  up  for  hours.  The  secretion  thus  obtained  is  thin  and 
watery,  flows  freely,  is  abundant  in  amount,  and  contains  not  more 
than  1  or  2  per  cent,  of  total  solids.  At  the  same  time  there  is  an 
increased  flow  of  blood  through  the  gland.  The  whole  gland  takes 
on  a  redder  hue,  the  veins  are  distended,  and  if  cut  the  blood  that 
flows  from  them  is  of  a  redder  color  than  in  the  resting  gland,  and 
may  show  a  distinct  pulse — all  of  which  points  to  a  dilatation  of  the 
small  arteries.  If  now  the  sympathetic  fibers  are  stimulated,  quite 
different  results  are  obtained.  The  secretion  is  relatively  small  in 
amount,  flows  slowly,  is  thick  and  turbid,  and  may  contain  as  much 
as  6  per  cent,  of  total  solids.  At  the  same  time  the  gland  becomes 
pale,  and  if  the  veins  be  cut  the  flow  from  them  is  slower  than  in 
the  resting  gland,  thus  indicating  that  a  vasoconstriction  has 
occurred. 

The  increased  vascular  supply  to  the  gland  accompanying  the 
abundant  flow  of  "chorda  saliva"  and  the  diminished  flow  of  blood 
during  the  scanty  secretion  of  "sympathetic  saliva"  suggest  naturally 
the  idea  that  the  whole  process  of  secretion  may  be,  at  bottom,  a 
vasomotor  phenomenon,  the  amount  of  secretion  depending  only  on 
the  quantity  and  pressure  of  the  blood  flowing  through  the  gland. 
It  has  been  shown  conclusively  that  this  idea  is  erroneous  and  that 
definite  secretory  fibers  exist.  The  following  facts  may  be  quoted 
in  support  of  this  statement:  (1)  Ludwig  showed  that  if  a  mercury 
manometer  is  connected  with  the  duct  of  the  submaxillary  gland  and 
the  chorda  is  then  stimulated  for  a  certain  time,  the  pressure  in  the 

*  "Pfliiger's  Archiv  fiir  die  gesammte  Physiologie,"  17,  1,  1878;  also 
in  Hermann's  "Handbuch  der  Physiologie,"  1883,  vol.  v,  part  i. 


THE    SALIVARY    GLANDS.  763 

duct  may  become  greater  than  the  blood-pressure  in  the  gland. 
This  fact  shows  that  the  secretion  is  not  derived  entirely  by  processes 
of  filtration  from  the  blood.  (2)  If  the  blood-flow  be  shut  off 
completely  from  the  gland,  stimulation  of  the  chorda  still  gives  a 
secretion  for  a  short  time.  (3)  If  atropin  is  injected  into  the  gland, 
stimulation  of  the  chorda  causes  vascular  dilatation,  but  no 
secretion.  This  may  be  explained  by  supposing  that  the  atropin 
paralyzes  the  secretory,  but  not  the  dilator  fibers.  (4)  Hydro- 
chlorate  of  quinin  injected  into  the  gland  causes  vascular  dilatation, 
but  no  secretion.  In  this  case  the  secretory  fibers  are  still  irritable, 
since  stimulation  of  the  chorda  gives  the  usual  secretion. 

A  still  more  marked  difference  between  the  effect  of  stimulation 
of  the  cerebral  and  the  sympathetic  fibers  may  be  observed  in  the 
case  of  the  parotid  gland  in  the  dog.  Stimulation  of  the  cerebral 
fibers,  in  any  part  of  their  course,  gives  an  abundant,  thin,  and 
watery  saliva,  poor  in  solid  constituents.  Stimulation  of  the  sym- 
pathetic fibers  alone  (provided  the  cerebral  fibers  have  not  been 
stimulated  shortly  before  and  the  tympanic  nerve  has  been  cut  to 
prevent  a  reflex  effect)  gives  usually  no  perceptible  secretion  at  all. 
But  in  this  last  stimulation  a  marked  effect  is  produced  upon  the 
gland,  in  spite  of  the  absence  of  a  visible  secretion.  This  is  shown  by 
the  fact  that  subsequent  or  simultaneous  stimulation  of  the  cerebral 
fibers  causes  a  secretion  very  unlike  that  given  by  the  cerebral  fibers 
alone,  in  that  it  is  very  rich  indeed  in  organic  constituents.  The 
amount  of  organic  matter  in  the  secretion  may  be  tenfold  that  of  the 
saliva  obtained  by  stimulation  of  the  cerebral  fibers  alone. 

Relation  of  the  Composition  of  the  Secretion  to  the  Strength  of  Stimu- 
lation.— If  the  stimulus  to  the  chorda  is  gradually  increased  in 
strength,  care  being  taken  not  to  fatigue  the  gland,  the  chemical 
composition  of  the  secretion  is  found  to  change  with  regard  to  the 
relative  amounts  of  the  water,  the  salts,  and  the  organic  material. 
The  water  and  the  salts  increase  in  amount  with  the  increased 
strength  of  stimulus  up  to  a  certain  maximal  limit,  which  for  the 
salts  is  about  0.77  per  cent.  It  is  important  to  observe  that  this 
effect  may  be  obtained  from  a  perfectly  fresh  gland  as  well  as  from  a 
gland  which  had  previously  been  secreting  actively.  With  regard 
to  the  organic  constituents  the  precise  result  obtained  depends  on 
the  condition  of  the  gland.  If  previous  to  the  stimulation  the  gland 
was  in  a  resting  condition  and  unfatigued,  then  increased  strength 
of  stimulation  is  followed  at  first  by  a  rise  in  the  percentage  of  organic 
constituents,  and  this  rise  in  the  beginning  is  more  marked  than  in 
the  case  of  the  salts.  But  with  continued  stimulation  the  increase 
in  organic  material  soon  ceases,  and  finally  the  amount  begins  actually 
to  diminish,  and  may  fall  to  a  low  point  in  spite  of  the  stronger 
stimulation.  On  the  other  hand,  if  the  gland  at  the  beginning  of  the 


764  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

experiment  had  been  previously  worked  to  a  considerable  extent, 
then  an  increase  in  the  stimulating  current,  while  it  augments  the 
amount  of  water  and  salts,  either  may  have  no  effect  at  all  upon  the 
organic  constituents  or  may  cause  only  a  temporary  increase,  quickly 
followed  by  a  fall.  Similar  results  may  be  obtained  from  stimulation 
of  the  cerebral  nerves  of  the  parotid  gland.  The  above  facts  led 
Heidenhain  to  believe  that  the  conditions  determining  the  secretion 
of  the  organic  material  are  different  from  those  controlling  the  water 
and  salts,  and  he  gave  a  rational  explanation  of  the  differences 
observed,  in  his  theory  of  trophic  and  secretory  fibers. 

Theory  of  Trophic  and  Secretory  Nerve  Fibers. — This  theory 
supposes  that  two  physiological  varieties  of  nerve  fibers  are  distrib- 
uted to  the  salivary  glands.  One  of  these  varieties  controls  the 
secretion  of  the  water  and  inorganic  salts  and  its  fibers  may  be  called 
secretory  fibers  proper,  while  the  other,  to  which  the  name  trophic 
is  given,  causes  the  formation  of  the  organic  constituents  of  the  secre- 
tion, probably  by  a  direct  influence  on  the  metabolism  of  the  cells. 
Were  the  trophic  fibers  to  act  alone,  the  organic  products  would  be 
formed  within  the  cell,  but  there  would  be  no  visible  secretion,  and 
this  is  the  hypothesis  which  Heidenhain  uses  to  explain  the  results  of 
the  experiment  described  above  upon  stimulation  of  the  sympathetic 
fibers  to  the  parotid  of  the  dog.  In  this  animal,  apparently,  the 
sympathetic  branches  to  the  parotid  contain  exclusively  or  almost 
exclusively  trophic  fibers,  while  in  the  cerebral  branches  both  trophic 
and  secretory  fibers  proper  are  present.  The  results  of  stimulation 
of  the  cerebral  and  sympathetic  branches  to  the  submaxillary  gland 
of  the  same  animal  may  be  explained  in  terms  of  this  theory  by 
supposing  that  in  the  latter  nerve  trophic  fibers  preponderate,  and 
in  the  former  the  secretory  fibers  proper. 

It  is  obvious  that  this  anatomical  separation  of  the  two  sets  of 
fibers  along  the  cerebral  and  sympathetic  paths  may  be  open  to 
individual  variations,  and  that  dogs  may  be  found  in  which  the  sym- 
pathetic branches  to  the  parotid  glands  contain  secretory  fibers 
proper,  and  therefore  give  some  flow  of  secretion  on  stimulation. 
These  variations  might  also  be  expected  to  be  more  marked  when 
animals  of  different  groups  are  compared.  Thus,  Langley*  finds 
that  in  cats  the  sympathetic  saliva  from  the  submaxillary  gland  is 
less  viscid  than  the  chorda  saliva, — just  the  reverse  of  what  occurs 
in  the  dog.  To  apply  Heidenhain's  theory  to  this  case  it  is  necessaiy 
to  assume  that  in  the  cat  the  trophic  fibers  run  chiefly  in  the  chorda. 

The  way  in  which  the  trophic  fibers  act  has  been  briefly  indicated. 
They  may  be  supposed  to  set  up  metabolic  changes  in  the  proto- 
plasm of  the  cells,  leading  to  the  formation  of  certain  definite  prod- 

*  "Journal  of  Physiology,"  1,  96,  1878. 


THE    SALIVARY    GLANDS.  765 

ucts,  such  as  mucin  or  ptyalin.  That  such  changes  do  occur  is 
abundantly  shown  by  microscopical  examination  of  the  resting  and 
the  active  gland,  the  details  of  which  will  be  given  presently. 
That  these  changes  involve  processes  of  oxidation  is  shown  by  the 
fact  that  during  activity  the  gland  takes  up  more  oxygen  and  gives 
off  more  carbon  dioxid.  There  is  evidence  to  show  that  these 
gland  cells  during  activity  form  fresh  material  from  the  nourish- 
ment supplied  by  the  blood;  that  is,  that  anabolic  or  synthetic 
processes  occur  along  with  the  catabolic  changes.  The  latter  are 
the  more  obvious,  and  are  the  changes  which  are  usually  associated 
with  the  action  of  the  trophic  nerve  fibers. 

The  method  of  action  of  the  secretory  fibers  proper  is  difficult  to 
understand.  At  present  the  theories  suggested  are  entirely  specula- 
tive. Experiments  have  shown  that  the  amount  of  water  given 
off  from  the  blood  during  secretion  is  somewhat  greater  than  the 
amount  contained  in  the  saliva,*  and  there  is  reason  to  believe  that 
the  difference  between  the  two  is  accounted  for  by  an  increase  in 
the  flow  of  lymph  from  the  gland  during  activity.  A  satisfactory 
explanation  of  the  causes  leading  to  and  controlling  the  flow  of 
water  cannot  yet  be  given.  In  a  general  way  it  has  been  assumed 
that  the  effect  of  the  nerve  impulses  is  to  cause  the  production 
of  substances  within  the  cells  whereby  their  osmotic  pressure 
is  increased,  and  a  stream  of  water  is  set  up  from  the  blood  in 
the  capillaries  toward  the  gland  cells,  but  it  cannot  be  said  that 
this  assumption  has  been  supported  by  the  experiments  so  far 
made.f  We  must  limit  ourselves  to  the  more  general  statement 
that  the  activity  of  the  cells  themselves  initiates  and  controls 
the  flow  of  water. 

Histological  Changes  During  Activity0 — The  cells  of  both  the 
albuminous  and  mucous  glands  undergo  distinct  histological 
changes  in  consequence  of  prolonged  activity,  and  these  changes 
may  be  recognized  both  in  preparations  from  the  fresh  gland 
and  in  preserved  specimens.  In  the  parotid  gland  Heidenhain 
studied  the  changes  in  stained  sections  after  hardening  in 
alcohol.  In  the  resting  gland  the  cells  are  compactly  filled 
with  granules  that  stain  readily  and  are  imbedded  in  a  clear 
ground  substance  that  does  not  stain.  The  nucleus  is  small  and 
more  or  less  irregular  in  outline.  After  stimulation  of  the 
tympanic  nerve  the  cells  show  but  little  alteration,  but  stimula- 
tion of  the  sympathetic  produces  a  marked  change.  The  cells 
become  smaller,  the  nuclei  more  rounded,  and  the  granules  more 
closely  packed.  This  last  appearance  seems,  however,  to  be 

*  Barcroft,  "Journal  of  Physiology,"  1900,  25,  479. 

t  Carlson,  Greer,  and  Becht,  "American  Journal  of  Physiology,"  19,  360. 
1907. 


PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 


due  to  the  hardening  reagents  used.  A  truer  picture  of  what  occurs 
may  be  obtained  from  a  study  of  sections  of  the  fresh  gland.  Lang- 
ley,*  who  first  used  this  method,  describes  his  results  as  follows: 
When  the  animal  is  in  a  fasting  condition  the  cells  have  a  granular 
appearance  throughout  their  substance,  the  outlines  of  the  different 
cells  being  faintly  marked  by  light  lines  (Fig.  290,  A).  When  the 
gland  is  made  to  secrete  by  giving  the  animal  food,  by  injecting 
pilocarpin,  or  by  stimulating  the  sympathetic  nerves,  the  granules 
begin  to  disappear  from  the  outer  borders  of  the  cells  (Fig.  290,  B), 


Fig.  290. — Parotid  gland  of  the  rabbit  in  a  fresh  state,  showing  portions  of  the  secret- 
ing tubules:  A,  In  a  resting  condition;  B,  after  secretion  caused  by  pilocarpin;  C,  after 
stronger  secretion,  pilocarpin  and  stimulation  of  sympathetic;  D,  after  long-continued 
stimulation  of  sympathetic. — (After  Langley.) 

so  that  each  cell  now  shows  an  outer,  clear  border  and  an  inner 
granular  one.  If  the  stimulation  is  continued  the  granules  become 
fewer  in  number  and  are  collected  near  the  lumen  and  the  margins 
of  the  cells,  the  clear  zone  increases  in  extent,  and  the  cells  become 
smaller  (Fig.  290,  C,  D).  Evidently  the  granular  material  is  used 
in  some  way  to  make  the  organic  material  of  the  secretion.  Since  the 
ptyalin  is  a  conspicuous  organic  constituent  of  the  secretion,  it  is 
assumed  that  the  granules  in  the  resting  gland  contain  the  ptyalin, 
or  rather  the  preliminary  material  from  which  the  ptyalin  is  con- 
structed during  the  act  of  secretion.  On  this  latter  assumption  the 
granules  are  frequently  spoken  of  as  zymogen  granules.  During  the 
act  of  secretion  two  distinct  processes  seem  to  be  going  on  in  the  cell, 
leaving  out  of  consideration,  for  the  moment,  the  secretion  of  the 

*  "Journal  of  Physiology,"  2,  260,  1879. 


THE    SALIVARY    GLANDS. 


767 


Fig.  291. — Mucous  gland:  submaxillary  of  dog;  rest- 
ing stage. 


water  and  the  salts.  In  the  first  place,  the  zymogen  granules  undergo 
a  change  such  that  they  are  forced  or  dissolved  out  of  the  cell,  and, 
second,  a  constructive  metabolism  or  anabolism  is  set  up,  leading  to 
the  formation  of  new  pro- 
toplasmic material  from 
the  substances  contained 
in  the  blood  and  lymph. 
The  new  material  thus 
formed  is  the  clear,  non- 
granular  substance, 
which  appears  first 
toward  the  basal  sides  of 
the  cells.  We  may  sup- 
pose that  the  clear  sub- 
stance during  the  resting 
periods  undergoes  meta- 
bolic changes,  whether  of 
a  catabolic  or  anabolic 
character  can  not  be 

safely  asserted,  leading  to  the  formation  of  new  granules,  and  the 
cells  are  again  ready  to  form  a  secretion  of  normal  composition. 
It  should  be  borne  in  mind  that  in  these  experiments  the  glands 
were  stimulated  beyond  normal  limits.  Under  ordinary  conditions 
the  cells  are  probably  never  depleted  of  their  granular  material  to 
the  extent  represented  in  the  figures. 

In  the  cells  of  the  mucous  glands  changes  equally  marked  may 
be  observed  after  prolonged  activity.     In  stained  sections  of  the 

resting  gland  the  cells  are 
large  and  clear  (Fig.  291), 
with  flattened  nuclei 
placed  well  toward  the 
base  of  the  cell.  When 
the  gland  is  made  to  se- 
crete the  nuclei  become 
more  spherical  and  lie 
more  toward  the  middle 
of  the  cell,  and  the  cells 
themselves  become  dis- 
tinctly smaller.  After 
prolonged  secretion  the 
changes  become  more 
marked  (Fig.  292)  and,  according  to  Heidenhain,  some  of  the 
mucous  cells  may  break  down  completely.  According  to  most 
of  the  later  observers,  however,  the  mucous  cells  do  not  actually 
disintegrate,  but  form  again  new  material  during  the  period  of 


Fig.  292.— Mucous  gland:  submaxillary  of 
dog  after  eight  hours'  stimulation  of  the  chorda 
tympani. 


768  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

rest,  as  in  the  case  of  the  goblet  cells  of  the  intestine.  In  the 
mucous  as  in  the  albuminous  cells  observations  upon  pieces  of 
the  fresh  gland  seem  to  give  more  reliable  results  than  those  upon 
preserved  specimens.  Langley*  has  shown  that  in  the  fresh 
mucous  cells  of  the  submaxillary  gland  numerous  large  granules 
may  be  discovered,  about  125  to  250  to  a  cell.  These  granules 
are  comparable  to  those  found  in  the  goblet  cells,  and  may  be 
interpreted  as  consisting  of  mucin  or  some  preparatory  material 
from  which  mucin  is  formed.  The  granules  are  sensitive  to  re- 
agents; addition  of  water  causes  them  to  swell  up  and  disappear. 
It  may  be  assumed  that  this  happens  during  secretion,  the  gran- 
ules becoming  converted  to  a  mucin  mass  which  is  extruded  from 
the  cell. 

Action  of  Atropin,  Pilocarpin,  and  Nicotin  upon  the  Secre- 
tory Nerves. — The  action  of  drugs  upon  the  salivary  glands  and 
their  secretions  belongs  properly  to  pharmacology,  but  the  effects 
of  the  three  drugs  mentioned  are  so  decided  that  they  have  a 
peculiar  physiological  interest.  Atropin  in  small  doses  injected 
either  into  the  blood  or  into  the  gland  duct  prevents  the  action  of 
the  cerebral  autonomic  fibers  (tympanic  nerve  or  chorda  tympani) 
upon  the  glands.  This  effect  may  be  explained  by  assuming  that 
the  atropin  paralyzes  the  endings  of  the  cerebral  fibers  in  the  glands. 
That  it  does  not  act  directly  upon  the  gland  cells  themselves  seems 
to  be  assured  by  the  interesting  fact  that,  with  doses  sufficient  to 
throw  out  entirely  the  secreting  action  of  the  cerebral  fibers,  the 
sympathetic  fibers  are  still  effective  when  stimulated.  Pilocarpin 
has  directly  the  opposite  effect  to  atropin.  In  minimal  doses  it 
sets  up  a  continuous  secretion  of  saliva,  which  may  be  explained  upon 
the  supposition  that  it  stimulates  the  endings  of  the  secretory  fibers 
in  the  gland.  Within  certain  limits  these  drugs  antagonize  each 
other, — that  is,  the  effect  of  pilocarpin  may  be  removed  by  the  sub- 
sequent application  of  atropin,  and  vice  versa.  Kicotin,  according 
to  the  experiments  of  Langley,  f  prevents  the  action  of  the  secretory 
nerves,  not  by  affecting  the  gland  cells  or  the  endings  of  the  nerve 
fibers  around  them,  but  by  paralyzing  the  connections  between  the 
nerve  fibers  and  the  ganglion  cells  through  which  the  fibers  pass  on 
their  way  to  the  gland, — that  is,  the  connection  between  the  pre- 
ganglionic  and  postganglionic  fibers.  If,  for  example,  the  superior 
cervical  ganglion  is  painted  with  a  solution  of  nicotin,  stimulation 
of  the  cervical  sympathetic  below  the  gland  gives  no  secretion;  stim- 
ulation, however,  of  the  fibers  in  the  ganglion  or  between  the  ganglion 
and  gland  gives  the  usual  effect.  By  the  use  of  this  drug  Langley  is 
led  to  believe  that  the  cells  of  the  so-called  submaxillary  ganglion 

*  "Journal  of  Physiology,"  10,  433,  1889. 

t  "Proceedings  of  the  Royal  Society,"  London,  46,  423,  1889. 


THE    SALIVARY    GLANDS.  769 

are  really  intercalated  in  the  course  of  the  fibers  to  the  sublingual 
gland,  while  the  nerve  cells  with  which  the  submaxillary  fibers  make 
connection  are  found  chiefly  in  the  hilus  of  the  gland  itself. 

Paralytic  Secretion. — A  remarkable  phenomenon  in  connection 
with  the  salivary  glands  is  the  so-called  paralytic  secretion.  It  has 
been  known  for  a  long  time  that  if  the  chorda  tympani  is  cut  the 
submaxillary  gland  after  a  certain  time,  one  to  three  days,  begins  to 
secrete  slowly,  and  the  secretion  continues  uninterruptedly  for  a  long 
period — as  long,  perhaps,  as  several  weeks — and  eventually  the  gland 
itself  undergoes  atrophy.  Langley  states  that  section  of  the  chorda 
on  one  side  is  followed  by  a  continuous  secretion  from  the  glands 
on  both  sides;  the  secretion  from  the  gland  of  the  opposite  side  he 
designates  as  the  antiparalytic  or  antilytic  secretion.  After  section 
of  the  chorda  the  nerve  fibers  peripheral  to  the  section  degenerate, 
the  process  being  completed  within  a  few  days.  These  fibers,  how- 
ever, do  not  run  directly  to  the  gland  cell;  they  terminate  in 
synapses  around  sympathetic  nerve  cells  placed  somewhere  along 
their  course, — in  the  sublingual  ganglion,  for  instance,  or  within  the 
gland  substance  itself.  It  is  the  axons  from  these  second  nerve  units 
that  end  around  the  secreting  cells.  Langley  has  accumulated  some 
facts  to  show  that  within  the  period  of  continuance  of  the  paralytic 
secretion  (five  to  six  weeks)  the  fibers  of  the  sympathetic  cells  are 
still  irritable  to  stimulation.  He  is  inclined  to  believe,  therefore,  that 
the  continuous  secretion  is  due  to  a  continuous  excitation,  from  some 
cause,  of  the  local  nervous  mechanism  in  the  gland.  A  natural 
extension  of  this  view  which  has  been  suggested  (Pawlow)  is 
that  normally  the  activity  of  the  sympathetic  cells  or  of  the 
secreting  cells  is  kept  in  check  by  inhibitory  fibers.  After  section 
of  the  chorda  the  action  of  these  fibers  falls  out  and  the  secre- 
tion continues  until  the  glandular  tissue  undergoes  atrophy. 

Normal  Mechanism  of  Salivary  Secretion. — Under  normal  con- 
ditions the  flow  of  saliva  from  the  salivary  glands  is  the  result  of 
a  reflex  stimulation  of  the  secretory  nerves.  The  sensory  fibers 
concerned  in  this  reflex  must  be  chiefly  fibers  of  the  glossopharyn- 
geal  and  lingual  nerves  supplying  the  mouth  and  tongue.  Sapid 
bodies  and  various  other  chemical  or  mechanical  stimuli  applied 
to  the  tongue  or  mucous  membrane  of  the  mouth  produce  a 
flow  of  saliva.  The  normal  flow  during  mastication  must 
be  effected  by  a  reflex  of  this  kind,  the  sensory  im- 
pulse being  carried  to  a  center  and  thence  transmitted  through 
the  efferent  nerves  to  the  glands.  It  is  found  that  section 
of  the  chorda  prevents  the  reflex,  in  spite  of  the  fact  that  the 
sympathetic  fibers  are  still  intact.  No  satisfactory  explanation 
of  the  normal  functions  of  the  secretory  fibers  in  the  sympathetic 
has  yet  been  given.  Various  authors  have  suggested  that  possibly 
49 


770  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

the  three  large  salivary  glands  respond  normally  to  different  stimuli. 
This  view  has  been  supported  by  Pawlow,  who  reports  that  in 
the  dog  at  least  the  parotid  and  the  submaxillary  may  react  quite 
differently.  When  fistulas  were  made  of  the  ducts  of  these  glands  it 
was  found  that  the  submaxillary  responded  readily  to  a  great  num- 
ber of  stimuli,  such  as  the  sight  of  food,  chewing  of  meats,  acids,  etc. 
The  parotid,  on  the  contrary,  seemed  to  react  only  when  dry  food, 
dry  powdered  meat,  or  bread  was  placed  in  the  mouth.  Dryness  in 
this  case  appeared  to  be  the  efficient  stimulus. 

Pawlow  lays  great  stress  upon  the  adaptability  of  the  secretion  of  saliva 
to  the  character  of  the  material  chewed.  Dry,  solid  food  stimulates  a  large 
flow  of  saliva,  such  as  is  necessary  in  order  to  chew  it  properly  and  to  form  it 
into  a  bolus  for  swallowing.  Foods  containing  much  water,  on  the  contrary, 
excite  but  little  flow  of  saliva.  If  one  places  a  handful  of  clean  stones  in 
the  mouth  of  a  dog  he  will  move  them  around  with  his  tongue  for  a  while 
and  then  drop  them  from  his  mouth;  but  little  or  no  saliva  is  secreted. 
If  the  same  material  is  given  in  the  form  of  fine  sand  a  rich  flow  of  saliva 
is  produced,  and  the  necessity  for  the  reflex  is  evident  in  this  case,  since 
otherwise  the  material  could  not  be  conveniently  removed  from  the  mouth. 
Such  adaptations  must  be  regarded  from  the  physiological  point  of  view 
as  special  reflexes  depending  upon  some  difference  in  the  nervous  mechanism 
set  into  play.* 

Since  the  flow  of  saliva  is  normally  a  definite  reflex,  we  should 
expect  a  distinct  salivary  secretion  center.  This  center  has  been 
located  by  physiological  experiments  in  the  medulla  oblongata,  in 
the  formatio  reticularis  lateral  to  the  facial  nucleus.  The  experi- 
ments f  consisted  in  dividing  the  chorda  and  the  nervus  tympan- 
icus  and,  after  a  suitable  interval,  examining  sections  of  the  medulla 
for  the  appearance  of  degenerative  changes  (chromatolysis,  p.  128). 
Owing  to  the  wide  connections  of  nerve  cells  in  the  central  nervous 
system,  we  should  expect  this  center  to  be  affected  by  stimuli  from 
various  sources.  As  a  matter  of  fact,  it  is  known  that  the  center 
and  through  it  the  glands  may  be  called  into  activity  by  stimula- 
tion of  the  sensory  fibers  of  the  sciatic,  splanchnic,  and  particularly 
the  vagus  nerves.  So,  too,  various  psychical  acts,  such  as  the 
thought  of  savory  food  and  the  feeling  of  nausea  preceding  vomit- 
ing, may  be  accompanied  by  a  flow  of  saliva,  the  effect  in  this  case 
being  due  probably  to  stimulation  of  the  secretion  center  by  ner- 
vous impulses  descending  from  the  higher  nerve  centers.  Lastly, 
the  medullary  center  may  be  inhibited  as  well  as  stimulated.  The 
well-known  effect  of  fear,  embarrassment,  or  anxiety  in  producing 
a  parched  throat  may  be  explained  in  this  way  as  due  to  the  inhibit- 
ory action  of  nerve  impulses  arising  in  the  cerebral  centers. 

*  See  Pawlow,  "The  Work  of  the  Digestive  Glands,"  translation  by 
Thompson,  London,  1902;  also  "Ergebnisse  der  Physiologic,"  voh  iii.,  part  i, 
1904,  and  "Archives  Internationales  de  physiologic,"  1,  119,  1904.' 

t  Yagita  and  Hayama,  "Neurologisches  Centralblatt,"  738,  1909. 


THE    SALIVARY    GLANDS.  771 

Electrical  Changes  in  the  Gland  during  Activity. — It  has  been 
shown  that  the  salivary  as  well  as  other  glands  suffer  certain  changes 
in  electrical  potential  during  activity  which  are  comparable  in  a  gen- 
eral way  to  the  " action  currents"  observed  in  muscles  and  nerves.* 

The  Digestive  Action  of  Saliva — Ptyalin. — The  digestive  action 
proper  of  the  saliva  is  limited  to  the  starchy  food.  In  human 
beings  and  most  mammals  the  saliva  contains  an  active  enzyme 
belonging  to  the  group  of  diastases  and  designated  usually  as  ptyalin 
or  salivary  diastase.  It  may  be  prepared  in  purified  form  from  saliva 
by  precipitation  with  alcohol,  but  its  chemical  nature,  like  that  of  the 
other  enzymes,  is  still  an  unsolved  problem.  In  some  animals 
(horse)  it  is  stated  that  the  ptyalin  as  secreted  from  the  gland  is  in 
an  inactive  or  zymogen  form.  On  coming  into  contact  with  the 
mucous  membrane  of  the  mouth  it  is  converted  to  active  ptyalin 
by  an  organic  kinase,  orokinase,^  said  to  be  produced  in  the 
small  buccal  glands  found  in  the  mucous  membrane  of  the 
cheek  and  lips.  Saliva  or  preparations  of  ptyalin  act  readily 
upon  boiled  starch,  converting  it  into  sugar  and  dextrin.  This 
action  may  be  demonstrated  very  readily  by  holding  a  little 
starch  paste  or  starchy  food,  such  as  boiled  potatoes,  in  the 
mouth  for  a  few  moments.  If  the  solution  is  then  examined  the 
presence  of  sugar  is  readily  shown  by  its  reducing  action  on  solutions 
of  copper  sulphate  (Fehling's  solution).;  There  is  no  doubt  that  the 
action  of  ptyalin  upon  the  starch  is  hydrolytic.  Under  the  influence 
of  the  enzyme  the  starch  molecules  take  up  water  and  undergo 
cleavage  into  simpler  molecules.  The  steps  in  the  process  and  the 
final  products  have  been  investigated  by  a  very  large  number  of 
workers,  but  much  yet  remains  in  doubt.  The  following  points 
seem  to  be  determined:  The  end-result  of  the  reaction  is  the 
formation  of  maltose,  a  disaccharid,  having  the  general  formula 
C^H^OH,  and  some  form  of  dextrin,  a  non-crystallizable  poly- 
saccharid.  When  the  digestion  is  effected  in  a  vessel  some  dextrose 
(C6H1206)  may  be  found  among  the  products,  but  this  is  explained  on 
the  assumption  that  there  is  present  in  the  saliva  some  maltase,  an 
enzyme  capable  of  splitting  maltose  into  dextrose.  So  far  as  the 
ptyalin  itself  is  concerned,  its  specific  action  is  to  convert  starch  to 
maltose  and  dextrin.  It  seems  very  certain,  however,  that  a  number 
of  intermediate  products  are  formed  consisting  of  a  variety  of  dex- 
trins,  so  that  the  hydrolysis  probably  takes  place  in  successive 
stages.  There  is  little  agreement  as  to  the  exact  nature  of  the  in- 
termediate dextrins.  The  following  facts,  however,  may  be  easily 
demonstrated  in  a  salivary  digestion  carried  on  in  a  vessel  and  ex- 

*  See  Biedermann,  "Electro-physiology,"  translation  by  Welby,  London, 
1896. 

t  See  Palmer,  et.  al.,  "American  Journal  of  Physiology,"  43,  457,  1917. 


772  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

amined  from  time  to  time.  The  starch  at  first  gives  its  deep-blue 
reaction  with  iodin;  later,  instead  of  a  blue,  a  red  reaction  is  obtained 
with  iodin,  and  this  has  been  attributed  to  a  special  form  of  dextrin, 
erythrodextrin,  so  named  on  account  of  its  red  reaction.  Still  later 
this  reaction  fails  and  chemical  examination  shows  the  presence  of 
maltose  and  a  form  of  dextrin  which  gives  no  color  reaction  with 
iodin  and  is  therefore  named  achroodextrin.  While  the  number 
of  intermediate  products  may  be  large,  the  main  result  of  the  action 
of  the  ptyalin  is  expressed  by  the  following  simple  schema: 


The  products  formed  in  this  reaction  are  probably  not  absorbed  as 
such.  The  absorption  takes  place  mainly  no  doubt  after  the  food 
reaches  the  small  intestine,  and  we  have  evidence,  as  will  be  stated, 
that  before  absorption  the  maltose  is  acted  upon  by  the  inverting 
enzymes  (maltase)  and  converted  into  the  simple  sugar,  dex- 
trose. The  ptyalin  digestion  seems,  therefore,  to  be  prepara- 
tory, and  the  combined  action  of  ptyalin  and  maltase  is  necessary 
to  get  the  starch  into  a  condition  ready  for  nutrition.  Under 
the  influence  of  these  two  enzymes,  the  complex  starch  molecule, 
consisting  of  a  number  of  CeHioOs  groups,  is  broken  down  into  its 
constituent  elements  or  building  stones,  that  is  to  say,  to  the 
simple  sugars  of  the  formula  CeH^Oe.  The  simple  sugars  or  mono- 
saccharids  (CeH^Oe),  the  double  sugars  or  disaccharids  (C^H^On), 
and  the  dextrins,  starches,  and  cellulose  or  polysaccharids,  with 
the  general  formula  (CeHioC^n,  constitute  a  series  of  increasing 
complexity  as  regards  the  size  of  the  molecule.  By  hydrolysis, 
with  enzymes  or  with  acids,  the  polysaccharids  are  hydrated  and 
split  to  form  the  simpler  members  of  the  series,  while  on  the  other 
hand,  in  the  living  organism  the  simple  sugars  may  be  synthesized 
by  combining  two  or  more  of  the  groups  with  dehydration  to  form 
the  higher  polysaccharids,  the  animal  and  vegetable  starches. 
A  question  of  practical  importance  is  as  to  how  far  salivary  diges- 
tion affects  the  starchy  foods  under  usual  circumstances.  The 
chewing  process  in  the  mouth  thoroughly  mixes  the  food  and 
saliva,  or  should  do  so,  but  the  bolus  is  swallowed  much  too  quickly 
to  enable  the  enzyme  to  complete  its  action.  In  the  stomach 
the  gastric  juice  is  sufficiently  acid  to  destroy  the  ptyalin,  and  it 
was  therefore  supposed  formerly  that  salivary  digestion  is  promptly 
arrested  on  the  entrance  of  the  food  into  the  stomach,  and  is 
normally  of  but  little  value  as  a  digestive  process.  Our  recent 
increase  in  knowledge  regarding  the  conditions  in  the  stomach 
(p.  728)  shows,  on  the  contrary,  that  some  of  the  food  in  an  ordi- 
nary meal  may  remain  in  the  f  undic  end  of  the  stomach  for  an  hour 


THE    SALIVARY   GLANDS.  773 

or.  more  untouched  by  the  acid  secretion.  There  is  every  reason  to 
believe,  therefore,  that  salivary  digestion  may  be  carried  on  in  trie 
stomach  to  an  important  extent. 

Conditions  Influencing  the  Action  of  Ptyalin.— Temperature. 
— As  in  the  case  of  the  other  enzymes,  ptyalin  is  very  susceptible  to 
changes  of  temperature.  At  0°  C.  its  activity  is  said  to  be  suspended 
entirely.  The  intensity  of  its  action  increases  with  increase  of 
temperature  from  this  point,  and  reaches  its  maximum  at  about 
40°  G.  If  the  temperature  is  raised  much  beyond  this  point,  the 
action  decreases,  and  at  from  65°  to  70°  C.  the  enzyme  is  destroyed. 
In  these  latter  points  ptyalin  differs  from  diastase,  the  enzyme  of 
malt.  Diastase  shows  a  maximum  action  at  50°  C.  and  is  destroyed 
at80°C. 

Effect  of  Reaction. — The  normal  reaction  of  saliva  is  slightly 
alkaline  to  litmus.  Chittenden  has  shown,  however,  that  ptyalin 
acts  as  well,  or  even  better,  in  a  perfectly  neutral  medium.  A 
strong  alkaline  reaction  retards  or  prevents  its  action.  The  most 
marked  influence  is  exerted  by  acids.  Free  hydrochloric  acid 
to  the  extent  of  only  0.003  per  cent.  (Chittenden)  is  sufficient 
to  practically  stop  the  amylolytic  action  of  the  enzyme,  and  a 
slight  further  increase  in  acidity  not  only  stops  the  action,  but  also 
destroys  the  enzyme. 

Condition  of  the  Starch. — It  is  a  well-known  fact  that  the  conver- 
sion of  starch  to  sugar  by  enzymes  takes  place  much  more  rapidly 
with  cooked  starch — for  example,  starch  paste.  In  the  latter  ma- 
terial sugar  begins  to  appear  in  a  few  minutes,  provided  a  good 
enzyme  solution  is  used.  With  starch  in  a  raw  condition,  on  the 
contrary,  it  may  be  many  minutes,  or  even  several  hours,  before 
sugar  can  be  detected.  The  longer  time  required  for  raw  starch  is 
partly  explained  by  the  fact  that  the  starch  grains  are  surrounded 
by  a  layer  of  cellulose  or  cellulose-like  material  that  resists  the  action 
of  ptyalin.  When  boiled,  this  layer  breaks  and  the  starch  in  the 
interior  becomes  exposed.  In  addition,  the  starch  itself  is  changed 
during  the  boiling;  it  takes  up  water,  and  in  this  hydra  ted  condition 
is  acted  upon  more  rapidly  by  the  ptyalin.  The  practical  value  of 
cooking  vegetable  foods  is  evident  from  these  statements. 

Functions  of  the  Saliva. — In  addition  to  the  digestive  action  of 
the  saliva  on  starchy  foods  it  fulfills  other  important  functions.  By 
moistening  the  food  it  enables  us  to  reduce  the  material  to  a  consis- 
tency suitable  for  swallowing  and  for  manipulation  by  the  tongue  and 
other  muscles.  Moreover,  the  presence  of  mucin  serves  doubtless 
as  a  kind  of  lubricator  that  insures  a  smooth  passage  along  the 
esophageal  canal.  Finally  by  dissolving  dry  and  solid  food  it  pro- 
vides a  necessary  step  in  the  process  of  stimulating  the  taste  nerves, 
and,  as  is  described  below,  the  activity  of  the  taste  sensations  may 
play  an  important  part  in  the  secretion  of  the  gastric  juice. 


CHAPTER  XLII. 
DIGESTION  AND  ABSORPTION  IN  THE  STOMACH* 

The  muscular  mechanisms  by  means  of  which  the  stomach  is 
charged  with  food  and  in  turn  discharged,  small  portions  at  a  time, 
into  the  duodenum  have  been  described.  The  present  chapter  deals 
only  with  the  chemical  and  mechanical  changes  in  the  food  during 
its  stay  in  the  stomach  and  the  extent  to  which  the  products  of 
digestion  are  absorbed. 

The  Gastric  Glands. — The  tubular  glands  that  permeate  the 
mucous  membrane  of  the  stomach  throughout  its  entire  extent  differ 
in  their  histological  structure,  and  therefore  doubtless  in  their  secre- 
tion, in  different  parts  of  the  stomach.  Two,  sometimes  three,  kinds 
of  glands  are  distinguished, — the  pyloric,  fundic  (and  cardiac). 
Those  in  the  pyloric  part  of  the  stomach  (antrum  pylori)  are  char- 
acterized chiefly  by  the  fact  that  in  the  secreting  part  of  the  tubule 
only  one  type  of  gland  cell  is  found,  the  chief  or  peptic  cell,  while  in 
the  remainder  of  the  stomach,  but  particularly  hi  the  middle  or 
prepyloric  region  the  glands  (fundic  glands)  are  distinguished  by  the 
presence  of  two  types  of  cells, — the  chief  or  central  cells  and  the 
so-called  parietal  or  border  cells  (Fig.  293).  The  third  type,  the 
cardiac  glands,  is  found  around  the  cardia,  but  its  area  of  distribu- 
tion varies  in  different  animals,  and  its  histological  characteristics 
are  not  very  definite.*  There  seems  to  be  a  general  agreement  that 
the  central  cells  furnish  the  digestive  enzymes  of  the  stomach — 
pepsin  and  remain — and  the  parietal  cells  the  hydrochloric  acid. 
From  a  physiological  standpoint  it  is  important  to  remember  that 
the  parietal  cells  are  massed,  as  it  were,  in  the  glands  of  the  middle 
or  prepyloric  region  of  the  stomach,  that  they  are  scanty  in  the 
fundus,  and  absent  in  the  pyloric  region.  This  fact  is  indicated 
to  the  eye  by  the  deeper  red  or  brownish  color  of  the  mucous 
membrane  in  the  prepyloric  portion.  Grtitznerf  called  especial 
attention  to  this  relation,  and  in  connection  with  the  differences 
in  movements  of  these  two  parts  of  the  stomach  he  suggests  that 
normally  the  bulk  of  the  food  toward  the  fundus  becomes  impreg- 
nated first  with  pepsin;  then,  as  it  is  slowly  moved  into  the  pre- 
pyloric region,  the  acid  constituent  is  added.  The  pyloric  glands 
are  said  (Heidenhain)  to  secrete  an  alkaline  liquid  containing 
pepsin,  and,  according  to  Edkins  and  Starling,  they  form  a  sub- 
stance which  is  capable  of  acting  as  a  chemical  excitant  to  the 

*See  Haane,  "Archiv  f.  Anatomic/   1905,  1. 

t  Grutzner,  "Archiv  f .  die  gesammte  Physiologic,"  106,  463,  1905. 

774 


DIGESTION    AND    ABSORPTION    IN    THE    STOMACH. 


775 


glands  secreting  the  gastric  juice  (gastric  secretin  or  gastric  hor- 
mone).* 

Histological  Changes  in  the  Gastric  Glands  during  Secretion.— 
The  cells  of  the  gastric  glands,  especially  the  so-called  central  cells, 
show  distinct  changes  as  the  result  of  prolonged  activity.  Upon 
preserved  specimens,  taken  from  dogs  fed  at  intervals  of  twenty- 
four  hours,  Heidenhain  found  that  in  the  fasting  condition  the 
central  cells  were  large  and  clear,  that  during  the  first  six  hours  of 
digestion  the  central  cells  as  well  as  the  border  cells  increased  in 


and  A1,  during  hunger,  resting  condition  1 
ind  D,  the  second  stage  of  digestion,  showing 
or  central  cells. — (After  Heidenhain.) 

size,  but  that  in  a  second  period,  extending  from  the  sixth  to  the 
fifteenth  hour,  the  central  cells  became  gradually  smaller,  while 
the  parietal  cells  remained  large  or  even  increased  in  size.  After 
the  fifteenth  hour  the  central  cells  increased  in  size,  gradually 
passing  back  to  the  fasting  condition  (see  Fig.  293). 

Langleyf  has  succeeded  in  following  the  changes  in  a  more  satis- 
factory way  by  observations  made  directly  upon  the  living  gland. 

*See  Starling,  "Physiology  of  Secretion,"  Chicago,  1906,  and  Edkins, 
"Journal  of  Physiology,"  1906,  xxxiv.,  133. 
t  "Journal  of  Physiology,"  3,  269,  1880. 


776  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

He  finds  that  the  central  cells  in  the  fasting  stage  are  charged  with 
granules,  and  that  during  digestion  the  granules  are  dissolved,  dis- 
appearing first  from  the  base  of  the  cell,  which  then  becomes  filled 
with  a  non-granular  material.  Observations  similar  to  those  made 
upon  other  glands  demonstrate  that  these  granules  represent  in  all 
probability  a  preliminary  material  from  which  the  gastric  enzymes 
are  made  during  the  act  of  secretion.  The  granules,  therefore,  are 
sometimes  described  as  zymogen  granules. 

Means  of  Obtaining  the  Gastric  Secretion  and  its  Normal 
Composition. — The  secretion  of  the  gastric  membrane  is  formed  in 
the  minute  tubular  glands  scattered  over  its  surface.  As  there  is  no 
common  duct,  the  difficulty  of  obtaining  the  secretion  for  analysis 
or  experiment  is  considerable.  This  difficulty  has  been  overcome 
at  different  times  by  the  invention  of  special  methods. 

The  older  methods  used  for  obtaining  normal  gastric  juice  were 
very  unsatisfactory.  An  animal  was  made  to  swallow  a  clean 
sponge  to  which  a  string  was  attached  so  that  the  sponge  could 
afterward  be  removed  and  its  contents  be  squeezed  out;  or  it  was 
made  to  eat  some  indigestible  material,  to  start  the  secretion  of 
juice;  the  animal  was  then  killed  at  the  proper  time  and  the  con- 
tents of  its  stomach  were  collected. 

The  experiments  of  the  older  observers  on  gastric  digestion,  especially 
those  of  the  Abbe  Spallanzani  (1729-1799),  furnish  most  interesting  reading. 
Spallanzani,  not  content  with  making  experiments  on  numerous  animals 
(frogs,  birds,  mammals,  etc.)  had  the  courage  to  carry  out  a  great  many 
upon  himself.  He  swallowed  foods  of  various  kinds  and  in  various  conditions 
sewed  in  linen  bags  or  inclosed  in  perforated  wooden  tubes  which  in  turn 
were  covered  with  linen.  The  bags  and  tubes  were  subsequently  passed 
in  the  stools  and  were  examined  as  to  the  amount  and  nature  of  their  contents. 
He  seems  to  have  experienced  no  injury  from  his  experiments,  although 
normally  his  powers  of  digestion  were  quite  feeble.  As  proof  that  the  trit-. 
urating  power  of  the  stomach  is  not  very  great  he  calls  attention  to  the  fact 
that  some  of  the  wooden  tubes  were  made  very  thin,  so  that  the  slightest 
pressure  would  crush  them,  and  yet  they  were  voided  uninjured.  So  also 
he  found  that  cherries  and  grapes  when  swallowed  whole,  even  if  entirely 
ripe,  were  usually  passed  unbroken. 

A  better  method  of  obtaining  normal  juice  was  suggested  by  the 
famous  observations  of  Beaumont*  upon  Alexis  St.  Martin.  St. 
Martin,  by  the  premature  discharge  of  his  gun,  was  wounded  in  the 
abdomen  and  stomach.  On  healing,  a  fistulous  opening  remained  in 
the  abdominal  wall,  leading  into  the  stomach,  so  that  the  contents 
of  the  latter  could  be  inspected.  Beaumont  made  numerous  inter- 
esting and  most  valuable  observations  upon  his  patient.  Since  that 
time  it  has  become  customary  to  make  fistulous  openings  into  the 
ptomachs  of  dogs  whenever  it  is  necessary  to  have  the  normal  juice 
for  examination.  A  similar  surgical  procedure  is  followed  in  human 

*  Beaumont,  "The  Physiology  of  Digestion,"  1833;  second  edition,  1847. 
For  a  biographical  account  of  Beaumont,  see  Osier,  "Journal  of  the  American 
Medical  Association,"  November  15,  1902. 


DIGESTION    AND    ABSORPTION    IN    THE    STOMACH. 


777 


cases  in  whom  the  esophagus  has  been  occluded  by  an  accident  of 
one  kind  or  another,  usually  as  a  result  of  drinking  strong  lye.  In 
these  cases  a  fistulous  opening  is  established  through  the  abdominal 
wall  into  the  stomach.  Through  this  opening  the  individual  can 
be  fed  successfully,  and,  when  desired,  specimens  of  gastric  juice 
can  be  obtained.  The  study  of  these  exceptional  cases  has  added 
greatly  to  our  knowledge  of  the  functions  of  the  stomach.  Gastric 
juice  may  be  obtained  from  human  beings  also  in  cases  of  vomiting 
or  by  means  of  the  stomach-tube,  but  in  such  cases  it  is  necessarily 
more  or  less  diluted  or  mixed  With  food  and  cannot  be  used  for  exact 
analyses,  although  specimens  of  gastric  juice  obtained  by  these 
methods  are  employed  in  the  diagnosis  and  treatment  of  gastric 
troubles/ 

From  the  standpoint  of  experimental  investigation  a  very  im- 
portant addition  to  our  methods  was  made  by  Heidenhain.  This 
observer  showed  that  a  portion  of  the  stomach — the  fundic  end,  for 
instance,  or  the  pyloric  end — might  be  cut  away  from  the  rest  of  the 
organ  and  be  given  an 
artificial  opening  to  the 
exterior.  By  this  means 
the  secretion  of  an  isolated 
fundic  or  pyloric  sac  may 
be  obtained  and  examined 
as  to  its  quantity  and  prop- 
erties. The  method  was 
subsequently  improved  by 
Pawlow,  whose  important 
contributions  are  referred 
to  below.  Fig.  294  gives 
an  idea  of  the  operation  as 
made  by  Pawlow  to  isolate 
a  fundic  sac  with  its  blood 
and  nerve  supply  unin- 
jured. 

The  normal  gastric  se- 
cretion is  a  thin,  colorless 
or  nearly  colorless  liquid 
with  a  strong  acid  reaction  and  a  characteristic  odor.  Its  spe- 
cific gravity  varies,  but  it  is  never  great,  the  average  being  about 
1.002  to  1.003.  Upon  analysis  the  gastric  juice  is  found  to  contain 
some  protein,  some  mucin,  and  inorganic  salts,  but  the  essential 
constituents  are  an  acid  (HC1)  and  two  or  possibly  three  enzymes, 
pepsin,  rennin,  and  lipase.  According  to  Rosemann,*  the  secretion 
in  dogs  has  a  specific  gravity  of  1002  to  1004  and  contains  0.4277 
per  cent,  of  dry  material,  of  which  0. 1325  per  cent,  is  ash.  Analysis 
*  Rosemann,  "Archiv  f.  d.  ges.  Physiologic,"  118,  467,  1907. 


Fig.  294.— To  show  Pawlow's  operation  for 
making  an  isolated  fundic  sac  from  the  stomach: 
v,  Cavity  of  the  stomach;  «,  the  fundic  sac,  shut  off 
from  the  stomach  and  opening  at  the  abdominal 
wall,  a,  a;  6  indicates  the  line  of  sutures. — (Paw- 
low.} 


778  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION.       • 

of  the  ash  shows  that  it  contains  24  per  cent,  of  potassium,  19  per 
cent,  of  sodium,  and  0.18  per  cent,  of  calcium.  The  HC1  amounts 
to  0.55  per  cent.  This  author  states  that  in  one  animal  during  a 
secretion  lasting  3J  hours  about  5  gm.  of  chlorin  were  given  off  in 
the  secretion  in  the  form  of  chlorids,  an  amount  about  equal  to  that 
contained  in  the  entire  blood.  Carlson,*  from  his  studies  upon  a 
human  case  with  a  permanent  gastric  fistula,  gives  the  following 
figures  for  the  normal  secretion:  Average  specific  gravity,  1007; 
total  solids,  0.48  to  0.58  gm.  per  100  c.c.,  of  which  0.11  to  0.14  was 
organic  material;  total  nitrogen,  0.6  gm.  per  100  c.c.;  ammonia, 
2  to  3  mgm.  per  100  c.c.;  amino-acid  nitrogen,  3  to  9  mgm.  per  100 
c.c.;  average  acidity,  0.48  per  cent.,  or,  expressed  in  hydrogen-ion 
concentration  (Menten),  a  pH  of  0.92  to  1.13.  Gastric  juice  does 
not  give  a  coagulum  upon  boiling,  but  the  digestive  enzymes  are 
thereby  destroyed.  One  of  the  interesting  facts  about  this  secre- 
tion is  the  way  in  which  it  withstands  putrefaction.  It  may  be  kept 
for  a  long  time,  for  months  even,  without  becoming  putrid  and  with 
very  little  change,  if  any,  in  its  digestive  action  or  in  its  total  acidity. 
This  fact  shows  that  the  juice  possesses  antiseptic  properties,  and  it 
is  usually  supposed  that  the  presence  of  the  free  acid  accounts  for 
this  quality. 

The  Acid  of  Gastric  Juice. — The  nature  of  the  free  acid  in  gastric 
juice  was  formerly  the  subject  of  dispute,  some  claiming  that  the 
acidity  is  due  to  HC1,  since  this  acid  can  be  distilled  off  from  the  gas- 
tric juice,  others  contending  that  an  organic  acid,  lactic  acid,  is 
present  in  the  secretion.  All  recent  experiments  tend  to  prove  that 
the  acidity  is  due  to  HC1.  This  fact  was  first  demonstrated  satis- 
factorily by  the  analyses  of  Schmidt,  who  showed  that  if,  in  a  given 
specimen  of  gastric  juice,  the  chlorids  were  all  precipitated  by  silver 
nitrate  and  the  total  amount  of  chlorin  was  determined,  more  was 
found  than  could  be  held  in  combination  by  the  bases  present  in  the 
secretion.  Evidently,  some  of  the  chlorin  must  have  been  present 
in  combination  with  hydrogen  as  hydrochloric  acid.  Confirmatory 
evidence  of  one  kind  or  another  has  since  been  obtained.  The 
percentage  of  HC1  in  the  secretion  as  it  is  obtained  from  an  isolated 
fundic  sac  of  the  stomach  varies  around  0.5  per  cent.,  and  we  must 
suppose  that  this  figure  represents  the  concentration  of  acid  in  the 
juice  as  it  is  secreted.  When  the  contents  of  a  normal  stomach  are 
examined  during  digestion  the  acidity  is  said  to  be  much  lower, 
varying  around  0.2  per  cent,  as  a  maximum.  This  low  acidity  may 
be  accounted  for  in  part  by  dilution,  by  neutralization  from  the  al- 
kaline salts  of  the  saliva  or  the  gastric  mucosa,  or  by  combination 
with  the  protein  of  the  food,  but  Boldyreff  f  states  that  the  acidity 

*  For  summary  consult  Carlson,  "The  Control  of  Hunger  in  Health  and 
Disease,"  Chicago,  1916. 

t  Boldyreff,  "Quarterly  Journal  of  Exp.  Physiol.,  8,  1,  1914. 


DIGESTION    AND    ABSORPTION    IN    THE    STOMACH.  779 

is  reduced  mainly  by  a  regurgitation  of  the  alkaline  duodenal  con- 
tents which  occurs  at  periods  during  digestion.  He  considers  that 
this  regurgitation  is  a  self-regulating  mechanism  for  maintaining 
the  low  acidity  of  the  gastric  contents.  The  normal  occurrence  of 
regurgitation  during  gastric  digestion  is  confirmed  by  several  ob- 
servers. Clinicians  make  a  distinction  between  free  and  com- 
bined acid  in  the  gastric  secretion.  By  the  first  term  is  meant 
that  the  acid  exists  in  solution  as  in  so  much  water,  and  is,  therefore, 
largely  dissociated  with  the  production  of  a  corresponding  amount 
of  hydrogen  ions.  Under  the  second  term  is  included  the  acid 
that  is  combined  in  some  way  with  the  protein  material.  In 
this  form  the  acid  is  less  dissociated  and  the  acidity,  that  is  to  say, 
the  concentration  of  hydrogen  ions,  is  much  less.  Methods  have 
been  devised  for  estimating  the  total  acidity  and  the  free  and  com- 
bined acid.*  The  application  of  these  methods  has  shown  that 
after  a  protein  (meat)  diet  so-called  free  acid  may  not  appear  in 
the  gastric  contents  for  an  hour  or  more.  For  physiological  pur- 
poses it  is  preferable  to  abandon  the  use  of  the  terms  free  and 
combined  acid,  and  instead  to  express  the  degree  of  acidity  in  terms 
of  the  actual  hydrogen-ion  concentration.  This  factor  may  be  de- 
termined by  the  use  of  hydrogen  gas  electrodes,  the  electrometric 
method,  or  by  the  use  of  various  indicators  which  give  a  change 
of  color  at  different  concentrations  of  hydrogen  ions,  the  colori- 
metric  method.  Using  the  former  method,  Mentenf  reports  for 
the  normal  juice  as  secreted  a  concentration  in  hydrogen  ions 
varying  round  1  X  10"1,  or  a  hydrogen  exponent  of  pH  =  1  (see 
p.  417),  Using  the  colorimetric  method,  Michaelis  and  Davidsohn  t 
report  the  acidity  of  the  gastric  contents  after  a  test-meal  as  equal 
to  1.7  X  1(T2  (0.017). 

The  Origin  of  the  HCL— That  the  acid  of  the  gastric  juice  is  a 
mineral  acid  and  is  present  in  considerable  strength  is  a  remarkable 
fact  that  has  excited  much  interest.  Attempts  have  been  made  to 
ascertain  the  histological  elements  concerned  in  its  secretion  and 
the  nature  of  the  chemical  reaction  or  reactions  by  which  it  is  pro- 
duced. With  regard  to  the  first  point,  it  is  generally  believed  that 
the  parietal  cells  of  the  gastric  tubules  constitute  the  acid-secreting 
cells.  This  belief  is  founded  upon  the  general  fact  that  in  the 
regions  in  which  these  cells  are  chiefly  present — that  is,  the  middle 
region  of  the  stomach — the  secretion  is  distinctly  acid,  and  where 
they  are  absent  or  scanty  in  number  the  secretion  is  alkaline  or  less 
acid.  In  the  pyloric  region,  for  instance,  these  cells  are  lacking 
entirely  and  the  secretion  is  alkaline.  Moreover  microchemical 
reactions  seem  to  show  clearly  that  the  parietal  cells  are  particu- 

*  Simon,  "A  Manual  of  Clinical  Diagnosis." 
f  Menten,  "Journal  of  Biological  Chemistry/'  22,  341,  1915. 
t  Michaelis  and  Davidsohn,  "Zeitschrift  f.  exp.  Pathol.,"  8,  398,  1911;  also 
Boldyreff,  "Quarterly  Journal  of  Exp.  Physiol.,"  8, 1,  1914. 


780  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

larly  rich  in  chlorids,  and  this  fact  serves  to  connect  them  with 
the  production  of  the  acid.  It  seems  perfectly  evident  that  the 
HC1  must  be  formed  in  the  long  run  from  the  chlorids  of  the 
blood.  The  chief  chlorid  is  NaCl,  and  by  some  means  this  com- 
pound is  broken  up;  the  chlorin  is  combined  with  hydrogen,  and 
is  then  secreted  upon  the  free  surface  of  the  stomach  as  HC1. 
In  support  of  this  general  statement  it  has  been  shown  that  if  the 
chlorids  in  the  blood  are  reduced  by  removing  them  from  the  food 
for  a  sufficient  time  the  secretion  of  gastric  juice  no  longer  contains 
acid.  On  the  other  hand,  addition  of  NaBr  or  KI  to  the  food  may 
cause  the  formation  of  some  HBr  and  HI,  together  with  HC1  in 
the  gastric  juice.  Maly  has  suggested  that  acid  phosphates  may 
be  produced  in  the  first  instance,  and  then  by  reacting  with  the 
sodium  chlorid  may  give  hydrochloric  acid,  according  to  the  formula, 
NaH2PO4  +  NaCl  =  Na2HPO4  +  HC1.  Other  theories  have  been 
proposed,  but,  as  a  matter  of  fact,  no  explanation  of  the  details 
of  this  reaction  is  satisfactory.  Many  observers  have  attempted 
by  microchemical  methods  to  determine  the  exact  points  in  the 
gastric  glands  at  which  the  acid  is  formed.  Most  of  these  attempts 
have  given  results  which  have  been  difficult  to  interpret.  Harvey 
and  Bensley,*  by  making  use  of  dyes  (cyanimin  and  neutral  red) 
which  give  different  colors  in  neutral,  alkaline,  and  acid  media, 
state  that  the  free  acid  is  found  only  on  the  internal  surface  of  the 
stomach  or  in  the  neck  of  the  glands.  The  parietal  cells  themselves 
exhibit  an  alkaline  reaction.  These  observers  advance,  therefore, 
the  probable  hypothesis  that  the  parietal  cells  secrete  a  chlorid 
of  an  organic  base,  and  this  compound  in  some  way  yields  free 
hydrochloric  acid  only  after  it  reaches  the  mouth  of  the  gland. 
While  the  ultimate  source  of  the  chlorin  of  the  hydrochloric  acid 
is  to  be  found  in  the  neutral  chlorids  of  the  blood  (NaCl),  certain 
as  yet  unknown  intermediate  compounds  are  formed  within  the 
parietal  cells  from  which  the  acid  is  eventually  produced. 

The  Secretory  Nerves  of  the  Gastric  Glands. — Although  several 
facts  indicated  to  the  older  observers  that  the  secretion  of  gastric 
juice  is  under  the  control  of  nerve  fibers,  we  owe  the  actual  experi- 
mental demonstration  of  this  fact  to  Pawlow.f  He  demonstrated 
that  the  secretion  is  under  the  control  of  the  nervous  system  and  that 
the  secretory  fibers  are  contained  in  the  vagus.  Direct  stimulation 
of  the  peripheral  end  of  the  cut  vagus  causes  a  secretion  of  gastric 
juice  after  a  long  latent  period  of  several  minutes.  This  long  latency 
may  be  due  possibly  to  the  presence  in  the  vagus  of  inhibitory 
fibers  to  the  gland,  which,  being  stimulated  simultaneously  with  the 
secretory  fibers,  delay  the  action  of  the  latter.  Very  striking  proof 

*  Harvey  and  Bensley,  "Biological  Bulletin,"  23,  225,  1912. 
t  See  Pawlow,  "The  Work  of  the  Digestive  Glands,"  translated  by  Thomp- 
son, 1902. 


DIGESTION    AND    ABSORPTION    IN    THE    STOMACH.  781 

of  the  general  fact  that  the  secretion  is  due  to  the  action  of  vagus 
fibers  is  furnished  by  such  experiments  as  these :  Pawlow  divided  the 
esophagus  in  the  neck  and  brought  the  two  ends  to  the  skin  so  as  to 
make  separate  fistulous  openings  to  the  exterior.  Under  these  con- 
ditions, when  the  animal  ate  and  swallowed  food  it  was  discharged 
to  the  exterior  instead  of  entering  the  stomach.  The  animal  thus 
had  the  enjoyment  of  eating  without  actually  filling  the  stomach. 
Eating  in  this  style  forms  what  the  author  called  a  fictitious 
or  sham  meal  (Scheinfutterung) .  It  was  found  that  it  causes 
an  abundant  flow  of  gastric  juice  as  long  as  the  vagi  are  intact, 
but  has  no  effect  on  the  secretion  when  these  nerves  are  cut. 
Evidently,  therefore,  the  sensations  of  taste,  odor,  etc.,  developed 
during  the  mastication  and  swallowing  of  food,  set  up  reflexly 
a  stimulation  of  secretory  fibers  in  the  vagus.  Pawlow  desig- 
nates a  secretion  produced  in  this  way  as  a  psychical  secretion, 
— a  term  which  implies  that  the  reflex  must  be  attended  by 
conscious  sensations.  In  favorable  cases  the  fictitious  feeding  has 
been  continued  for  five  or  six  hours  and  a  large  amount  of  gastric 
juice  (700  c.c.)  has  been  collected  from  a  fistula,  although  no  food 
actually  entered  the  stomach.  It  is  important  to  note,  also,  that  a 
psychical  secretion,  once  started,  may  continue  for  a  long  time  after 
the  stimulus  (the  eating)  has  ceased.  Experiments  have  been  made 
upon  human  beings  under  similar  conditions.  Thus,  Hornborg* 
reports  the  case  of  a  boy  with  a  stricture  of  the  esophagus  and  a 
fistula  in  the  stomach.  Food  when  chewed  and  swallowed  did  not 
reach  the  stomach,  but  was  regurgitated;  it  caused,  nevertheless, 
an  active  psychical  secretion  in  the  empty  stomach. 

Normal  Mechanism  of  the  Secretion  of  the  Gastric  Juice. — 
It  has  usually  been  assumed  that  the  gastric  glands  are  quiescent 
whenjthe  stomach  is  empty  and  are  stimulated  to  activity  during  the 
eating  and  digestion  of  food.  According  to  the  results  published 
by  Carlson  f  this  view  is  not  wholly  correct  Even  in  the  period 
of  fasting  there  is  a  small  continuous  secretion  varying  from  2  to 
50  c.c.  per  hour.  But  during  the  act  of  eating  and  throughout  the 
period  of  gastric  digestion  the  rate  of  secretion  is  increased  greatly, 
reaching  a  flow  of  as  much  as  3.5  c.c.  per  minute.  The  modern  ex- 
planation of  the  origin,  maintenance,  and  regulation  of  this  flow  of 
secretion  is  due  chiefly  to  Pawlow.  Contrary  to  a  former  general  be- 
lief, he  showed  that  mechanical  stimulation  of  the  gastric  mucous  > 
membrane  has  no  effect  on  the  secretion  of  the  tubules.  This  factor 
may,  therefore,  be  eliminated.  In  an  ordinary  meal  the  secretion 
first  started  is  due  to  the  sensations  of  eating — that  is,  it  is  a  psych- 
ical secretion.  The  afferent  stimuli  originate  in  the  mouth  and 

*Hornborg,  " Skandinavisches  Archiv  f.  Physiologic,"  15,  209,  1904;  see 
also  Bickel,  "Verhandl.  Kongr.  f.  innere  Medizin,"  23,  491,  and  Carlson,  "The 
Control  of  Hunger  in  Health  and  Disease,"  Chicago,  1916. 

f  Carlson,  loc.  cit. 


782  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

nostrils;  the  efferent  path,  the  secretory  fibers,  is  through  the  vagus 
nerve.  This  reflex  insures  the  beginning  at  least  of  gastric  digestion, 
but  its  effect  is  supplemented  by  a  further  action  arising  in  the  stom- 
ach itself.  It  seems  that  some  foods  contain  substances  designated 
as  secretogogues,  that  are  able  to  cause  a  secretion  of  gastric  juice 
when  taken  into  the  stomach.  Thus,  meat  extracts,  meat  juices, 
soups,  etc.,  are  particularly  effective  in  this  respect;  milk  and  water 
cause  less  secretion.  In  other  foods  these  ready-formed  secreto- 
gogues are  lacking.  Certain  common  articles  of  food,  such  as 
bread  and  white  of  eggs,  have  no  effect  of  this  kind  at  all.  If  intro- 
duced into  the  stomach  of  a  dog  through  a  fistula  so  as  not  to  arouse 
a  psychical  secretion, — for  instance,  while  the  dog's  attention  is  di- 
verted or  while  he  is  sleeping, — they  cause  no  flow  of  gastric  juice 
and  are  not  digested.  If  such  articles  of  food  are  eaten,  however, 
they  cause  a  psychical  secretion,  and  when  this  has  acted  upon  the 
foods  some  products  of  their  digestion  in  turn  become  capable  of 
arousing  a  further  flow  of  gastric  juice.  The  steps  in  the  mechanism 
of  secretion  are,  therefore,  three:  (1)  The  psychical  secretion  or  ap- 
petite secretion;  (2)  the  secretion  from  secretogogues  contained  in 
the  food;  (3)  the  secretion  from  secretogogues  contained  in  the  prod- 
ucts of  digestion.  The  manner  in  which  the  secretogogues  act 
cannot  be  stated  positively.  Since  the  gastric  glands  possess 
secretory  nerve  fibers  the  first  explanation  to  suggest  itself  is 
that  the  secretogogues  by  acting  on  sensory  fibers  in  the  gastric 
mucous  membrane  reflexly  stimulate  the  secretory  fibers.  This 
explanation,  however,  is  rendered  untenable  by  the  fact  that  the 
effect  of  these  substances  is  obtained  after  complete  severance 
of  the  nervous  connections  of  the  stomach.  If,  therefore,  this 
so-called  chemical  secretion  is  produced  by  a  nervous  reflex,  the 
nerve  centers  concerned  must  lie  in  the  stomach  itself,  the  reflex 
must  take  place  through  the  intrinsic  ganglion  cells.  Another 
more  probable  explanation  has  been  offered.  Edkins  *  has  shown 
that  decoctions  of  the  pyloric  mucous  membrane,  made  by  boiling 
in  water,  acid  or  peptone  solutions,  when  injected  into  the  blood 
cause  a  marked  secretion  of  gastric  juice.  These  substances  when 
injected  alone  into  the  blood  cause  no  such  effect,  and  decoctions 
of  the  mucous  membrane  of  the  fundic  end  of  the  stomach  are 
without  action  on  the  gastric  secretion.  This  author  suggests, 
therefore,  that  the  secretogogues,  whether  preformed  in  the  food  or 
formed  during  digestion,  act  upon  the  pyloric  mucous  membrane 
and  form  a  substance  which  he  designates  as  gastrin  or  gastric  se- 
cretin,  and  this  substance  after  absorption  into  the  blood  is  carried 
to  the  gastric  glands  and  stimulates  them  to  secretion.  The  effect 
is,  therefore,  not  a  usual  nervous  reflex,  but  an  instance  of  the 
stimulation  of  one  organ  by  chemical  products  formed  in  another. 

*  Edkins,  "Journal  of  Physiology,"  1906,  xxxiv.,  p.  133. 


DIGESTION    AND    ABSORPTION    IN    THE    STOMACH. 


783 


Starling*  has  emphasized  the  fact  that  this  mode  of  control  is 
frequently  employed  in  the  body,  as  will  be  described  in  the 
following  pages  in  connection  with  the  pancreatic  secretion  and 
the  internal  secretions.  He  proposes  to  designate  such  sutn 
stances  by  the  general  term  of  hormones  (from  oppaw,  arouse 
or  excite).  Leaving  aside  for  the  moment  the  way  in  which 
the  secretogogues  excite  the  secretion  it  is  important  to  empha- 


Digestive 
power  in 
millimeters. 

Acidity  in 
percentage. 

Quantity  in 
cubic  centi- 
meters. 

MILK,       MEAT,      BREAD, 
600  c.c.    100  gms.   100  gms. 

10 

8 
6 
4 
2 
0 

0.576 
0.528 
0.480 
0.432 
0.384 
0.336 
0.288 
0.240 
0.192 
0.144 
0.096 
0.048 
0 

^ 

x 

\ 

s 

18 

16 
14 
12 
10 
8 
6 
4 
2 
0 

1 

1 

\ 

1 

\ 

\ 

1 

\ 

i 

lv 

1 

\ 

^ 

! 

\ 

\ 

\ 

x 

V 

/ 

mm^ 

=a 

r=S 

^ 

^ 

/ 

^ 

— 

7 

\ 

Hours 

/  Z34S6?89  WV1Z 

Quantity  of  secretion. 
Acidity. 
Digestive  power. 


Fig.  295. — Diagram  showing  the  variation  in  quantity  of  gastric  secretion  in  the  dog  after  a 
mixed  meal;  also  the  variations  in  acidity  and  in  digestive  power. — (After  Khigine.) 

size  the  fact  that  in  the  normal  secretion  of  gastric  juice,  that 
is  to  say,  in  the  secretion  which  takes  place  during  an  ordinary 
meal,  we  must  distinguish  between  a  nervous  secretion  due  to 
the  action  of  the  secretory  fibers  in  the  vagus,  and  a  chemical 
secretion  due  to  the  chemical  stimulation  of  the  secrotogogues  or 
of  the  hormones  produced  by  them. 

The  researches  of  Pawlow  and  his  co-workers  seem  also  to  in- 
dicate that  the  quantity  and  properties  of  the  secretion  vary  with 
the  character  of  the  food.  The  quantity  of  the  secretion  varies, 
also,  other  conditions  being  the  same,  with  the  amount  of  food  to 

*  Starling,  "Recent  Advances  in  the  Physiology  of  Digestion,"  1906. 


784  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

be  digested,  and,  so  far  as  the  psychical  or  appetite  secretion  is 
concerned,  with  the  palatableness  of  the  food.  The  apparatus 
is  adjusted  in  this  respect  to  work  economically.  Different 
kinds  of  food  produce  secretions  varying  not  only  as  regards 
quantity  but  also  in  their  acidity  and  digestive  action.  The 
secretion  produced  by  bread,  though  less  in  quantity  than  that 
caused  by  meat,  possesses  a  greater  digestive  action.  On  a 
given  diet  the  secretion  assumes  certain  characteristics,  and 
Pawlow  is  convinced  that  further  work  will  disclose  the  fact 
that  the  secretion  of  trie  stomach  is  not  caused  normally  by  general 
stimuli  all  affecting  it  alike,  but  by  specific  stimuli  contained  in  the 
food  or  produced  during  digestion,  whose  action  is  of  such  a  kind 
as  to  arouse  reflexly  the  secretion  best  adapted  to  the  food  ingested. 

One  of  the  curves,  showing  the  effect  of  a  mixed  diet  (milk,  600 
c.c.;  meat,  100  gms.;  bread,  100  gms.)  upon  the  gastric  secretion, 
as  determined  by  Pawlow's  method,  is  reproduced  in  Fig.  295.  It  will 
be  noticed  that  the  secretion  began  shortly  after  the  ingestion  of  the 
food  (seven  minutes),  and  increased  rapidly  to  a  maximum  that  was 
reached  in  two  hours.  After  the  second  hour  the  flow  decreased 
rapidly  and  nearly  uniformly  to  about  the  tenth  hour.  The  acidity 
rose  slightly  between  the  first  and  second  hours,  and  then  fell  gradu- 
ally. The  digestive  power  showed  an  increase  between  the  second 
and  third  hours. 

Nature  and  Properties  of  Pepsin. — Pepsin  is  a  typical  proteo- 
lytic  enzyme  that  exhibits  the  striking  peculiarity  of  acting  only  in 
acid  media;  hence  peptic  digestion  in  the  stomach  is  the  result  of 
the  combined  action  of  pepsin  and  hydrochloric  acid.  Pepsin  is 
influenced  in  its  action  by  temperature,  as  is  the  case  with  the  other 
enzymes;  low  temperatures  retard,  and  may  even  suspend  its 
activity,  while  high  temperatures  increase  it.  The  optimum  tem- 
perature is  stated  to  be  from  37°  to  40°  C.,  while  exposure  for  some 
time  to  80°  C.  results,  when  the  pepsin  is  in  a  moist  condition,  in  the 
total  destruction  of  the  enzyme.  Pepsin  may  be  extracted  from  the 
gastric  mucous  membrane  by  a  variety  of  methods  and  in  different 
degrees  of  purity  and  strength.  The  commercial  preparations  of 
pepsin  consist  usually  of  some  form  of  extract  of  the  gastric  mucous 
membrane  to  which  starch  or  sugar  of  milk  has  been  added.  Labora- 
tory preparations  are  made  conveniently  by  mincing  thoroughly 
the  mucous  membrane  and  then  extracting  for  a  long  time  with 
glycerin.  Glycerin  extracts,  if  not  too  much  diluted  with  water  or 
blood,  keep  for  an  indefinite  time.  Purer  preparations  of  pepsin 
have  been  made  by  what  is  known  as  "Briicke's  method/'  in  which 
the  mucous  membrane  is  minced  and  is  then  self-digested  with  a  5 
per  cent,  solution  of  phosphoric  acid.  The  phosphoric  acid  is  pre- 
cipitated by  the  addition  of  lime-water,  and  the  pepsin  is  carried 
down  in  the  flocculent  precipitate.  This  precipitate,  after  being 


DIGESTION    AND    ABSORPTION    IN    THE    STOMACH.  785 

washed,  is  carried  into  solution  by  dilute  hydrochloric  acid,  and  a 
solution  of  cholesterin  in  alcohol  and  ether  is  added:  The  cholesterin 
is  precipitated,  and,  as  before,  carries  down  with  it  the  pepsin.  This 
precipitate  is  collected,  carefully  washed,  and  then  treated  repeatedly 
with  ether,  which  dissolves  and  removes  the  cholesterin,  leaving  the 
pepsin  in  aqueous  solution.  This  method  is  interesting  not  only 
because  it  gives  a  pure  form  of  pepsin,  but  also  in  that  it  illustrates 
one  of  the  properties  of  enzymes — namely,  the  readiness  with  which 
they  are  adsorbed  by  precipitates  occurring  in  their  solutions. 

In  spite  of  much  work,  the  chemical  nature  of  pepsin  is  undeter- 
mined. Pekelharing*  has  prepared  pepsin  from  gastric  juice  by 
dialysis,  the  substance  precipitating  as  the  acid  is  dialyzed  off. 
The  precipitate  may  be  purified  by  repeated  resolutions  in  acid 
followed  by  dialysis.  As  prepared  by  this  method  pepsin  is  a 
substance  of  a  protein  nature  which  contains  sulphur  and  also 
some  chlorin,  but  no  phosphorus.  It  does  not  belong,  therefore, 
to  the  group  of  nucleoproteins.  Other  authors,  on  the  contrary, 
assert  that  active  preparations  of  pepsin  may  be  obtained  which 
give  no  protein  reactions,  although  they  contain  nitrogen. 

Pepsin  is  supposed  to  be  formed  in  the  central  cells  of  the  gastric 
tubules,  but  as  in  other  cases  it  is  present  in  the  cells  as  a  zymogen 
or  propepsin,  which  is  not  changed  to  the  active  pepsin  until  after 
secretion.  The  propepsin  may  be  extracted  readily  from  the  mucous 
membrane,  and,  since  it  is  known  that  the  zymogen  is  converted 
quickly  to  active  pepsin  by  the  action  of  acids,  it  is  evident  that  in 
the  normal  gastric  juice  the  existence  of  the  hydrochloric  acid 
insures  that  all  of  the  pepsin  shall  be  present  in  active  form.  There 
has  been  much  discussion  as  to  the  nature  of  the  secretion  of  the 
pyloric  glands.  Heidenhain  isolated  this  portion  of  the  stomach  and 
collected  its  secretion.  He  found  that  it  was  alkaline  and  contained 
pepsin.  Later  observers,  however,  still  continue  to  doubt  the  secre- 
tion of  a  true  pepsin  in  this  portion  of  the  stomach.  Glaessnerf 
states  that  propepsin  can  not  be  obtained  from  extracts  of  the  pyloric 
glands,  and  that  the  proteolytic  enzyme  that  can  be  shown  in  this 
portion  of  the  stomach  by  self-digestion  in  acid  or  alkaline  media  is 
not  a  true  gastric  pepsin.  The  possibility  that  a  special  secretin 
(hormone)  is  formed  in  the  pyloric  mucous  membrane  has  been 
referred  to  above  (p.  782).  From  the  description  of  the  events 
in  the  stomach  (p.  727)  it  would  seem  that  the  food  material  which 
is  churned  and  stirred  by  the  contractions  of  the  pyloric  musculature 
has  already  been  charged  with  pepsin  and  hydrochloric  acid  by  the 
glands  of  the  middle  and  fundic  regions  before  reaching  the 
ant  rum  pylori. 

Artificial  Gastric  Juice.— In  studying  peptic  digestion  it  is  not 

Pekelharing,  "Zeitschrift  f.  physiol.  Chemie,"  35,  8,  1902. 
t  Glaessner,  "Beitrage  zur  chem.  Physiol.  u.  Pathol.,"  1,  24,  1901. 
50 


786  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

necessary  for  all  purposes  to  establish  a  gastric  fistula.  The  active 
agents  of  the  normal  juice  are  pepsin  and  an  acid  of  a  proper  strength ; 
and,  as  the  pepsin  can  be  extracted  and  preserved  in  various  ways 
and  the  hydrochloric  acid  can  easily  be  made  of  the  proper  strength, 
an  artificial  juice  can  be  obtained  at  any  time  and  may  be  used  in 
place  of  the  normal  secretion  for  many  purposes.  In  laboratory  ex- 
periments it  is  customary  to  employ  a  glycerin  or  commercial  prep- 
aration of  the  gastric  mucous  membrane,  and  to  add  a  small  portion 
of  this  preparation  to  a  large  bulk  of  0.2  per  cent,  hydrochloric  acid. 
The  artificial  juice  thus  made,  when  kept  at  a  temperature  of  from 
37°  to  40°  C.,  will  digest  proteins  rapidly  if  the  preparation  of  pepsin 
is  a  good  one.  While  the  strength  of  the  acid  employed  is  generally 
from  0.2  to  0.3  per  cent.,  digestion  will  take  place  in  solutions  of 
greater  or  less  acidity.  Too  great  or  too  small  an  acidity,  however, 
will  retard  the  process;  that  is,  there  is  for  the  action  of  the  pepsin 
an  optimum  acidity  which,  according  to  the  experiments  of  Mich- 
aelis,*  is  represented  by  a  concentration  of  hydrogen  ions  of  about 
4  X  10'2  (0.04  n). 

The  Pepsin-hydrochloric  Acid  Digestion  of  Proteins. — It  has 
long  been  known  that  solid  proteins,  when  exposed  to  the  action  of  a 
normal  or  an  artificial  gastric  juice,  swell  up  and  eventually  pass 
into  solution.  The  soluble  protein  thus  formed  was  known  not  to  be 
coagulated  by  heat,  and  was  remarkable  also  for  being  more  diffus- 
ible than  other  forms  of  soluble  proteins.  This  end-product  of  diges- 
tion was  formerly  conceived  as  a  soluble  protein  with  properties 
fitting  it  for  rapid  absorption,  and  the  name  of  peptone  was  given  to 
it.  It  was  quickly  found,  however,  that  the  process  is  complicated— 
that  in  the  conversion  to  so-called  "peptone"  the  protein  under 
digestion  passes  through  a  number  of  intermediate  stages.  The  in- 
termediate products  were  partially  isolated  and  were  given  specific 
names,  such  as  acid-albumin,  parapeptone,  and  propeptone.  The 
present  conception  of  the  process  we  owe  chiefly  to  Kiihne.  This 
author  believed  that  the  protein  passes  through  three  general  stages 
before  reaching  the  final  condition  of  peptone.  This  view  is  indi- 
cated briefly  by  the  following  schema : 

Native   protein. 

Acid  albumin  (syntonin). 

Primary  proteoses  (protalbumoses). 

Secondary  proteoses  (deutero-albumoses). 

Peptone. 

The  first  step  is  the  conversion  of  the  protein  to  an  acid  albumin. 
This  change  may  be  considered  as  being  chiefly  an  effect  of  the  hy- 
drochloric acid,  although  in  some  way  the  combined  action  of  the 
pepsin-hydrochloric  acid  compound  is  more  effective  than  a  solution 
of  the  acid  alone  of  the  same  strength.  Like  the  acid  albumins 

*  Michaelis  and  Mendelssohn,  "Biochemische  Zeitschrift,"  65,  1,  1914. 


DIGESTION    AND    ABSORPTION    IN    THE    STOMACH.  787 

(metaproteins)  in  general  (see  Appendix),  the  syntonin  is  readily 
precipitated  on  neutralization.  In  the  beginning  of  peptic  diges- 
tion, therefore,  if  the  solution  is  neutralized  with  dilute  alkali, 
an  abundant  precipitate  of  syntonin  occurs.  Later  on  in  the 
digestion,  neutralization  gives  no  such  effect — the  syntonin 
has  all  passed  to  a  further  stage  of  digestion.  Under  the  in- 
fluence of  the  pepsin  the  syntonin  undergoes  hydrolysis,  with 
the  production  of  a  number  of  bodies  which,  as  a  group,  are 
designated  as  primary  proteoses  or  protalbumoses.*  Although 
several  members  of  this  group  have  been  isolated  and  given 
separate  names,  so  much  doubt  prevails  as  to  the  chemical  individ- 
uality of  these  substances  that  it  is  best  perhaps  to  regard  them  as  a 
group  of  compounds  which  under  the  continued  influence  of  the 
pepsin  undergo  still  further  hydrolysis  with  the  formation  of  secon- 
dary proteoses  or  deutero-albumoses.  As  compared  with  the  primary 
proteoses,  the  secondary  ones  are  distinguished  by  a  greater  solu- 
bility ;  they  require  a  stronger  saturation  with  neutral  salts  to  precipi- 
tate them.  (See  Appendix.)  The  secondary  proteoses  undergo  still 
further  hydrolysis,  with  the  production  of  peptone,  or  perhaps  it 
would  be  better  to  say  peptones.  The  peptones  show  still  greater 
solubility,  and,  in  fact,  peptone,  in  Kuhne's  sense,  is  that  compound 
or  group  of  compounds  formed  in  peptic  digestion  which,  while  still 
showing  protein  reactions  (biuret  reaction),  is  not  coagulated  by 
heat  nor  precipitated  when  its  solutions  are  completely  saturated 
with  ammonium  sulphate.  According  to  the  schema  and  descrip- 
tion given  above,  the  several  stages  in  peptic  digestion  are  repre- 
sented as  following  in  sequence.  It  should  be  stated,  however, 
that  many  authors  consider  that  even  in  the  beginning  of  the 
digestion  the  protein  molecule  may  be  split  into  several  complexes, 
and  that  some  of  the  end-products  may  be  formed  very  early  in 
the  action.  The  end-result  of  the  action  of  the  pepsin  in  the 
stomach  is  the  conversion  of  more  or  less  of  the  protein  of  the 
food  into  the  simpler  and  more  soluble  peptones  and  proteoses. 
The  action  of  the  enzyme  is  preparatory  to  the  more  complete 
hydrolysis  that  takes  place  in  the  intestine  under  the  influence  of 
the  trypsin  and  erepsin,  for,  as  we  shall  see,  the  protein  of  the  food 
is  not  absorbed  into  the  blood  as  peptones,  but  suffers  first  a  further 
hydrolysis  to  amino-acids  and  peptids.  While  the  pepsin  is,  there- 
fore, a  relatively  weak  proteolytic  enzyme,  it  plays  an  important 
role  in  initiating  the  splitting  up  of  the  protein  molecule,  and  its 
value  in  this  respect  is  increased  by  the  fact  that  it  is  adapted  to 
act  upon  proteins  of  all  kinds  and  bring  them  to  a  stage  suitable  for 

*,The  products  intermedfate  between  the  original  protein  and  the  pep- 
tone are  described  in  general  as  albumoses  or  as  proteoses,  according  as  one 
takes  the  term  protein  or  albumin  as  the  generic  name  for  the  original  sub- 
stance. The  term  protein  is  generally  used  in  English ;  hence,  the  intermedi- 
ate products  are  more  appropriately  designated  as  proteoses. 


788  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

the  more  complete  action  of  the  proteolytic  enzymes  of  the  intes- 
tinal secretion. 

In  judging  the  digestive  action  of  any  given  specimen  of  natural 
or  artificial  gastric  juice  it  is  customary  to  measure  the  rapidity 
with  which  an  insoluble  protein  is  converted  into  a  soluble  form. 
The  method  most  commonly  employed  is  that  devised  in  Pawlow's 
laboratory  by  Mett.  The  Mett  test  is  made  by  sucking  white  of  egg 
into  a  thin-walled  glass  tube  having  an  internal  diameter  of  1  to  2 
mms.  The  egg-albumin  is  coagulated  in  the  tube  by  immersing  it  for 
five  minutes  in  water  at  95°  C.  After  some  time  the  tube  is  cut  into 
lengths  of  10  to  15  mms.  and  these  are  used  to  test  the  digestive  action 
or  amount  of  pepsin.  One  or  more  of  the  tubes  are  placed  in  the 
solution  to  be  measured  and  kept  for  ten  hours  at  body  temperature. 
The  digestive  power  is  measured  in  terms  of  the  length  in  millimeters 
of  the  column  of  egg-albumin  that  is  dissolved.  The  relative  amounts 
of  pepsin  in  solutions  compared  in  this  way  are  determined  by  the 
law  of  Schiitz,  according  to  which  the  digestive  power  is  proportional 
to  the  square  root  of  the  amount  of  pepsin.  If  in  two  specimens  of 
gastric  juice  the  number  of  millimeters  of  egg  albumin  digested 
was  in  one  case  two  and  in  the  other  three,  the  pepsin  in  the  two 
solutions  would  be  as  the  squares  of  the  numbers,  as  4  to  9. 

The  Rennin  Enzyme  (Rennet,  Chymosin). — The  property 
possessed  by  the  mucous  membrane  of  the  calf's  stomach  of  curdling 
milk  has  been  known  from  remote  times,  and  has  been  utilized  in  the 
manufacture  of  cheese  and  curds.  This  action  takes  place  with 
remarkable  rapidity  under  favorable  conditions,  a  large  mass  of  milk 
setting  to  a  firm  coagulum  within  a  very  brief  time.  It  has  been 
shown  that  this  effect  is  due  to  an  enzyme — rennin  or  rennet.  The 
rennin.  like  the  pepsin,  is  supposed  to  be  formed  in  the  chief  cells  of 
the  gastric  tubules  and  to  be  present  in  the  glands  in  a  zymogen 
form,  the  prorennin  or  prochymosin,  which  after  secretion  is  con- 
verted to  the  active  enzyme.  This  conversion  takes  place  very 
readily  under  the  influence  of  acid.  Rennin  (or  its  zymogen)  may  be 
obtained  easily  from  the  mucous  membrane  of  the  stomach  (with 
the  exception  of  the  pyloric  end)  by  extracting  with  glycerin  or  water 
or  by  digesting  with  dilute  acid.  Good  extracts  of  rennin  cause 
the  milk  to  clot  with  great  rapidity  at  a  temperature  of  40°  C.;  the 
milk  (cows'  milk),  if  undisturbed,  sets  at  first  into  a  solid  clot,  which 
afterward  shrinks  and  presses  out  a  clear,  yellowish  liquid — the 
whey.  With  human  milk  the  curd  is  much  less  firm,  and  takes  the 
form  of  loose  flocculi.  The  whole  process  resembles  much  the  clotting 
of  blood.  The  rapidity  of  clotting  is  said  to  vary  inversely  as  the 
amount  of  rennin,  or,  in  other  words,  the  product  of  the  amount  >of 
rennin  and  the  time  necessary  for  clotting  is  a  constant.  The 
curdling  of  the  milk  involves  two  apparently  independent  proc- 
First,  the  rennin  acts  upon  the  casein  of  the  milk  and  converts 


DIGESTION    AND    ABSORPTION    IN    THE    STOMACH.  789 

it  into  a  substance  known  as  paracasein.  The  paracasein  then 
reacts  with  the  calcium  salts  of  the  milk,  forming  an  insoluble 
protein,  which  constitutes  the  curd  or  coagulum.  According 
to  this  view,  the  enzyme  does  not  cause  clotting  directly.*  What 
takes  place  when  the  casein  is  changed  to  paracasein  is  not  under- 
stood. Hammarsten  originally  regarded  the  change  as  a  cleavage 
process,  and  this  view  is  still  supported  by  some  authors, f  although 
denied  by  others.  Others  have  supposed  that  a  transformation  or 
rearrangement  of  molecular  structure  occurs.  Indeed,  the  differ- 
ences in  properties  between  Casein  and  paracasein  are  not  great, 
the  most  marked  difference  being  that  the  latter  in  the  presence  of 
calcium  salts  gives  an  insoluble  coagulum.  If  soluble  calcium  salts 
are  removed  from  milk  by  the  addition  of  oxalate  solutions,  it  does 
not  curdle  upon  the  addition  of  rennin.  Addition  of  lime  salts  re- 
stores this  property.  It  should  be  added  that  casein  is  also  pre- 
cipitated from  milk  by  the  addition  of  an  excess  of  acid.  The 
curdling  of  sour  milk  in  the  formation  of  bonnyclabber  is  a  well- 
known  illustration  of  this  fact.  When  milk  stands  for  some  time 
the  action  of  bacteria  upon  the  milk-sugar  leads  to  the  formation 
of  lactic  acid,  and  when  this  acid  reaches  a  certain  concentration 
it  causes  the  precipitation  of  the  casein. 

So  far  as  our  positive  knowledge  goes,  the  action  of  rennin  is 
confined  to  milk.  Casein  is  the  chief  protein  constituent  of  milk, 
and  has,  therefore,  an  important  nutritive  value.  It  is  interesting 
to  find  that  before  its  peptic  digestion  begins  the  casein  is  acted 
upon  by  an  altogether  different  enzyme.  The  value  of  the  curdling 
action  is  not  at  once  apparent,  but  we  may  suppose  that  casein  is 
more  easily  digested  under  the  conditions  that  exist  in  the  body 
after  it  has  been  brought  into  a  solid  form,  or,  perhaps,  the  coagu- 
lation of  the  casein  ensures  that  it  will  be  retained  in  the  stomach 
and  be  submitted  to  gastric  digestion,  instead  of  being  ejected 
promptly  into  the  duodenum,  as  happens  with  liquid  material. 
The  action  of  rennin  goes  no  further  than  the  curdling;  the  diges- 
tion of  the  curd  is  carried  on  by  the  pepsin,  and  later,  in  the  intes- 
tines, by  the  trypsin,  as  in  the  case  of  other  proteins.^ 

Rennin  is  found  elsewhere  than  in  the  gastric  mucosa.  It  has  been 
described  in  the  pancreatic  juice,  in  the  testis,  and  in  many  other  organs 
as  well  as  in  the  tissues  of  many  plants.  In  fact,  wherever  proteolytic  enzymes 
are  found  there  also  some  evidence  of  a  curdling  action  on  milk  may  be  ob- 
tained. For  this  reason  some  observers  §  have  taken  the  view  that  the  milk 
coagulation  is  not  due  to  a  specific  ferment,  but  is  an  action  of  the  pepsin  itself. 
That  is,  the  proteolytic  enzyme  is  capable  of  causing  the  change  from  casein 
to  paracasein  as  well  as  the  hydrolysis  of  the  protein.  This  view  is  opposed  to 
the  prevalent  opinion  regarding  the  specificity  of  enzyme  actions,  and  is  con- 

*  See  Bang,  "  Skandinavisches  Archiv  f.  Physiologic,"  25,  105,  1911. 
t  Bosworth  and  Van  Slyke,  "Journal  of  Biological  Chemistry,"  19,  67, 1914. 
j  For  references  to  very  abundant  literature,  consult  Oppenheimer,  loc.  cit. 
§  See  Pawlow  and  Parastschuk,  "Zeitschrift  f.  physiol.  Chemie,"  42  415 
1904:  Burge,  "American  Journal  of  Physiology,"  29,  330,  1912. 


790  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

tradicted  by  a  number  of  observers.  Burge,  for  example,  reports  that  if  a 
solution  showing  both  peptic  and  rennetic  action  is  submitted  to  the  action  of 
an  electric  current  the  peptic  power  is  destroyed  completely  in  a  certain  time, 
while  the  rennetic  action  remains  in  full  force. 

Another  interesting  fact  concerning  rennin  is  that  when  injected  into  an 
animal  it  causes  the  formation  of  a  specific  antibody  known  as  antirennin, 
which  may  be  detected  in  the  blood.  This  antirennin  added  to  milk  prevents 
its  curdling  by  rennin,  giving  a  result,  therefore,  similar  to  the  reaction  between 
toxins  and  antitoxins. 

The  Digestive  Changes  Undergone  by  the  Food  in  the 
Stomach. — In  addition  to  the  pepsin  and  rennin  various  observers 
have  described  other  enzymes  in  the  gastric  juice  or  gastric  mem- 
brane, but  the  evidence  at  hand  is  uncertain  regarding  these 
latter.  As  was  said  above,  it  is  probable  that  the  ptyalin 
swallowed  with  the  food  continues  to  exert  its  action  upon  the 
starchy  material  in  the  fundus  for  a  long  time,  so  that  in  this  way 
the  starch  digestion  in  the  stomach  may  be  important.  Regarding 
the  fats,  it  is  usually  believed  that  they  undergo  no  truly  digestive 
change  in  the  stomach.  They  are  set  free  from  their  intimate 
mixture  with  other  food  stuffs  by  the  dissolving  action  of  the  gas- 
tric juice  upon  proteins,  they  are  liquefied  by  the  heat  of  the  body, 
and  they  are  disseminated  through  the  chyme  in  a  coarse  emulsion 
by  the  movements  of  the  stomach.  In  this  way  they  are  mechan- 
ically prepared  so  that  the  subsequent  action  of  the  pancreatic 
juice  is  much  favored.  Some  observers*  state  that  the  gastric 
juice  does  normally  contain  a  lipase  capable  of  causing  hydrolytic 
cleavage  of  the  neutral  fat  into  fatty  acid  and  glycerin.  It  would 
appear,  however,  that  this  lipase  is  readily  destroyed  by  an  acidity 
of  0.2  per  cent.  HC1,  so  that  if  it  is  of  functional  importance  in 
gastric  digestion  its  action,  like  that  of  the  ptyalin,  must  be  con- 
fined to  the  early  period  of  digestion  before  the  contents  of  the. 
stomach  have  reached  their  normal  acidity.  Regarding  the  proteins, 
the  practical  point  of  interest  is  as  to  how  far  they  are  digested  dur- 
ing their  stay  in  the  stomach.  It  seems  probable  that  this  question 
does  not  admit  of  a  categorical  answer — that  is,  the  extent  of  the 
digestion  varies  under  different  circumstances;  with  the  consist- 
ency of  the  food,  the  duration  of  its  stay  in  the  stomach,  etc.  In 
some  experiments  reported  by  Tobler  it  is  stated  that  48  per  cent, 
of  a  given  amount  of  protein  passed  through  the  pylorus  as  pep- 
tones or  proteoses,  about  20  per  cent,  entered  the  intestine  un- 
digested, and  20  to  30  per  cent,  was  absorbed  from  the  stomach. 
In  the  liquid  material  (chyme)  forced  through  the  pylorus  into 
the  duodenum  one  may  find  unchanged  proteins,  primary  or 
secondary  proteoses,  peptones,  or,  possibly,  cleavage  products  be- 
yond this  stage.  It  is  stated,  however,  that  most  of  the  material 
is  in  the  form  of  proteoses  (London).  The  true  value  of  peptic 
digestion  is  not  so  much  in  its  own  action  as  in  its  combined  action 
*  Hall  and  Keeton,  "Journal  of  Biological  Chemistry,"  1917, 32, 127. 


DIGESTION    AND    ABSORPTION    IN   THE    STOMACH.  791 

with  the  trypsin,  or  the  trypsin  and  erepsin  found  in  the  intestine. 
The  preliminary  digestion  in  the  stomach  is  important  as  regards 
the  protein  foods  from  several  standpoints :  First,  in  the  matter  of 
mechanical  preparation  of  the  food  and  its  discharge  in  convenient 
quantities  easily  handled  by  the  duodenum.  Second,  in  the  more 
or  less  complete  hydrolysis  to  peptones  and  proteoses,  whereby 
the  subsequent  action  of  the  proteolytic  enzymes  of  the  intestine 
must  be  greatly  accelerated.  Indeed,  in  some  cases,  this  prelimi- 
nary action  of  the  pepsin-hydrochloric  acid  may  be  absolutely  neces- 
sary. Native  proteins,  such  as  serum-albumin,  are  not  acted  upon 
by  trypsin,  but  if  submitted  to  pepsin-hydrochloric  acid  they  are 
quickly  digested  by  this  enzyme.  These  and  other  facts  seem  to 
indicate  that  the  peptic  digestion  is  not  so  much  an  end  in  itself  as  a 
preparation  for  subsequent  intestinal  digestion.  The  stomach, 
therefore,  may  be  removed  without  a  fatal  result.  Several  cases 
are  on  record  in  which  the  stomach  was  practically  removed  by 
surgical  operation,  the  esophagus  being  stitched  to  the  duodenum.* 
The  animals  did  well  and  seemed  perfectly  normal,  although  special 
precautions  were  necessary  in  the  matter  of  feeding. 

Absorption  in  the  Stomach. — In  the  stomach  it  is  possible  that 
there  may  be  absorption  of  the  following  substances:  Water,  salts; 
sugars  and  dextrins  that  may  have  been  formed  in  salivary  digestion 
from  starch,  or  that  may  have  been  eaten  as  such;  the  proteoses  and 
peptones  formed  in  the  peptic  digestion  of  proteins  or  albuminoids. 
In  addition,  absorption  of  soluble  or  liquid  substances — drugs, 
alcohol,  etc.,  that  have  been  swallowed — may  occur.  It  was  formerly 
assumed,  without  definite  proof,  that  the  stomach  absorbs  easily 
such  things  as  water,  salts,  sugars,  and  peptones.  Actual  experi- 
ments, however,  made,  under  conditions  as  nearly  normal  as  possible, 
show,  upon  the  whole,  that  absorption  does  not  take  place  readily 
in  the  stomach — certainly  nothing  like  so  easily  as  in  the  intestine. 
The  methods  made  use  of  in  these  experiments  have  varied,  but  the 
most  interesting  results  have  been  obtained  by  establishing  a  fistula 
of  the  duodenum  just  beyond  the  pylorus,  f  After  establishing  this 
fistula  food  may  be  given  to  the  animal  and  the  contents  of  the 
stomach  as  they  pass  out  through  the  pyloric  opening  may  be 
caught  and  examined. 

Water. — Experiments  of  the  character  just  described  show  that 
water  when  taken  alone  is  practically  not  absorbed  at  all  in  the 
stomach.  Von  Mering's  experiments  especially  show  that  as  soon 
as  water  is  introduced  into  the  stomach  it  begins  to  pass  into  the 

*  Ludwig  and  Ogata,  "Archiv  f.  Physiologie,"  1883,  p.  89;  Carvallo  and 
Pachon,  "Archives  de  physiologie  norm,  et  path.,"  1894,  p.  106. 

t  Compare  von  Mering,  "Verhandl.  des  Congresses  f.  innere  Med.,"  12, 
471,  1893;  Edkins,  "Journal  of  Physiology,"  13,  445,  1892;  Brandl,  "Zeit- 
schrift  f.  Biologic,"  29,  277,  1892;  London,  "Zeitschrift  f.  physiol.  Chemie," 
62,  446,  1909. 


792  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

intestine,  being  forced  out  in  a  series  of  spurts  by  the  contractions  of 
the  stomach.  Within  a  comparatively  short  time  practically  all 
the  water  can  be  recovered  in  this  way,  none  or  very  little  having 
been  absorbed  in  the  stomach.  For  example,  in  a  large  dog  with  a 
fistula  in  the  duodenum,  500  c.c.  of  water  were  given  through  the 
mouth.  Within  twenty-five  minutes  495  c.c.  had  been  forced  out  of 
the  stomach  through  the  duodenal  fistula.  This  result  is  not 
true  for  all  liquids ;  alcohol,  for  example,  is  absorbed  readily. 

Salts. — The  absorption  of  salts  from  the  stomach  has  not  been 
investigated  thoroughly.  According  to  Brandl,  sodium  iodid  is 
absorbed  very  slowly  or  not  at  all  in  dilute  solutions.  Not  until  its 
solutions  reach  a  concentration  of  3  per  cent,  or  more  does  its  absorp- 
tion become  important.  This  result,  if  applicable  to  all  the  soluble 
inorganic  salts,  would  indicate  that  under  ordinary  conditions  they 
are  practically  not  absorbed  in  the  stomach,  since  it  can  not  be  sup- 
posed that  they  are  normally  swallowed  in  solutions  so  concentrated 
as  3  per  cent.  In  the  same  direction  Meltzer  reports  that  solutions 
of  strychnin  are  absorbed  with  difficulty  from  the  stomach  as  com- 
pared with  the  intestines,  rectum,  or  even  the  pharynx.  It  is  said 
that  the  absorption  of  sodium  iodid  is  very  much  facilitated  by 
the  use  of  condiments,  such  as  mustard  and  pepper,  or  alcohol, 
which  act  either  by  causing  a  greater  congestion  of  the  mucous 
membrane  or  perhaps  by  directly  stimulating  the  epithelial  cells. 

Sugars  and  Peptones. — In  regard  to  the  sugars  the  experiments 
of  von  Mering  and  Brandl  indicate  that  while  absorption  takes 
place  it  is  not  rapid  nor  marked  unless  the  solutions  are  quite 
concentrated  (5  per  cent.) ,  and  we  may  infer,  therefore,  that  in  an 
ordinary  meal  the  sugar  formed  from  the  starchy  foods  by  the 
action  of  the  ptyalin  is  passed  on  to  the  intestine  for  further  diges- 
tion and  absorption.  Whether  or  not  any  of  the  digested  proteins 
are  absorbed  from  the  stomach  has  been  and  still  is  a  matter  of 
controversy.  Some  of  the  older  experimenters  stated  that  as 
much  as  20  to  30  per  cent,  of  the  protein  of  a  meal  might  be 
absorbed  in  the  stomach,  but  the  results  of  the  more  recent  work, 
on  the  contrary,  indicate  that  little  or  no  absorption  takes  place 
under  normal  conditions.*  When  a  definite  amount  of  protein  was 
introduced  into  the  stomach  of  an  experimental  animal  it  could 
all  be  recovered,  as  estimated  by  nitrogen  determinations,  from  a 
duodenal  fistula. 

Fats. — As  we  have  seen,  fats  probably  undergo  no  digestive 
changes  in  the  stomach.  The  processes  of  saponification  and  emul- 
sification  are  supposed  to  be  preliminary  steps  to  absorption,  and 
these  processes  take  place  usually  after  the  fats  have  reached  the 
small  intestine. 

*  London,  loc.  tit. 


CHAPTER  XLIII. 
DIGESTION  AND  ABSORPTION  IN  THE  INTESTINES. 

The  food  undergoes  its  most  profound  digestive  changes  in  the 
intestines,  and  here  also  the  products  of  digestion  are  mainly  ab- 
sorbed. The  intestinal  digestion  begins  in  the  duodenum,  and  is  largely 
completed  by  the  time  that  the  food  arrives  at  the  ileocecal  valve. 
It  is  effected  through  the  combined  action  of  three  secretions, — the 
pancreatic  juice,  the  secretion  from  the  intestinal  glands  (succus 
entericus),  and  the  bile.  These  secretions  are  mixed  with  the  food 
from  the  duodenum  on,  so  that  their  action  proceeds  simultaneously. 
For  purposes  of  description  it  is  necessary  to  speak  of  each  more  or 
less  separately. 

The  Pancreas. — The  pancreas  forms  a  long,  narrow  gland  reach- 
ing from  the  spleen  to  the  curvature  of  the  duodenum.  Its  main 
duct  in  man  (duct  of  Wirsung)  opens  into  the  duodenum,  together 
with  the  .common  bile-duct,  about  8  to  10  cms.  beyond  the  pylorus. 
The  points  at  which  the  duct  or  ducts  of  the  pancreas  enter  the 
intestine  vary  somewhat  in  different  mammals.  In  the  dog  there  are 
two  chief  ducts,  one  opening,  together  with  the  bile-duct,  about  3  to 
5  cm.  below  the  pylorus,  while  a  second  enters  the  duodenum  some 
3  to  5  cms.  farther  down.  In  rabbits  the  principal  pancreatic  duct 
opens  separately  into  the  duodenum  about  35  cms.  below  the  opening 
of  the  bile-duct.  The  pancreas  is  a  compound  tubular  gland  like 
the  salivary  glands.  The  cells  lining  the  secreting  portion  of  the 
tubules,  the  alveoli,  belong  to  the  serous  or  albuminous  type.  They 
are  characterized  by  the  fact  that  the  outer  portion  of  each  cell  is 
composed  of  a  clear,  non-granular  material  which  stains  readily, 
while  the  inner  portion,  the  portion  facing  the  lumen,  contains 
numerous  granules.  Histological  study  of  the  gland  after  active 
secretion,  as  compared  with  the  resting  state,  has  shown  very  con- 
clusively that  these  granules  represent  a  preparatory  material  for 
secretion.  As  the  secretion  proceeds  the  granules  are  dissolved 
and  discharged  into  the  lumen,  while  during  the  periods  of  rest  new 
granules  are  formed  by  metabolic  processes  at  the  expense,  appar- 
ently, of  the  non-granular  material  in  the  basal  portion  of  the  cell. 
(Heidenhain,  Kiihne,  Lea).  The  histological  picture  of  secretion 
is  in  general  the  same  in  this  as  in  the  salivary  and  gastric  glands, 
only  somewhat  more  distinctly  shown.  On  the  supposition  that  the 
granules  constitute  an  antecedent  material  from  which  the  enzymes 

793 


794  PHYSIOLOGY  OF  DIGESTION  AND  SECRETION. 

of  the  secretion  are  formed  they  are  frequently  designated  as  zy mo- 
gen  granules.  The  pancreas  contains  also  certain  peculiar  groups  of 
cells,  the  islands  (or  bodies)  of  Langerhans.  These  cells  probably 
have  nothing  to  do  with  the  digestive  activity  of  the  pancreas. 
Their  supposed  function  is  referred  to  in  the  sections  on  Internal 
Secretions  and  Nutrition. 

Composition  of  the  Secretion. — The  pancreatic  secretion  is  an 
alkaline  liquid  which  in  some  animals  is  thin  and  limpid,  in  others 
thick  and  glairy.  The  secretion  in  man  belongs  to  the  former 
type;  it  is  described  as  water-clear  and  as  having  a  specific  gravity  of 
1.0075.  The  secretion  may  be  collected  by  opening  the  abdomen 
and  inserting  a  cannula  directly  into  the  duct,  or  a  permanent 
fistula  may  be  made  by  the  method  of  Pawlow.  This  method, 
applicable  to  the  dog,  consists  in  cutting  out  a  small  portion  of 
the  duodenum  where  the  pancreatic  duct  opens  and  then  suturing 
this  piece,  the  mucous  membrane  outward,  into  the  abdominal 
wall.  The  secretion  in  this  case  pours  out  upon  the  exterior  and  may 
be  collected.  The  animal,  however,  suffers  nutritive  disturbances 
from  the  loss  of  the  secretion,  and  requires  careful  dieting  and  atten- 
tion. The  secretion  of  the  human  pancreas  has  been  collected  in 
several  cases  in  which  it  was  necessary  to  drain  off  the  pancreatic 
juice  to  the  exterior.  From  the  observations  made  in  one  case*  it 
appears  that  the  secretion  in  man  is  quite  abundant,  amount- 
ing to  500  to  800  c.c.  per  day.  In  the  cow  (Delezenne)  from  1 J  to  2 
liters  may  be  collected  in  the  course  of  a  day.  The  secretion  pos- 
sesses a  strong  alkaline  reaction,  due  to  the  presence  of  sodium 
carbonate;  it  also  contains  a  small  amount  of  coagulable  protein 
and  a  number  of  organic  substances  in  traces.  The  important 
constituents,  however,  are  three  enzymes  or  their  zymogens,— 
namely,  trypsin,  a  proteolytic  enzyme;  pancreatic  diastase  (amyl- 
ase),  an  amylolytic  enzyme;  and  lipase  (steapsin),  a  lipolytic 
enzyme.  Some  authors  state,  also,  that  the  secretion  contains  a 
rennin  enzyme.  Glaessner  reports  that  he  got  no  evidence  of  this 
last  enzyme  in  human  pancreatic  juice. 

Secretory  Nerve  Fibers  to  the  Pancreas. — The  pancreas 
receives  its  nerve  supply  immediately  from  the  celiac  plexus,  but 
stimulation  of  the  nerves  going  to  this  plexus — namely,  the  splanch- 
nics  and  the  vagi — have  given  negative  results  in  the  hands  of  most 
observers  so  far  as  the  pancreatic  secretion  is  concerned.  Pawlow  f 
and  his  coworkers  claim  to  have  been  more  successful.  Mechanical 
stimulation  or  electrical  stimulation  of  the  vagus  or  splanchnic  gave 

*See  Glaessner,  "Zeitschrift  f.  physiol.  Chemie,"  40,  465,  1903.  Also 
Wohlgemuth,  "Biochem.  Zeitschrift,"  39,  302,  1912. 

t  For  recent  work  upon  the  pancreas  and  the  literature  see  Pawlow, 
"The  Work  of  the  Digestive  Glands,"  translation  by  Thompson,  1902;  Bay- 
liss  and  Starling,  "Journal  of  Physiology,"  30,  61,  1904;  Walter,  "Archives 
des  sciences  biologiques,"  7,  1,  1899. 


DIGESTION  AND  ABSORPTION  IN  THE  INTESTINES. 


795 


them  a  marked  flow  of  pancreatic  juice,  but  when  the  latter  form  of 
stimulus  was  used  upon  the  splanchnic,  it  was  necessary  to  cut 
the  nerve  some  days  previously  in  order  that  the  vasoconstrictor 
fibers  might  degenerate.  The  secretion  provoked  by  stimulation 
of  the  vagus  is  more  easily  obtained  when  the  stimulus  is  applied 
to  the  nerve  in  the  thorax  below  the  origin  of  the  branches  to  the 
neart.  The  secretion  obtained  upon  stimulation  of  the  nerves 
is  characterized,  as  in  the  case  of  the  gastric  glands,  by  a  long 
latent  period  of  some  minutes, — a  fact  that  is  explained,  although 
not  satisfactorily,  on  the  assumption  that  the  nerve  trunks  stimu- 


At 


A 


.JfciUi. 


.(ftiead. 


Fig.  296. — Four  curves  of  the  secretion  of  the  pancreatic  juice,  the  three  in  black, 
from  Walter,  showing  the  secretion  in  dogs  on  different  diets:  (1)  on  600  c.c.  of  milk;  (2) 
on  250  gms.  bread;  (3)  on  100  gms.  of  meat.  The  curve  hi  red,  from  Glaessner,  shows 
the  secretion  in  man  on  a  mixed  diet,  soup,  meat,  and  bread.  The  figures,  1,  2,  3  etc., 
along  the  abscissa  indicate  hours  after  the  beginning  of  the  meal.  The  figures  along  the 
ordinates  indicate  the  quantity  of  the  secretion  in  cubic  centimeters. 


lated  contain  both  secretory  and  inhibitory  fibers  and  that  the 
antagonistic  action  of  the  latter  delays  the  appearance  of  the 
secretion.  These  observations  have  been  taken  as  proof  of  the 
existence  of  secretory  nerve  fibers  to  the  pancreas,  the  fibers 
running  chiefly  in  the  vagus  nerve. 

The  Curve  of  Secretion. — The  rate  of  flow  of  the  pancreatic 
juice  with  reference  to  the  period  of  digestion  has  been  determined 
by  a  number  of  observers.  In  the  careful  experiments  reported  by 
Walter  it  is  shown  that  the  quantity  of  secretion  is  dependent  to  a 
considerable  extent  upon  the  character  of  the  food.  Thus,  the 
flow  is  more  abundant  and  reaches  its  maximum  sooner  after  a 


796  PHYSIOLOGY  OF  DIGESTION  AND  SECRETION. 

meal  of  bread  alone  than  after  a  meal  of  meat  alone.  It  seems 
possible  that  the  latter  point,  the  time  at  which  the  maximum  flow 
is  reached,  may  depend  upon  the  difference  in  rate  at  which  these 
foods  are  ejected  from  the  stomach.  Cannon  (p.  729)  .has  shown  that 
the  carbohydrate  foods  leave  the  stomach  sooner  than  the  proteins  or 
fats.  It  is  stated,  however,  that  the  composition  of  the  secretion 
varies  also  with  the  character  of  the  food,  and  indeed  shows  an 
adaptation  to  the  character  of  the  food.  The  secretion  caused  by 
protein  food  is  especially  rich  in  trypsin,  that  caused  by  fatty  food 
in  lipase,  etc.  The  mechanism  by  which  this  adaptation  is  secured 
is  not  understood.  Glaessner*  has  measured  the  rate  of  flow  in 
man,  and  his  curve  for  a  mixed  diet  is  represented  also  (in 
red)  in  Fig.  296.  These  curves  indicate  in  general  that  the  secretion 
of  pancreatic  juice  begins  very  soon  after  food  enters  the  stomach, 
and  increases  rapidly  to  a  maximum,  which  is  reached  somewhere 
between  the  second  and  fourth  hour.  According  to  Glaessner's 
case,  there  is  a  continuous  small  secretion  of  the  juice  during  fast- 
ing. The  observations  on  dogs,  on  the  contrary,  indicate  an 
entire  cessation  of  the  flow  when  the  stomach  is  empty. 

Boldirefff  has  reported  a  very  curious  activity  of  the  digestive  organs 
during  fasting.  It  seems  that  (in  dogs)  when  the  stomach  or  even  the  small 
intestine  is  empty  the  entire  gastro-intestinal  canal  exhibits  periodical  out- 
breaks of  activity,  which  occur  at  intervals  of  two  hours  and  last  for  twenty 
to  thirty  minutes.  During  this  stage  the  stomach  and  intestines  exhibit 
movements,  and  there  is  an  abundant  secretion  of  pancreatic  juice,  bile,  and 
intestinal  juice,  which  is  subsequently  absorbed.  Acids  introduced  into 
the  stomach  or  intestines  prevent  the  occurrence  of  these  periods,  and  they 
are  absent,  therefore,  as  long  as  the  stomach  contains  gastric  juice.  The 
author's  suggestion  that  the  secretions  thus  formed  furnish  active  enzymes 
which  are  absorbed  into  the  blood  and  utilized  by  the  tissues  in  destroying 
the  newly  absorbed  food  does  not  commend  itself  as  probable. 

Normal  Mechanism  of  the  Pancreatic  Secretion — Secretin. 

— Much  light  was  thrown  upon  the  mechanism  of  pancreatic  secretion 
by  the  discovery  (Dolinsky,  1895)  that  acids  brought  into  contact 
with  the  mucous  membrane  of  the  duodenum  set  up  promptly  a 
secretion  of  pancreatic  juice.  Since  this  discovery  it  has  been  be- 
lieved that  the  acid  gastric  juice  is  the  means  that  serves  to  inaugurate 
the  flow  from  the  pancreas.  As  soon  as  any  of  the  acid  contents  of 
the  stomach  pass  through  the  pylorus  this  action  begins.  Just  as  the 
chewing  and  swallowing  of  the  food  initiate  the  gastric  secretion,  so 
the  acid  of  the  latter  starts  the  pancreatic  secretion.  Assuming 
that  the  pancreatic  gland  possesses  secretory  fibers  it  was  thought  at 
first  that  the  acid  acts  reflexly  through  these  fibers — that  is,  the  acid 
in  the  duodenum  acting  upon  sensory  endings  causes  a  reflex  stimu- 
lation of  the  efferent  secretory  fibers.  It  has  been  shown,  however, 
that  the  same  effect  takes  place  after  section  of  the  vagus  and 

*  Glaessner,  loc.cit. 

t  Boldireff,  "Archives  des  sciences  biologiques, "  11,  1,   1905. 


DIGESTION  AND  ABSORPTION  IN  THE  INTESTINES.  797 

splanchnic  nerves  (Popielski),  and  Bayliss  and  Starling  *  have  called 
attention  to  another  more  probable  explanation.  These  authors  find 
that  if  the  mucous  membrane  of  the  duodenum  (or  jejunum)  is 
scraped  off  and  treated  with  acid  (0.4  per  cent.  HC1)  the  extract 
thus  made  when  injected  into  the  blood  sets  up  an  active  secretion  of 
pancreatic  juice.  They  have  shown  that  this  effect  is  due  to  a  special 
substance,  secretin,  which  is  formed  by  the  action  of  the  acid  upon 
some  substance  (prosecretin)  present  in  the  mucous  membrane. 
Secretin  is  not  an  enzyme,  since  its  activity  is  not  destroyed  by  boil- 
ing nor  by  the  action  of  alcohol.  The  experimental  evidence  at 
present  favors  the  view  that  the  normal  sequence  of  events  is  as 
follows:  The  acid  of  the  gastric  juice  upon  reaching  the  duodenum 
produces  secretin;  this  in  turn  is  absorbed  by  the  blood,  carried  to 
the  pancreas,  and  stimulates  this  organ  to  activity.  The  pan- 
creatic secretion  furnishes,  therefore,  a  second  example  of  the  group 
of  substances  designated  by  Starling  as  hormones  (p.  783).  Accord-- 
ing  to  the  evidence  at  present  in  our  possession  we  must  believe 
that  the  pancreatic  secretion,  like  the  gastric  secretion,  consists 
of  two  parts:  1,  A  nervous  secretion  caused  by  the  secretory 
fibers  in  the  vagus  and  splanchnic;  2,  a  chemical  secretion  due  to 
the  action  of  the  secretin.  These  two  secretions  are  said  to 
present  quite  different  characters.!  The  former  is  thick,  opales- 
cent, rich  in  ferments  and  proteins,  but  poor  in  alkalies.  The 
trypsin  contained  in  it  may  be  secreted  in  active  form,  and  the 
secretion  is  suspended  by  the  action  of  atropin.  Administration 
of  pilocarpin,  on  the  contrary,  excites  this  secretion.  The  chemical 
secretion,  on  the  contrary,  is  thin  and  watery,  contains  relatively 
little  ferment  or  proteins,  and  is  rich  in  alkali.  The  trpysin  in 
it  is  secreted  in  inactive  form  (see  next  paragraph),  and  the 
secretion  is  not  affected  by  the  administration  of  atropin.  The 
normal  relation  of  these  two  forms  of  secretion  in  an  ordinary 
meal  is  not  so  apparent  as  in  the  case  of  the  gastric  secretion,  but 
will  doubtless  be  made  clear  by  subsequent  work. 

Activation  of  the  Trypsin — Enterokinase. — It  was  discovered 
in  Pawlow's  laboratory  (Chepowalnikow)  that  the  pancreatic  juice 
obtained  from  a  fistula  may  have  little  or  no  digestive  action  on 
proteins,  but  if  brought  into  contact  with  the  duodenal  membrane 
or  an  extract  of  this  membrane  it  shows  at  once  powerful  pro- 
teolytic  properties.  This  discovery  has  been  confirmed  repeatedly. 
Evidently  the  proteolytic  enzyme  of  the  juice  is  secreted  in  a 
zy mogen  or  pro-enzyme  form  (trypsinogen) ,  which  is  activated  or 
converted  to  trypsin  by  something  contained  in  the  mucous  mem- 

*  Bayliss  and  Starling,  "  Journal  of  Physiology,"  28,  235,  1902. 
fSawitsch,  "  Zentralblatt  f.  d.  ges.  Physiol.  u.  Pathol.  d.  Stoffwechsels," 
10,  1,  1909. 


798  PHYSIOLOGY    OF   DIGESTION    AND    SECRETION. 

brane  of  the  small  intestine  (duodenum,  jejunum).  This  something 
Pawlow  supposed  is  an  enzyme,  and  since  its  action  is  on  another 
enzyme,  "a  ferment  of  ferments,"  he  designated  it  as  a  kinase 
or  enterokinase.  The  action  of  the  enterokinase  is  very  prompt 
and  decided  and  was  supposed  to  be  specific,  but  later  observers 
(Delezenne-Zunz)  state  that  an  inactive  pancreatic  secretion 
may  be  activated  by  a  number  of  salts,  especially  those  of  calcium 
and  magnesium.  The  physiological  value  of  this  very  interesting 
relation  is  not  clear,  but  it  seems  possible  that  it  may  serve  to 
protect  the  living  tissues  from  the  powerful  digestive  action  of 
the  trypsin.  The  other  enzymes  of  the  pancreatic  juice,  the 
diastase  and  the  lipase,  are  secreted  in  part,  at  least,  in  active 
form. 

The  Digestive  Action  of  Pancreatic  Juice. — The  digestive 
action  of  the  secretion  depends  upon  the  three  enzymes,  trypsin, 
diastase  (amylase),  and  lipase.  The  specific  effects  of  each  may 
be  considered  separately. 

Action  of  Trypsin. — The  activated  trypsinogen  causes  hydrolytic 
cleavage  of  the  protein  molecule  in  a  manner  analogous  to  that 
described  for  pepsin.  Its  action  differs  from  that  of  pepsin,  however, 
in  several  respects.  It  attacks  the  protein  in  neutral  as  well  as  in 
slightly  acid  or  markedly  alkaline  solutions.  Its  effect  upon  the 
protein  is  more  rapid  and  powerful  than  that  of  pepsin  and  the 
protein  molecule  is  broken  up  more  completely.  As  was  said  in 
describing  the  action  of  pepsin,  it  and  the  trypsin  really  act  in 
series — the  change  begun  by  the  pepsin  is  completed  by  the  tryp- 
sin. The  preliminary  action  of  the  pepsin  not  only  hastens  that  of 
the  trypsin,  but  to  some  extent  alters  it;  a  protein  submitted  first 
to  pepsin  and  then  to  trypsin  is  more  completely  broken  up  than  if 
the  trypsin  acted  alone.  The  steps  in  the  hydrolysis  of  the  protein 
molecule  by  trypsin  have  been  the  subject  of  a  very  great  amount  of 
study,  and  views  as  to  the  details  have  changed  somewhat  from 
time  to  time.  It  would  seem  that  the  trypsin,  like  the  pepsin, 
hydrolyzes  the  simple  proteins  first  to  a  proteose,  and  then  to  a  pep- 
tone stage,  but  the  latter  product  may  be  split  still  further  into  a 
variety  of  simpler  bodies,  the  number  and  character  of  which  de- 
pend on  the  amount  of  trypsin  and  the  time  that  it  acts.  After 
a  prolonged  pancreatic  digestion  no  peptone  or  peptone-like 
body  can  be  found;  in  fact,  no  substance  which  gives  a  biuret  reac- 
tion. Under  such  conditions  the  protein  molecule  is  broken  up  very 
completely  into  a  great  number  of  smaller  molecules,  many  of 
which  have  been  identified,  while  some  have  as  yet  escaped  de- 
tection so  far  as  their  chemical  structure  is  concerned.  The  actual 
products  formed  depend  on  the  length  of  time  the  trypsin  is  allowed 


DIGESTION   AND    ABSORPTION    IN    THE    INTESTINES.  799 

to  act  and  the  conditions,  favorable  or  unfavorable,  under  which  it 
acts.  The  end-products  usually  obtained  most  easily  are  tyrosin, 
leucin,  aspartic  acid,  glutaminic  acid,  tryptophan,  lysin,  arginin, 
histidin.  The  first  two  of  these  substances  have  been  known  for  a 
long  time  and  may  be  obtained  easily  in  crystalline  form  from 
pancreatic  digestions.  If  the  trypsin  is  allowed  to  exert  its  com- 
plete action  upon  the  protein,  the  end-products  are  closely  similar 
to  those  obtained  by  boiling  protein  with  acids.  The  hydrolysis 
caused  by  the  acids  and  by  the  trypsin  seems  to  be  nearly  identical, 
although  that  caused  by  the  acids  is  probably  more  complete  and 
perhaps  is  attended  by  secondary  reactions.  The  numerous  prod- 
ucts obtained  by  this  complete  hydrolysis  consist  chiefly  of  amino- 
acids — that  is,  organic  acids  containing  one  or  more  amino-groups 
(NH2)  in  direct  union  with  carbon.  Most  of  them  are  monamino- 
acids,  that  is,  contain  one  NH2  group,  and  this  group  is  united  with 
the  carbon  occupying  the  alpha  position.  The  nitrogen  of  the 
protein  molecule  appears  in  the  split  products  chiefly  as  amino- 
acids,  but  in  small  part  as  ammonia. 

A  list  of  the  known  amino-acids  obtained  from  proteolytic 
cleavage  of  the  protein  molecule  is  appended.  For  a  more  com- 
plete description  of  their  properties  and  chemical  relationships 
reference  must  be  made  to  text-books  on  physiological  chemistry. 
With  regard  to  the  nomenclature  used,  it  will  be  borne  in  mind 
that  the  various  carbon  atoms  in  the  straight  chain  of  the  fatty 
acids  are  designated  by  Greek  letters  that  indicate  their  position 
in  relation  to  the  carboxyl  (COOH)  group,  as  may  be  illustrated 
by  the  formula  for  caproic  acid: 

CH3    CH2    CH2    CH2    CH2    COOH 

e  5  70  a 

I.     AMINO-ACIDS  OF  THE  FATTY  ACID  (ALIPHATIC)  SERIES. 

1.  Glycocoll  or  glycin  (amino-acetic  acid): 

CH2NH2COOH. 

2.  Alanin  (a-aminopropionic  acid) : 

CH3CHNH2COOH. 

3.  Serin  (a-amino-/8-oxypropionic  acid) : 

CH2OHCHNH2COOH. 

4.  Cystein  (a-amino-/8-thiopropionic  acid) : 

CH2SHCHNH2COOH. 

5.  Valin  (a-amino-isopropionic  acid) : 

CH3X 

>CHCHNH2COOH. 
CH/ 


800  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

6.  Leucin  (a-amino-isobutylpropionic  acid) : 
CH3X 

>CHCH2CHNH2COOH. 
CH3/ 

Two  other  isomeric  forms  of  this  compound  have  been  obtained  from  the 
split  products,  namely: 

Isoleucin  (methyl-ethyl  a-aminopropionic  acid) : 


\CHCHNH2COOH. 


C2H6 

Normal  leucin  —  norleucin  (a-aminocaproic  acid)  : 
CH3CH2CH2CH2CHNH2COOH. 

7.  Aspartic  acid  (aminosuccinic  acid)  : 

COOHCHNH2CH2COOH. 

8.  Glutaminic  acid: 

COOHCHNH2CH2CH2COOH. 

9.  Lysin  (a-  e-diaminocaproic  acid)  : 

CH2NH2CH2CH2CH2CHNH2COOH. 

10.  Arginin  (guanidin  a-aminovalerianic  acid): 

/NH2 
C=NH 

\NHCH2CH2CH2CHNH2COOH. 

II.    AMINO-ACIDS  CONTAINING  A  BENZENE  (HOMOCYCLIC)  OR  A  HETERO- 
CYCLIC  NUCLEUS. 

These  compounds  may  be  regarded  as  a-aminopropionic  acids  in  which  a 
hydrogen  attached  to  the  /3-carbon  atom  is  substituted  by  a  benzene,  an  indol, 
or  an  imidazol  group. 

1.  Phenylalanin  (a-amino-|8-phenylpropionic  acid)  : 

C6H5CH2CHNH2COOH,  or 
H 


HC 


\ 

CH 


C  . 


CH2CHNH2COOH. 

2.  Tyrosin  (a-amino-/8-para-oxyphenylpropionic  acid)  : 

C6H4OHCH2CHNH2COOH,  or 
OH 

^c\ 

HC        CH 

HC        CH 

%  / 
C  .  CH2CHNH2COOH. 


DIGESTION   AND   ABSORPTION   IN   THE    INTESTINES.  801 

3.  Tryptophan  (a-amino-/8-indolpropionic  acid): 

C8H6NCH2CHNH2COOH,  or 
CH 


i 


.  CH2CHNH2COOH. 


H 


4.  Histidin  (a-amino-/3-imidazolpropionic  acid): 

C3H2N2CH2CHNH2COOH,  or 
HC— NH 


N 
H2CHNH2COOH. 


III.     THE  PYRROL  SERIES. 
1.  Prolin  (a-pyrollidin  carboxylic  acid)  : 
H2C  -  CH2 


H2C        C 


HCOOH 


2.  Oxyprolin  (oxypyrollidin  carboxylic  acid)  : 
HOHC  -  CH2 

H2C        CHCOOH. 


The  Significance  of  Tryptic  Digestion.  —  It  was  formerly 
supposed  that  the  object  of  peptic  and  tryptic  digestion  is  to  con- 
vert the  insoluble  and  non-dialyzable  proteins  into  the  simpler, 
more  soluble,  and  more  diffusible  peptones  and  proteoses.  In  this 
way  absorption  of  protein  material  was  explained.  This  view, 
however,  is  not  sufficient.  On  the  one  hand,  it  has  not  been  pos- 
sible to  prove  conclusively  that  peptones  or  proteoses  are  found  in 
the  blood;  on  the  other  hand,  a  better  knowledge  of  the  processes  of 
tryptic  or  of  tryptic-ereptic  digestion  has  shown  that  the  hydrolysis 
does  not  stop  at  the  peptone  stage;  the  protein  molecule  is  hydro- 
lyzed  still  further  with  the  production  of  simpler  molecules.  At 
present  different  views  exist  as  to  the  extent  of  this  latter  process. 
Some  believe  that  the  protein  molecule  is  entirely  broken  down  into 
its  so-called  building-stones,  that  is,  the  various  amino-acids,  de- 
scribed on  the  preceding  page.  This  view  is  supported  by  the  dis- 
covery of  the  existence  of  the  enzyme  erepsin  (see  below)  in  the 
51 


802  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

intestinal  mucosa.  The  action  of  this  latter  enzyme  is  exerted 
especially  upon  the  albumoses  and  peptones,  breaking  them  down 
into  the  amino-acids,  so  that  apparently  whatever  peptone  or 
albumose  may  escape  the  final  action  of  the  trypsin  before  absorp- 
tion is  likely  to  be  acted  upon  by  the  erepsin  before  reaching  the 
blood.*  Another  possible  view  is  that  suggested  by  Abderhalden.  f 
According  to  this  author,  the  hydrolysis  of  the  protein  by  pepsin, 
trypsin,  and  erepsin  is  not  necessarily  complete.  Some  amino- 
bodies,  such  as  tyrosin,  leucin,  arginin,  etc.,  are  split  off  from  the 
protein  molecule,  but  there  may  remain  behind  what  one  may 
call  a  nucleus  of  the  original  molecule,  which  serves  as  the  starting- 
point  for  a  synthesis.  This  nucleus  is  a  substance  or  a  number  of 
substances  intermediate  between  the  peptone  and  the  simpler 
end-products,  and  is  spoken  of  as  a  peptid  or  polypeptid  (see 
Appendix) .  It  has  been  shown  that  in  tryptic  digestion  such  sub- 
stances are  formed — that  is,  substances  which  are  not  peptones, 
since  they  no  longer  give  the  biuret  reaction,  but  which  have  a 
certain  complexity  of  structure,  since  upon  hydrolysis  with  acids 
they  split  into  a  number  of  amino-acids.  But  bearing  in  mind 
the  fact  that  the  action  of  the  trypsin  is  normally  combined  with 
or  is  supplemented  by  that  of  the  erepsin,  it  seems  probable  that  in 
digestion  in  the  body  the  protein  molecule  is  broken  down  com- 
pletely to  its  building-stones.  The  value  of  this  complete  splitting 
of  the  protein  of  the  food  lies  in  the  possibility  that  thereby  the 
body  is  able  to  construct  its  own  peculiar  type  of  protein.  Many 
different  kinds  of  proteins  are  taken  as  food,  and  many  of  them  if 
introduced  directly  into  the  blood  act  as  foreign  material  incapable 
of  nourishing  the  tissues.  If  these  proteins  are  broken  down  more 
or  less  completely  during  digestion,  the  tissue  cells  may  reconstruct 
from  the  pieces  or  building-stones  a  form  of  protein  adaptable  to 
their  needs,  and  more  or  less  characteristic  for  that  particular 
organism.  Just  as  the  letters  of  the  alphabet  may  be  combined 
in  different  ways  to  make  different  words,  so  the  various  amino- 
acids  may  be  combined  to  make  proteins  of  many  different  kinds. 
Action  of  the  Diastatic  Enzyme  (Amylase)  of  the  Pancre- 
atic Secretion. — This  enzyme  is  found  in  the  secretion  of  the 
pancreas  or  it  may  be  extracted  from  the  gland.  Its  action 
upon  starchy  foods  is  similar  to  or  identical  with  that  of  ptyalin. 
It  causes  an  hydrolysis  of  the  starch  with  the  production  finally  of 
maltose  and  achroodextrin.  Before  absorption  these  substances  are 
further  acted  upon  by  the  maltase  of  the  intestinal  secretion  and 

"Vernon  ("Journal  of  Physiology,"  30,  330,  1904)  believes  that  the 
pancreatic  secretion  contains  two  proteolytic  enzymes — trypsin  proper, 
which  converts  the  proteins  to  peptones,  and  pancreatic  erepsin,  which  breaks 
up  the  peptones  into  the  simpler  end-products,  the  amino-bodies. 

t  Abderhalden,  loc.  cit. 


DIGESTION    AND    ABSORPTION    IN    THE    INTESTINES.  803 

Converted  to  dextrose.  The  starchy  food  that  escapes  digestion  in 
the  mouth  and  stomach  becomes  mixed  with  this  enzyme  in  the 
duodenum,  and  from  that  time  until  it  reaches  the  end  of  the  large 
intestine  conditions  are  favorable  for  its  conversion  to  maltose. 
Most  of  this  digestion  is  probably  completed,  under  normal  con- 
ditions, before  the  contents  of  the  intestinal  canal  reach  the  ileo- 
cecal  valve. 

Action  of  the  Lipolytic  Enzyme  (Lipase,  Steapsin). — The 
importance  of  the  pancreatic  secretion  in  the  digestion  of  fats  was 
first  clearly  stated  by  Bernard  (1849).  We  know  now  that  this  secre- 
tion contains  an  active  enzyme  capable  of  hydrolyzing  or  saponifying 
the  neutral  fats.  These  latter  bodies  are  chemically  esters  of  the 
trihydric  alcohol  glycerin.  When  hydrolyzed  they  break  up  into 
glycerin  and  the  constituent  fatty  acid.  The  action  of  lipase  may 
be  represented,  therefore,  by  the  following  reaction,  in  the  case  of 
palmitin: 

CyH.CCJ5HMCX)0),  +  3H20  -  C,H5(OH),  +  3(C,5H31COOH) 

Palmitin.  Glycerin.  Palmitic  acid. 

When  lipase  from  any  source  is  added  to  neutral  oils  its  splitting 
action  is  readily  recognized  by  the  development  of  an  acid  reaction 
due  to  the  formation  of  the  fatty  acid.  If  a  bit  of  fresh  pancreas 
is  added  to  butter,  for  example,  and  the  mixture  is  kept  at  the  body 
temperature  the  hydrolysis  of  the  fats  is  soon  made  evident  by  the 
rancid  odor  due  to  the  butyric  acid  produced.  When  pancreatic 
juice  is  mixed  with  oils  or  liquid  fats  two  phenomena  may  be 
noticed :  first,  the  splitting  of  the  fat  already  referred  to,  and,  second, 
the  emulsification  of  the  fat.  The  latter  process  is  very  striking. 
An  oil  is  emulsified  when  it  is  broken  up  into  minute  globules  that  do 
not  coalesce.  Artificial  emulsions  may  be  made  by  vigorous  and 
prolonged  shaking  of  the  oil  in  a  viscous  solution  of  soap,  mucilage, 
etc.  Milk  may  be  regarded  as  a  natural  emulsion  that  separates 
slowly  on  standing,  as  the  fat  rises  to  the  top  to  form  the  cream. 
When  a  little  pancreatic  juice  is  added  to  oil  at  the  body  temperature 
the  mixture,  after  standing  for  some  time,  will  emulsify  reaclily  with 
very  little  shaking  or  even  spontaneously.  It  is  now  known*  that 
the  emulsification  is  due  to  the  formation  of  soaps.  The  lipase  splits 
some  of  the  fats,  and  the  fatty  acid  liberated  combines  with  the 
alkaline  salts  present  to  form  soaps.  The  emulsification  produced 
under  these  conditions  is  very  fine  and  quite  permanent,  and  it  was 
formerly  believed  that  the  formation  of  this  emulsion  is  the  main 
function  of  the  pancreatic  juice  so  far  as  fats  are  concerned.  It  was 
thought  that  in  the  form  of  fine  droplets  the  fat  may  be  taken  up 
directly  by  the  epithelial  cells  of  the  villi,  and  this  view  was  supported 

*  See  Ratchford,  "Journal  of  Physiology,"  12,  27,  1891. 


804  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

by  the  histological  fact  that  during  the  digestion  of  fats  the  epithelial 
cells  may  be  shown  to  contain  fine  oil  drops  in  their  interior.  The 
tendency  of  recent  work,  however,  has  been  to  indicate  that  the  fats 
are  completely  split  into  fatty  acids  and  glycerin  before  absorption, 
and  that  the  emulsification  may  be  regarded,  from  a  physiological 
standpoint,  as  a  mechanical  preparation  for  the  action  of  the  lipase 
rather  than  as  a  direct  preparation  for  the  act  of  absorption.  The 
two  products  of  the  action  of  the  lipase,  the  glycerin  and  the  fatty 
acid,  are  absorbed  by  the  epithelium  and  again  combined  to  form 
neutral  fat.  It  is  very  probable,  moreover,  that  during  this 
synthesis  the  fatty  acids  are  combined  with  the  glycerine  in  such 
proportions  as  to  make  for  the  most  part  the  fat  characteristic 
of  the  animal,  fat  of  a  high  melting-point  in  the  case  of  the 
sheep,  for  example,  and  of  a  lower  melting-point  for  the  dog. 
In  connection  with  this  fact  of  a  synthesis  of  the  split  products 
to  form  neutral  fat,  the  discovery  by  Kastle  and  Loevenhart 
(see  p.  750)  that  the  action  of  lipase  is  reversible  assumes  much 
significance.  It  seems  quite  possible  that  the  same  enzyme  may 
cause  both  the  splitting  of  the  fat  and  the  synthesis  of  the  split 
products,  not  only  in  the  intestine  during  absorption,  but  in  the 
various  tissues  during  the  metabolism  or  the  storage  of  fat.  Lipase 
is  found  in  the  blood  and  in  many  tissues, — muscle,  liver,  mammary 
gland,*  etc. — and  during  its  nutritive  history  in  the  body  the  fat 
may  be  split  and  synthesized  a  number  of  times.  In  this  connection 
it  is  interesting  to  note  that  the  process  of  splitting  does  not  involve 
much  work.  Very  little  heat  is  liberated  in  the  process,  and  a  cor- 
respondingly small  amount  of  energy  is  needed  for  the  synthesis,  f 

The  lipase  as  formed  in  the  pancreas  is  easily  destroyed,  especially 
by  acids.  For  this  reason  probably  it  is  not  found  usually  in  simple 
extracts  of  the  gland  made  by  laboratory  methods.  It  should  be 
added,  also,  that  the  action  of  this  enzyme  is  aided  very  materially 
by  the  presence  of  bile.  This  latter  secretion  contains  no  lipase 
itself,  but  mixtures  of  bile  and  pancreatic  juice  split  the  neutral 
fats  much  more  rapidly  than  the  pancreatic  juice  alone.  This 
effect  is  now  explained  on  the  hypothesis  that  the  bile-acids  or 
the  bile-acids  and  the  lecithin  either  activate  a  portion  of  the 
lipase  which  is  in  the  state  of  a  proferment  or  play  the  part  of  a 
coferment  (page  755). 

The  Intestinal  Secretion  (Succus  Entericus)  .—The  small 
intestine  is  lined  with  tubular  glands,  the  crypts  of  Lieberkiihn, 
which  in  parts  of  the  intestine  at  least  give  rise  to  a  liquid  secretion, 
the  so-called  intestinal  juice.  To  obtain  this  secretion  recourse  has 
been  had  to  the  operation  known  as  the  Thiry-Vella  fistula.  In  this 

*  See  Loevenhart,  " American  Journal  of  Physiology,"  6,  331,  1902. 
t  Consult  Herzog,  "Zeitschrift  f.  physiol.  Chemie,"  37,  383,  1903. 


DIGESTION   AND    ABSORPTION    IN    THE    INTESTINES.  805 

operation  a  small  portion  of  the  intestine  is  isolated  by  cutting 
through  the  intestinal  wall  at  two  points  a  certain  distance  apart. 
The  continuity  of  the  canal  is  re-established  by  appropriate 
suture,  while  the  piece  cut  out,  with  its  blood  and  nerve-supply 
intact,  is  given  an  opening  to  the  exterior  at  one  or  both  ends  by 
suturing  to  the  abdominal  wall.  In  this  way  a  small  pouch  or  loop 
of  the  intestine  is  separated  from  the  rest  of  the  alimentary  canal 
and  is  so  arranged  that  its  secretion  can  be  obtained  through  the 
fistulous  openings,  or  material  of  any  kind  can  be  introduced 
into  the  loop  and  be  removed  after  a  given  time  to  determine  what 
absorption  has  taken  place.  The  secretion  from  these  loops  is 
usually  said  to  be  small  in  quantity,  especially  in  the  jejunum. 
Pregl  estimates  that  as  much  as  three  liters  may  be  formed  in  the 
whole  of  the  small  intestine  in  the  course  of  a  day,  but  this  esti- 
mate does  not  rest  upon  very  satisfactory  data.  The  liquid  gives 
an  alkaline  reaction,  owing  to  the  presence  of  sodium  carbonate. 
Experiments  have  shown  that  this  liquid  has  little  or  no  digestive 
action  except  upon  the  starches,  and  it  may  perhaps  be  doubted 
whether  it  is  a  true  digestive  secretion.  Extracts  of  the  walls  of 
the  small  intestine  or  the  juice  squeezed  from  these  walls  have  been 
found,  on  the  contrary,  to  contain  four  or  five  different  enzymes 
and  to  exert  a  most  important  influence  upon  intestinal  digestion. 
These  enzymes  belong  probably  to  the  group  of  endo-enzymes,  and 
are  not  actually  secreted  into  the  lumen  of  the  intestines.  While 
they  are  not,  strictly  speaking,  constituents  of  the  intestinal  juice, 
nevertheless  it  is  their  action  on  the  food  which  forms  the  charac- 
teristic contribution  to  the  process  of  digestion  made  by  the  glands 
of  the  intestinal  wall.  These  enzymes  and  their  actions  are  as 
follows : 

1.  Enterokinase  (see  p.  797),  an  enzyme  which  in  some  way  acti- 
vates the  proteolytic  enzyme  of  the  pancreatic  juice,  by  converting 
the  trypsinogen  to  trypsin. 

2.  Erepsin.     This  enzyme,   discovered  by  Cohnheim,*  acts 
especially  upon  the  proteoses  and  peptones,  causing  further  hydro- 
lysis.    Its  splitting  action  upon  the  peptones  is  supposed  to  be 
complete,  and  the  natural  suggestion  regarding  this  enzyme  is  that 
it  supplements  the  work  begun  by  the  trypsin  and  pepsin.     Erepsin 
occurs  not  only  in  the  intestinal  mucosa,  but  also,  it  is  claimed,  in 
the  liver,  kidney,  and  pancreas,  and  perhaps  in  other  tissues.     Its 
characteristic  is  that  it  is  adapted  especially  to  hydrolyze  the  pro- 
teoses and  peptones.      On  the  theory  that  proteins  during  digestion 
are  broken  down  completely  to  their  constituent  amino-acids,  the 
importance  of  this  enzyme  in  the  normal  digestion  of  proteins  has 

*  Cohnheim,  "Zeitschrift  f.  physiol.  Chemie,"  33,  451,  1901;  also  35,  134, 
et  seq.;  Kobzarenko,  "Biochemische  Zeitschrift,"  66,  344,  1914. 


806  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

gained  increased  recognition  in  reoent  years.  The  digestion  of  the 
protein  begun  by  the  pepsin  or  by  the  trypsin  is  carried  to  comple- 
tion by  the  action  of  the  erepsin. 

•  3.  Inverting  enzymes  capable  of  converting  the  disaccharids  into 
the  monosaccharids.  These  enzymes  are  three  in  number :  maltase, 
which  acts  upon  maltose  (and  dextrin);  invertase  or  invertiri, 
which  acts  upon  cane-sugar;  and  lactase,  which  acts  upon  lactose. 
The  maltase  acts  upon  the  products  formed  in  the  digestion  of 
starches,  the  maltose  and  dextrin,  converting  them  to  dextrose 
according  to  the  general  formula: 

Ci2H22Oii  +  H2O   =  C6H12O6  +  C6H12O6 

Maltose.  Dextrose.          Dextrose. 

In  the  same  way  invertase  converts  cane-sugar  to  dextrose  and 
levulose,  and  lactase  changes  milk-sugar  to  dextrose  and  galac- 
tose.  This  inverting  action  is  necessary  to  prepare  the  carbohy- 
drate food  for  nutritive  purposes.  Double  sugars  cannot  be  used 
by  the  tissues  and  would  escape  in  the  urine,  but  in  the  form  of 
dextrose  or  dextrose  and  levulose  they  are  readily  used  by  the  tis- 
sues in  their  normal  metabolic  processes. 

4.  Nuclease.     An  enzyme  to  which  this  name  may  be  given  is 
said  to  occur  in  the  small  intestine.     It  acts  upon  the  nucleic-acid 
component  of  nucleoproteins  splitting  it  with  the  formation  of  the 
corresponding  purin  and  pyrimidin  nucleotides  (see  p.  858). 

5.  Secretin.     As  explained  above,  this  hormone  plays  an  im- 
portant r61e  in  the  control  of  the  secretion  of  the  pancreas.     It  is 
not  an  enzyme,  but  a  more  stable  and  definite  chemical  substance 
which  is  secreted  or  formed  in  the  intestinal  mucosa  in  a  preliminary 
form,  prosecretin,  and  under  the  influence  of  acids  is  changed  to 
secretin.     In  this  latter  form  it  is  absorbed,  carried  to  the  pancreas, 
and  causes  a  flow  of  pancreatic  secretion. 

Absorption  in  the  Small  Intestine. — Absorption  takes  place 
very  readily  in  the  small  intestine.  The  general  correctness  of  this 
statement  may  be  shown  by  the  use  of  isolated  loops  of  the  intestine. 
Salt  solutions  of  varying  strengths  or  even  blood-serum  nearly 
identical  in  composition  with  the  animals'  own  blood  may  be  ab- 
sorbed completely  from  these  loops.  Examination  of  the  contents 
of  the  intestine  in  the  duodenum  and  at  the  ileocecal  valve  shows 
that  the  products  formed  in  digestion  have  largely  disappeared  in 
traversing  this  distance.  All  the  information  that  we  possess  in- 
dicates, in  fact,  that  the  mucous  membrane  of  the  small  intestine 
absorbs  readily,  and  it  is  one  of  the  problems  of  this  part  of  physiology 
to  explain  the  means  by  which  this  absorption  is  effected.  Anatomi- 
cally two  paths  are  open  to  the  products  absorbed.  They  may  enter 
the  blood  directly  by  passing  into  the  capillaries  of  the  villi,  or  they 


DIGESTION    AND    ABSORPTION    IN    THE    INTESTINES.  807 

may  enter  the  lacteals  of  the  villi,  pass  into  the  lymph  circulation, 
and  through  the  thoracic  duct  of  the  lymphatic  system  eventually 
reach  the  blood  vascular  system.  The  older  physiologists  assumed 
that  absorption  takes  place  exclusively  through  the  central  lacteals 
of  the  villi,  and  hence  these  vessels  were  described  as  the  absorb- 
ents. We  now  know  that  the  digested  and  resynthesized  fats  are 
absorbed  by  way  of  the  lacteals,  but  that  the  other  products  of  di- 
gestion are  absorbed  mainly  through  the  blood-vessels,  and  therefore 
enter  the  portal  system  and  pass  through  the  liver  before  reaching 
the  general  circulation.  According  to  observations  made  upon  a  pa- 
tient with  a  fistula  at  the  end  of  the  small  intestine,*  food  begins  to 
pass  into  the  large  intestine  in  from  two  to  five  and  a  quarter  hours 
after  eating,  and  it  requires  nine  or  more  hours  before  the  last  of  a 
meal  has  passed  the  ileocecal  valve ;  this  estimate  includes,  of  course, 
the  time  in  the  stomach.  During  this  passage  absorption  of  the 
digested  products  takes  place  nearly  completely.  In  the  fistula  case 
referred  to  above  it  was  found  that  85  per  cent,  of  the  protein  had 
disappeared,  and  similar  facts  are  known  regarding  the  other  food- 
stuffs. The  problems  that  have  excited  the  greatest  interest  have 
been,  first,  the  exact  form  in  which  the  digested  products  are  ab- 
sorbed, and,  second,  the  means  by  which  this  absorption  is  effected. 
With  regard  to  the  last  question,  much  work  has  been  done  to 
ascertain  whether  the  known  physical  laws  of  diffusion,  osmosis, 
and  imbibition  are  sufficient  to  account  for  the  movements  of  the 
absorbed  substances  or  whether  it  is  necessary  to  refer  them  in 
part  to  some  unknown  activities  of  the  living  epithelial  cells.  It 
would  seem  that  diffusion  and  osmosis  occur  in  the  intestines. 
Concentrated  solutions  of  neutral  salts, — sodium  chlorid,  for  instance, 
— if  introduced  into  a  Thiry-Vella  loop,  cause  a  flow  of  water  into 
the  lumen  in  accordance  with  their  high  osmotic  pressure,  and,  on 
the  other  hand,  some  of  the  sodium  chlorid  diffuses  into  the  blood 
in  accordance  with  the  laws  of  diffusion.  It  seems  equally  clear, 
however,  that  absorption  as  it  actually  takes  place  is  not  governed 
simply  by  the  differences  in  concentration  between  the  contents 
of  the  intestine  and  the  blood  or  lymph,  but  depends  largely 
upon  the  properties  of  the  separating  wall  of  living  epithelial  cells. 
Thus,  the  animal's  own  serum,  t  possessing  presumably  the  same 
concentration  and  osmotic  pressure  as  the  animal's  blood,  is  ab- 
sorbed completely  from  an  isolated  intestinal  loop.  So  also  it  has 
been  shown  that  in  the  absorption  of  salts  from  the  intestine  f the 

*  Macfayden,  Nencki,  and  Sieber, "  Archiv  f.  experiment.  Pathol.  u.  Phar- 
macol.,"  28,  311,  1891 

fHeidenhain,  "Archiv  f.  die  gesammte  Physiologic,"  56,  579,  1894. 

t  Wallace  and  Cushny,  "Archiv  f.  die  gesammte  Physiologic,"  77,  202, 
1899. 


808  PHYSIOLOGY    OF   DIGESTION   AND    SECRETION. 

rapidity  of  absorption  stands  in  no  direct  relation  to  the  diffusion 
velocity.  The  energy  that  effects  the  absorption  is  furnished,  there- 
fore, by  the  wall  of  the  intestine,  presumably  by  the  epithelial  cells. 
That  this  particular  form  of  energy  is  connected  with  the  living 
structure  is  shown  by  the  fact  that  when  the  walls  are  injured  by 
the  action  of  sodium  fluorid,  potassium  arsenate,  etc.,  their  absorp- 
tive power  is  diminished  and  absorption  then  follows  the  laws  of 
diffusion  and  osmosis.* 

Absorption  of  the  Carbohydrates. — Our  carbohydrate  food  is 
absorbed,  for  the  most  part,  as  simple  sugars, — monosaccharids. 
As  has  been  said,  there  is  reason  to  believe  that  but  little  sugar  is 
absorbed  in  the  stomach.  Cane-sugar  and  milk-sugar  are  inverted 
in  the  small  intestine  by  invertase  and  lactase,  the  first  being  con- 
verted to  dextrose  and  levulose,  the  second  to  dextrose  and  galactose. 
If,  however,  these  substances  are  fed  in  excess  they  are  absorbed  in 
part  without  conversion  to  simple  sugar,  and  in  that  case  may  be 
eliminated  in  the  urine.  The  bulk  of  our  carbohydrate  food  is  taken, 
however,  in  the  form  of  starch,  and  the  conditions  for  absorption  in 
this  case  are  more  favorable.  The  time  required  for  the  digestion  of 
the  starch  to  maltose  and  dextrin,  and  the  subsequent  inversion  of 
these  substances  to  dextrose,  insures  a  slower  and  more  complete 
absorption.  Five  hundred  grams  or  more  of  starch  may  be  digested 
and  absorbed  in  the  course  of  the  day  and  it  all  reaches  the  blood  in 
the  form  of  dextrose.  This  dextrose  enters  the  portal  vein  and  is 
distributed  first  to  the  liver.  In  this  organ  the  excess  of  sugar  is 
withdrawn  from  the  blood  and  stored  as  glycogen,  so  that  the  amount 
of  sugar  in  the  general  circulation  is  thereby  kept  quite  constant, — 
about  0.15  per  cent.  When  a  large  amount  of  carbohydrate  food  is 
eaten,  however,  it  is  possible  that  the  liver  may  not  be  able  to  remove 
the  excess  completely.  In  that  case  the  amount  of  sugar  in  the  gen- 
eral circulation  may  be  increased  above  normal,  giving  a  condition 
of  hyperglycemia,  and  the  excess  may  be  excreted  in  the  urine, 
thus  bringing  about  the  condition  known  as  "alimentary  glyco- 
suria."  The  amount  of  any  carbohydrate  that  can  be  eaten' 
without  producing  alimentary  glycosuria  is  designated  by  Hof- 
meister  f  as  the  assimilation  limit  of  that  carbohydrate  or,  to  use 
another  terminology,  it  establishes  the  degree  of  tolerance  of  the 
animal  for  the  particular  carbohydrate  employed.  If  taken 
beyond  this  limit  there  is  a  physiological  excess,  and  some  sugar 
is  lost  in  the  urine.  The  assimilation  limit  varies  with  a  great 
many  conditions;  but,  so  far  as  the  different  forms  of  carbo- 
hydrates are  concerned,  it  is  lowest  for  the  milk-sugar  and  high- 

*  Cohnheim,  "Zeitschrift  f.  Biologie,"  37,  443,  1899. 
t  Hofmeister,  "Archiv.  f.  exper.  Pathol.  u.  Pharmakol.,"  25,  240,  1889, 
and  26,  355,  1890. 


DIGESTION    AND    ABSORPTION    IN    THE    INTESTINES.  809 

est  for  starch.  That  starch  may  be  eaten  in  larger  amounts 
than  sugar  without  raising  the  percentage  of  sugar  in  the  sys- 
temic blood  above  the  normal  level  is  in  accord  with  what  we 
know  of  the  digestion  of  the  two  forms  of  carbohydrates.  Dex- 
trose requires  no  digestion,  it  is  absorbed  as  such,  while  cane- 
sugar  needs  only  to  be  inverted.  Starch,  on  the  contrary,  requires 
the  action  of  ptyalin  or  amylase  and  subsequent  inversion  by 
maltase.  Its  absorption  will,  therefore,  be  much  slower  than  that 
of  the  sugars.  In  fact,  it  probably  goes  on  for  the  period  of  four 
or  five  hours,  during  which  an  ordinary  meal  is  making  its  progress 
from  pylorus  to  ileocecal  valve.  During  this  period  the  entire 
quantity  of  blood  in  the  body  is  passed  through  the  mesenteric 
arteries  over  and  over  again,  and  it  is  probable  that  even  in  the 
portal  vein  the  quantity  of  sugar  at  any  one  moment  rises  but 
little  above  the  normal  level,  and  this  small  excess  is  held  back 
by  the  liver  cells,  so  that  the  systemic  circulation  is  protected 
from  becoming  hyperglycemic. 

So  far  as  the  carbohydrates  escape  absorption  as  sugar  they  are 
liable  to  undergo  acid  fermentation  from  the  bacteria  always  present 
in  the  intestine.  As  the  result  of  this  fermentation  there  may  be 
produced  acetic  acid,  lactic  acid,  butyric  acid,  succinic  acid,  carbon 
dioxid,  alcohol,  hydrogen,  etc.  This  fermentation  probably  occurs 
to  some  extent  in  the  small  intestines  under  normal  conditions. 
Macfadyen,*  in  the  case  already  referred  to,  found  that  the  contents 
of  the  intestine  at  the  ileocecal  valve  contained  acid  equivalent  to 
that  of  a  0.1  per  cent,  solution  of  acetic  acid.  Under  less  normal 
conditions,  such  as  excess  of  sugars  in  the  diet  or -deficient  absorp- 
tion, the  large  production  of  acids  may  lead  to  irritation  of  the  intes- 
tines,— diarrhea,  etc. 

Absorption  of  Fats. — Numerous  theories  have  been  held  in 
regard  to  the  mode  of  absorption  of  fats.  It  has  been  supposed  that 
the  emulsified  (neutral)  fat  is  ingested  directly  by  the  epithelial  cells, 
that  the  fat  droplets  enter  between  the  epithelial  cells  in  the  so-called 
cement  substance,  that  the  fat  droplets  are  ingested  by  leucocytes 
that  lie  between  the  epithelial  cells,  or  lastly  that  the  fat  is  first  split 
into  fatty  acid  and  glycerin  and  is  absorbed  by  the  epithelial  cells  in 
these  forms.  The  tendency  of  recent  work  is  altogether  in  favor  of 
this  last  view,  and  we  may  adopt  it  as  expressing  the  theory  gener- 
ally accepted  at  present.  During  digestion  the  epithelial  cells  con- 
tain fat  droplets  without  doubt,  but  it  seems  probable  that  these 
droplets  are  formed  in  situ  by  a  synthesis  of  the  absorbed  glycerin 
and  fatty  acids.  The  border  of  the  cell  is  said  to  be  free  from 
fat  globules, — a  fact  which  would  indicate  that  the  neutral  fat 

*  Macfadyen,  Nencki,  and  Sieber,  Zoc.  cit. 


810  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

is  not  mechanically  digested  as  oil  drops.  But,  granting  that 
the  fat  is  absorbed  in  solution,  as  fatty  "acids  and  glycerin,  the 
mechanism  of  absorption  remains  unexplained.  It  is  known 
that  the  bile  as  well  as  the  pancreatic  juice  plays  an  important 
part  in  the  process.  The  pancreatic  juice  furnishes  the  lipase,  the  bile 
furnishes  the  bile  salts  (glycocholate  and  taurocholate  of  sodium) 
which  aid  the  lipase  in  splitting  the  neutral  fat,  and  moreover  aid 
greatly  the  absorption  of  the  split  fats.  This  latter  function  is  due 
probably  to  the  fact  that  the  bile  (bile  salts)  dissolves  the  fatty  acids 
readily*  and  thus  brings  them  into  contact,  in  soluble  form,  with  the 
epithelial  cells.  When  the  bile  is  drained  off  from  the  intestine 
by  a  fistula  of  the  gall-bladder  or  duct,  a  large  proportion  of 
the  fatty  foods  escapes  absorption  and  appears  in  the  feces.  Direct 
observation  shows  that  the  fat  after  passing  the  epithelial  lin- 
ing and  entering  the  stroma  of  the  villus  is  taken  up  by  the 
lymphatic  vessels,  the  so-called  lacteals.  This  fact  is  beautifully 
demonstrated  by  the  mere  appearance  of  the  lymphatics  of 
the  mesentery  after  a  meal  containing  fats.  These  vessels  are 
injected  with  milky  chyle  during  the  period  of  absorption  so  that 
their  entire  course  is  revealed.  The  chyle  on  microscopical  exami- 
nation is  found  to  contain  fat  in  the  form  of  an  extremely  fine 
emulsion.  In  this  form  it  is  carried  to  the  thoracic  duct  and  thence 
to  the  venous  circulation.  For  hours  after  a  meal  the  blood  contains 
this  chyle  fat.t  If  a  specimen  of  blood  is  taken  during  this  time  and 
centrifugalized  in  the  usual  way,  the  chyle  fat  may  be  collected  at 
the  top  in  the  form  of  a  cream.  It  is  an  easy  matter  to  insert  a 
cannula  into  the  thoracic  duct  at  the  point  at  which  it  opens  into  the 
subclavian  and  jugular  veins  and  thus  collect  the  entire  amount  of  fat 
absorbed  from  the  intestines  by  way  of  the  lacteals.  Experiments 
of  this  kind  show  that,  after  deducting  the  amount  of  fat  that  escapes 
absorption  and  is  lost  in  the  feces,  the  amount  that  may  be  recovered 
from  the  thoracic  duct  is  less  than  that  taken  in  the  food.  It  seems 
probable,  therefore,  that  some  of  the  fat  is  absorbed  directly  by  the 
blood-vessels  of  the  villi.  The  portion  thus  absorbed  enters  the 
portal  vein  and  passes  through  the  liver  before  reaching  the  general 
circulation.  The  liver  holds  back  more  or  less  of  the  fat  taking 
this  route,  as  it  is  found  that  during  absorption  the  liver  cells  show 
an  accumulation  of  fat  droplets  in  their  interior.  J  The  amount  of 
fat  that  may  be  absorbed  from  the  intestines  varies  with  the 
nature  of  the  fat.  Experiments  show  that  the  more  fluid  fats,  such 

*  See  Moore  and  Rockwood,  "Journal  of  Physiology,"  21,  58,  1897;  also 
Moore  and  Parker,  "Proceedings,  Royal  Society,"  London,  58,  64,  1! 
t  See  Bloor, ' 
t  See  Frank, 


DIGESTION    AND    ABSORPTION    IN    THE    INTESTINES.  811 

as  olive  oil,  are  absorbed  more  completely,  that  is,  less  is  lost 
in  me  feces  than  in  the  case  of  the  more  solid  fats.  Compara- 
tive experiments  have  given  such  results  as  the  following:  Olive 
oil — absorption,  97.7  per  cent.;  goose  and  pork  fat,  97.5  per 
cent.;  mutton  fat,  90  to  92.5  per  cent.;  spermaceti,  15  per  cent. 
The  amount  of  fat  that  may  be  lost  in  the  feces  varies  also  with 
other  conditions.  If,  for  instance,  an  excess  is  taken  with  the 
food,  or  if  the  bile  flow  is  diminished  or  suppressed,  the  percentage 
in  the  feces  is  increased.  The  usual  amount  of  fat  allowed  as  a 
maximum  in  dietaries  is  from  100  to  120  gm.  daily. 

Absorption  of  Proteins. — Most  of  the  experimental  work  on 
record  shows  that  the  digested  proteins  are  absorbed  by  the  blood- 
vessels of  the  villi,  although  after  excessive  feeding  of  protein  a 
portion  may  be  taken  up  also  in  the  lymphatics.*  This  accepted 
belief  rests  upon  two  facts:  First  (Schmidt-Mulheim),  if  the  thoracic 
duct  (and  right  lymphatic  duct)  is  ligated,  so  as  to  shut  off  the  lym- 
phatic circulation,  an  animal  will  absorb  and  metabolize  the  usual 
amount  of  protein  as  is  indicated  by  the  urea  excreted  during  the  pe- 
riod. Second  (Munk),  if  a  fistula  of  the  thoracic  duct  is  established 
and  the  total  lymph  flow  from  the  intestines  is  collected  during 
the  period  of  absorption  after  a  diet  of  protein,  it  is  found  that  there 
is  no  increase  in  the  quantity  of  the  lymph  or  in  its  protein  contents. 
The  form  in  which  the  digested  protein  enters  the  blood  has  long 
been  a  matter  of  controversy,  t  On  the  view  that  we  have  adopted, 
namely,  that  the  protein  of  the  food  is  split  into  its  constituent 
amino-acids  by  the  successive  action  of  the  pepsin,  trypsin,  and 
erepsin,  we  should  expect  to  find  these  amino-acids  in  the  blood, 
unless,  indeed,  they  are  again  synthesized  to  protein  while  passing 
through  the  intestinal  wall.  It  is  only  in  recent  years  that  meth- 
ods have  been  devised  for  the  recognition  of  amino-acids  in  such  a 
liquid  as  blood,  t  The  application  of  these  methods  tends  to  sup- 
port the  view  that  the  amino-acids  enter  the  blood  as  such  without 
undergoing  synthesis.  Alanin  and  valin  have  been  obtained  from 
the  blood  in  crystalline  form,  and  histidin  has  been  recognized  by  its 
reaction.  §  Van  Slyke  and  Meyer  have  shown  that  in  the  blood 
of  dogs  amino-acids  are  constantly  present  in  small  amounts  (3  to 
5  mgms.  of  amino-acid  nitrogen  to  100  c.c.  of  blood),  and  that  after 
a  meal  of  meat  this  concentration  is  definitely  increased.  In  the 

*  See  Mendel,  "American  Journal  of  Physiology,"  2,  137,  1899. 

f  See  especially  Van  Slyke  and  Meyer,  "Journal  of  Biological  Chemistry," 
16, 197,  1913;  also  pp.  213  and  231. 

JFolin  and  Denis,  "Journal  of  Biological  Chemistry,"  11-87  and  161, 
1912;  and  Van  Slyke,  ibid.,  12,  399,  1912. 

$  Abel,  Rowntree,  and  Turner,  "Journal  of  Pharmacology  and  Exp.  Thera- 
peutics," 5,  611,  1914. 


812  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

light  of  recent  work,  especially  that  of  the  authors  last  named,  we 
may  suppose  that  the  normal  course  of  events  is  as  follows:  The 
digested  proteins  are  absorbed  as  amino-acids  and  distributed  to 
the  tissues  by  the  blood.  The  tissues  select  and  store  certain  of 
these  bodies,  and  probably  in  each  organ  subsequent  use  is  made  of 
them  to  build  up  new  tissue  or  to  repair  the  wastes  of  metabolism. 
That  is  to  say,  there  is  probably  no  especial  form  of  circulating 
protein  which  serves  as  a  pabulum  for  tissue-repair  and  growth,  but 
the  amino-acids  themselves  constitute  the  form  in  which  nitrogen 
food  is  presented  to  the  different  tissues,  just  as  dextrose  consti- 
tutes the  circulatory  form  of  carbohydrate  food.  Each  tissue  from 
the  amino-acids  offered  to  it  builds  up  its  own  form  of  protein, 
and  the  amino-acids  not  used  for  this  synthesis  may  be  deaminized 
and  then  employed  for  energy  purposes.  There  is  evidence  that 
in  the  liver  especially  many  of  the  amino-acids  arising  from  the 
digested  food  undergo  deaminization,  the  nitrogen  being  eliminated 
as  urea.  During  starvation  the  amino-acid  content  of  the  blood 
is  maintained,  probably  because  the  tissues  themselves  or  some  of 
them  undergo  self-digestion  or  autolysis  and  thus  furnish  food 
material  for  the  active  tissues. 

Examination  of  the  contents  of  the  small  intestine  at  its  junc- 
tion with  the  large  shows  that  under  normal  conditions  most  of  the 
protein  has  been  absorbed  before  reaching  this  point.  The  process 
is  continued  in  the  large  intestine,  modified  somewhat  by  bacterial 
action,  and  the  amount  that  finally  escapes  absorption  and  appears 
in  the  feces  varies,  in  perfectly  normal  individuals,  with  the  charac- 
ter of  the  protein  eaten.  According  to  Munk,*  the  easily  digestible 
animal  foods — such  as  milk,  eggs,  and  meat — are  absorbed  to  the 
extent  of  97  to  99  per  cent.,  while  with  vegetable  foods  the  utiliza- 
tion is  less  complete.  This  difference  is  not  due,  however,  to  any 
peculiarity  of  the  vegetable  proteins;  it  is  probably  an  incidental 
result  of  the  presence  of  the  indigestible  cellulose  found  in  our 
vegetable  foods.  It  is  stated  that  from  17  to  30  per  cent,  of  the 
protein  may  be  lost  in  the  feces  if  the  vegetable  food  is  in  such  form 
as  not  to  be  attacked  readily  by  the  digestive  secretions. 

Digestion  and  Absorption  in  the  Large  Intestine. — Observa- 
tions upon  the  secretions  of  the  large  intestine  have  been  made  upon 
human  beings  in  cases  of  anus  prseternaturalis,  in  which  the  lower 
portion  of  the  intestine  was  practically  isolated,  and  also  upon 
lower  animals,  in  which  an  artificial  anus  was  established  at  the 
end  of  the  small  intestine.  These  observations  all  indicate  that 
the  secretion  of  the  large  intestine,  while  it  contains  much  mucus 

*See  Munk,  "Ergebnisse  der  Physiologic,"  vol.  i.,  part  i.,  1902,  article 
"Resorption,"  for  literature  and  discussion. 


DIGESTION    AND    ABSORPTION    IN  THE    INTESTINES.  813 

and  shows  an  alkaline  reaction,  is  not  characterized  by  the  presence 
of  distinctive  enzymes.  When  the  contents  of  the  small  intestine 
pass  the  valve  they  still  contain  a  certain  amount  of  unabsorbed 
food  material.  As  was  stated  in  the  chapter  on  the  movements  of  the 
intestine,  these  contents  remain  a  long  time  in  the  large  intestine, 
and  since  they  contain  the  digestive  enzymes  received  in  the  duo- 
denum the  digestive  and  absorptive  processes  no  doubt  continue  as 
in  the  small  intestine.  This  general  fact  is  well  illustrated  in  experi- 
ments made  upon  dogs,  most  of  whose  small  intestine  (70  to  83 
per  cent.)  had  been  removed.*  These  animals  could  digest  and 
absorb  well,  and  formed  normal  feces,  provided  care  was  taken  with 
the  diet.  An  excess  of  fat  or  indigestible  material  caused  diarrhea 
and  serious  loss  of  food  material  in  the  feces.  An  interesting  feature 
in  the  large  intestine  is  the  marked  absorption  of  water.  In  the 
small  intestine  water  is  absorbed  no  doubt  in  large  quantities,  but 
its  loss  is  evidently  made  good  by  osmosis  or  secretion  of  water  into 
the  intestine,  since  the  contents  at  the  ileocecal  valve  are  quite 
as  fluid  as  at  the  pylorus.  In  the  large  intestine  the  absorption  of 
water  is  not  compensated  by  a  secretion;  the  material  loses  water 
rapidly  while  in  the  ascending  colon,  and  before  it  reaches  the 
descending  colon  it  has  acquired  the  consistency  of  the  feces.  The 
alkaline  reaction  of  the  contents  of  the  large  intestine  makes  a 
favorable  environment  for  the  growth  of  bacteria,  particularly  the 
putrefactive  bacteria  that  attack  protein  material.  Putrefaction 
is  a  normal  occurrence  in  the  large  intestine,  and  much  interest 
has  been  shown  in  its  extent  and  its  possible  physiological  signifi- 
cance. 

Bacterial  Action  in  the  Small  Intestine. — In  the  intestines  are 
found  numerous  bacteria  which  are  able  to  hydrolyze  the  food 
material,  particularly  the  carbohydrates  and  proteins.  Fermen- 
tation of  the  carbohydrates  gives  rise  to  a  number  of  organic 
acids,  such  as  lactic  and  acetic  acid,  but  none  of  the  products  of 
fermentation  can  be  regarded  as  distinctly  toxic.  Putrefaction 
of  the  protein  molecule,  on  the  other  hand,  gives  rise  to  a  number  of 
nitrogenous  split  products  that  are  supposed  to  have  a  toxic  action. 
Under  normal  conditions,  on  a  mixed  diet,  it  appears  that  in  the 
small  intestine  carbohydrate  fermentation  is  the  characteristic 
action  of  the  bacteria,  while  in  the  large  intestine,  protein  putre- 
faction undoubtedly  occurs.  There  has  been  considerable  discus- 
sion as  to  the  conditions  that  restrain  the  protein  putrefaction  in 
the  small  intestine.  It  has  been  pointed  out  that  some  of  the  bac- 
teria of  the  small  intestine,  Bacillus  coli  for  example,  do  not  cause 
protein  hydrolysis  as  long  as  carbohydrate  material  (sugar)  is 

*  Erlanger  and  Hewlett,  "American  Journal  of  Physiology  "  6,  1, 1902. 


814  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

present,*  so  that  the  mere  presence  of  carbohydrate  material 
serves  to  protect  the  protein  from  the  action  of  the  bacteria. 
In  addition,  as  long  as  carbohydrates  are  present  and  are  under- 
going fermentation,  the  organic  acids  produced  tend  to  neutralize 
the  alkalinity  of  the  intestinal  secretion,  and  may  even  give  an  acid 
reaction  to  the  intestinal  contents.  An  acid  reaction  is  unfavor- 
able to  the  activity  of  the  bacteria  that  attack  the  proteins,  and 
in  this  way,  under  conditions  of  a  normal  diet,  the  process  of  putre- 
faction in  the  small  intestine  is  warded  off.  From  this  standpoint 
it  would  seem  to  follow  that  the  nature  of  the  bacterial  activity 
in  the  small  intestine  will  vary  with  the  character  of  the  diet  and, 
moreover,  that  the  diet  may  be  chosen  intentionally  so  as  to 
favor  one  or  the  other  kind  of  bacterial  action. 

Bacterial  Action  in  the  Large  Intestine. — In  the  large  intestine 
protein  putrefaction  is  a  constant  and  normal  occurrence.  The 
reaction  here  is  stated  to  be  alkaline,  and  whatever  protein  may  have 
escaped  digestion  and  absorption  is  in  turn  acted  upon  by  the  bac- 
teria and  undergoes  so-called  putrefactive  fermentation.  The  split- 
ting up  of  the  protein  molecule  by  this  process  is  very  complete,  and 
differs  in  some  of  its  products  from  the  results  of  hydrolytic  cleavage 
as  caused  by  acids  or  by  trypsin.  The  list  of  end-products  of  putre- 
faction is  a  long  one.  Besides  peptones,  proteoses,  ammonia,  and 
the  various  amino-acids,  there  may  be  produced  such  substances  as 
indol,  skatol,  phenol,  phenylpropionic  and  phenylacetic  acids,  fatty 
acids,  carbon  dioxid,  hydrogen,  marsh  gas,  hydrogen  sulphid,  etc. 
Many  of  these  products  are  given  off  in  the  feces,  while  others  are 
absorbed  in  part  and  excreted  subsequently  in  the  urine.  In  this 
latter  connection  especial  interest  attaches  to  the  phenol,  indol,  and 
skatol.  Phenol  or  carbolic  acid,  C6H5OH,  after  absorption  is  com- 
bined with  sulphuric  acid,  to  form  an  ethereal  sulphate  (conjugated 
sulphate)  or  phenolsulphonic  acid,  C6H5OSO2OH,  and  in  this  form 
is  found  in  the  urine.  So  also  with  cresol.  The  indol,  C8H7N,  and 
skatol  (methyl-indol),  C9H9N,  are  also  absorbed,  undergo  oxidation  to 
indoxyl  and  skatoxyl,  and  are  then  combined  or  conjugated  with 
sulphuric  acid,  like  the  phenol,  and  in  this  form  are  found  in  the  urine 
— €8H6NOSO2OH,  or  indoxyl-sulphuric  acid,  and  C9H8NOSO2OH, 
skatoxyl-sulphuric  acid.  These  bodies  have  long  been  known  to 
occur  in  the  urine,  and  the  proof  that  they  arise  primarily  from  putre- 
faction of  protein  material  in  the  large  intestine  is  so  conclusive  as 
not  to  admit  of  any  doubt.  The  amount  to  which  they  occur  in 
the  urine  is,  therefore,  an  indication  of  the  extent  of  the  putrefaction 

*  See  Kendall,  "Boston  Med.  and  Surgical  Journal/'  1910,  163,  322,  and 
"Wisconsin  Med.  Journal,"  June,  1913. 


DIGESTION    AND    ABSORPTION    IN    THE    INTESTINES.  815 

in  the  large  intestine.  We  may  assume  that  the  indol  and  skatol 
arise  from  the  tryptophan  group  in  the  protein  molecule,  and  the 
phenol  and  cresol  from  the  ty rosin  and  phenylalanin.  There  is 
evidence  that  other  more  or  less  toxic  substances  belonging  to  the 
group  of  amines  are  produced  by  the  further  action  of  the  bacteria 
on  the  amino-acids  in  the  protein  molecule. 

The  general  relation  of  the  amines  to  the  amino-acids  may  be  expressed 
by  the  formula— 

RCH2CHNH2COOH  —  CO,  =  RCH2CH2NH2. 

As  a  group  they  have  a  drug-like  action  on  the  body  resembling  that  of 
epinephrin — that  is,  they  may  cause  a  rise  of  blood-pressure,  acceleration 
of  heart,  etc.  Some  of  the  amines  that  have  been  described  are  putrescin  or 
tetramethylendiamine  from  arginin,  cadaverin  or  pentamethylendiamine  from 
lysin,  imidazolethylamine  from  histidin,  indolethylamine  from  tryptophan, 
oxyphenylethylamine  from  tyrosin. 

Is  the  Putrefactive  Process  of  Physiological  Importance?— 

Recognizing  that  fermentation  by  means  of  bacteria  is  a  normal 
occurrence  in  the  gastro-intestinal  canal,  the  question  has  arisen 
whether  this  process  is  in  any  way  necessary  to  normal  digestion 
and  nutrition.  It  is  well  known  that  excessive  bacterial  action  may 
lead  to  intestinal  troubles,  such  as  diarrhea,  or  to  more  serious  inter- 
ference with  general  nutrition  owing  to  the  formation  of  toxic  prod- 
ucts. It  is,  however,  possible  that  some  amount  of  bacterial  action 
may  be  necessary  for  completely  normal  digestion.  As  a  special  case 
it  has  been  pointed  out  that  the  gastro-intestinal  tract  is  not  pro- 
vided with  enzymes  capable  of  acting  upon  cellulose,  a  material  that 
forms  such  an  important  constituent  of  vegetable  foods.  Bacteria, 
on  the  other  hand,  may  hydrolyze  the  cellulose  and  render  it  useful 
in  nutrition.  Leaving  aside  this  special  case,  the  question  as  to  the 
necessity  of  bacterial  action  has  been  investigated  directly  by  at- 
tempting to  rear  young  animals  under  perfectly  sterile  conditions. 
Nuttall  and  Thierfelder*  report  some  very  interesting  experiments 
upon  guinea-pigs  in  which  the  young  animals  from  birth  were  kept 
sterile  and  fed  with  perfectly  sterile  food.  They  found  that  the  ani- 
mals lived  and  increased  in  weight,  and  concluded,  therefore,  that  the 
intestinal  bacteria  are  not  necessary  to  normal  nutrition.  This  con- 
clusion is  supported  by  the  observations  of  Levin,  f  who  finds  that 
animals  in  the  Arctic  regions  in  many  cases  have  no  bacteria  in  their 
intestines.  Schottelius  t  reports  contrary  results  upon  chickens. 

*  Nuttall  and  Thierfelder,  "Zeitschrift  f.  physiol.  Chemie,"  21,  109,  1895; 
22,  62,  1896;  23,  231,  1897. 

t  Levin,  "Skandinavisches  Archiv  f.  Physiologic,"  16,  249,  1904. 
t  Schottelius,  "Archiv  f.  Hygiene,"  42,  48,  1902. 


816  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

When  kept  sterile  they  lost  steadily  in  weight  and  showed  normal 
growth  only  when  supplied  with  food  containing  bacteria.  The  idea 
that  the  relations  between  the  bacteria  and  the  animal  that  harbors 
them  constitutes  a  kind  of  symbiosis  in  which  each  derives  a  benefit 
from  the  other  has  certainly  not  been  demonstrated.  The  con- 
trary view,  that  bacterial  putrefaction  is  the  occasion  for  constant 
danger  to  the  human  organism,  has  been  stated  in  extreme  form, 
perhaps,  by  Metchnikoff.  According  to  this  author  the  constant 
production  and  absorption  of  bacterial  toxins  from  the  intestine  is 
one  of  the  important  causes  of  a  loss  of  resistance  on  the  part  of 
the  body  to  the  changes  which  bring  on  senescence  and  death. 
At  present  it  seems  wise  to  take  the  conservative  view  that  while 
the  presence  of  the  bacteria  confers  no  positive  benefit,  the  organ- 
ism has  adapted  itself  under  usual  conditions  to  neutralize  their 
injurious  action. 

Composition  of  the  Feces. — The  feces  differ  widely  in  amount 
and  in  composition  with  the  character  of  the  food.  Upon  a  diet 
composed  exclusively  of  meats,  they  are  small  in  amount  and  dark 
in  color;  with  an  ordinary  mixed  diet  the  amount  is  increased;  and 
it  is  largest  with  an  exclusively  vegetable  diet,  especially  with  vege- 
tables containing  a  large  amount  of  cellulose.  The  average 
weight  of  the  feces  in  twenty-four  hours  upon  a  mixed  diet  is 
given  as  170  gms.,  while  with  a  vegetable  diet  it  may  amount  to  as 
much  as  400  or  500  gms.  The  quantitative  composition,  therefore, 
varies  greatly  with  the  diet.  Qualitatively,  we  find  in  the  feces 
the  following  things:  (1)  Indigestible  material,  such  as  ligaments  of 
meat  or  cellulose  from  vegetables.  (2)  Undigested  material,  such  as 
fragments  of  meat,  starch,  or  fats  which  have  in  some  way  escaped 
digestion.  Naturally,  the  quantity  of  this  material  present  is  slight 
under  normal  conditions.  Some  fats,  however,  are  almost  always 
found  in  feces,  either  as  neutral  fats  or  as  fatty  acids,  and  to  a  small 
extent  as  calcium  or  magnesium  soaps.  The  quantity  of  fat  found  is 
increased  by  an  increase  of  the  fats  in  the  food  or  by  a  deficient 
secretion  of  bile.  (3)  Products  of  the  intestinal  secretions.  Evi- 
dence has  accumulated  in  recent  years*  to  show  that  the  feces  in 
man  on  an  average  diet  are  composed  in  part  of  the  unabsorbed 
material  of  the  intestinal  secretion.  The  nitrogen  of  the  feces,  for- 
merly supposed  to  represent  only  undigested  food,  seems  rather  to 
have  its  origin  largely  in  these  secretions,  together  with  the  cellular 
debris  thrown  off  from  the  walls  of  the  intestines.  (4)  Products  of 
bacterial  decomposition.  The  most  characteristic  of  these  products 
are  indol  and  skatol.  They  are  crystalline  bodies  possessing  a  dis- 
agreeable, fecal  odor;  this  is  especially  true  of  skatol,  to  which 

*Prausnitz,  "Zeitschrift  f.  Biologic,"  35,  335,  1897;  and  Tsuboi,  ibid.. 
p.  68. 


DIGESTION   AND    ABSORPTION    IN    THE    INTESTINES.  817 

the  odor  of  the  feces  is  mainly  due.  (5)  Cholesterin,  or  a  deriva- 
tive, which  is  found  always  in  small  amounts,  and  is  probably 
derived  from  the  bile.  (6)  Some  of  the  purin  bases,  especially 
guanin  arid  adenin.  (7)  Mucus  and  epithelial  cells  thrown  off 
from  the  intestinal  wall.  (8)  Pigment.  In  addition  to  the  color 
due  to  the  undigested  food  or  to  the  metallic  compounds  contained 
in  it,  there  is  normally  present  in  the  feces  a  pigment,  urobilin  or 
stercobilin,  derived  from  the  pigments  (bilirubin)  of  the  bile. 
Urobilin  is  formed  from  the  bilirubin  by  reduction  in  the  large 
intestine.  (9)  Inorganic  salts — salts  of  sodium,  potassium, 
calcium,  magnesium,  and  iron,  but  chiefly  the  last  three  together 
with  phosphoric  acid.  The  significance  of  the  calcium  and  iron 
salts  will  be  referred  to  in  a  subsequent  chapter,  when  speaking 
of  their  nutritive  importance.  (10)  Micro-organisms.  Great 
quantities  of  bacteria  of  different  kinds  are  found  in  the  feces. 

In  addition  to  the  feces,  there  is  found  often  in  the  large 
intestine  a  quantity  of  gas  that  may  also  be  eliminated  through 
the  rectum.  This  gas  varies  hi  composition.  The  following 
substances  have  been  found  at  one  time  or  another:  CH4,  CO2, 
H,  N,  H2S.  They  arise  mainly  from  the  bacterial  fermentation 
of  the  proteins,  although  some  of  the  N  may  be  derived  from  air 
swallowed  with  the  food. 

52 


CHAPTER  XLIV. 

PHYSIOLOGY  OF  THE  LIVER  AND  THE  SPLEEN. 

The  liver  plays  an  important  part  in  the  general  nutrition  of  the 
body.  Its  functions  are  manifold,  but  in  the  long  run  they  depend 
upon  the  properties  of  the  liver  cell,  which  constitutes  the  anatom- 
ical and  physiological  unit  of  the  organ,  although  there  is  histo- 
logical  evidence  that  some  of  the  endothelial  cells  of  the  capillaries 
of  the  liver  have  marked  phagocytic  properties,  and  it  is  possible 
that  their  activity  may  play  a  contributory  part  in  some  of  the 
functions  of  the  liver,  for  example,  in  the  destruction  of  the  red 
corpuscles  that  precedes  the  formation  of  bile  pigments.  The  liver 
cells  are  seemingly  uniform  in  structure  throughout  the  whole  sub- 
stance of  the  liver,  but  to  understand  clearly  the  different  functions 
they  fulfil  one  must  have  a  clear  idea  of  their  anatomical  relations 
to  one  another  and  to  the  blood-vessels,  the  lymphatics,  and  the 
bile-ducts.  The  histology  of  the  liver  lobule,  and  the  relationship 
of  the  portal  vein,  the  hepatic  artery,  and  the  bile-duct  to  the  lobule, 
must  be  obtained  from  the  text-books  upon  histology  and  anatomy. 
It  is  sufficient  here  to  recall  the  fact  that  each  lobule  is  supplied 
with  blood  coming  in  part  from  the  portal  vein  and  in  part  from  the 
hepatic  artery.  The  blood  from  the  former  source  contains  the 
soluble  materials  absorbed  from  the  alimentary  canal,  such  as  sugar 
and  the  split  products  (amino-acids)  of  protein,  and  these  absorbed 
products  are  submitted  to  the  metabolic  activity  of  the  liver  cells 
before  reaching  the  general  circulation.  The  hepatic  artery  brings 
to  the  liver  cells  the  arterialized  blood  sent  out  to  the  systemic  cir- 
culation from  the  left  ventricle.  In  addition,  each  lobule  gives 
origin  to  the  bile  capillaries  which  arise  between  the  separate  cells 
and  which  carry  off  the  bile  formed  within  the  cells.  In  accordance 
with  these  facts,  the  physiology  of  the  liver  cell  falls  naturally  into 
two  parts, — one  treating  of  the  formation,  composition,  and  physio- 
logical significance  of  bile,  and  the  other  dealing  with  the  metabolic 
changes  produced  in  the  mixed  blood  of  the  portal  vein  and  the 
hepatic  artery  as  it  flows  through  the  lobules.  In  this  latter  divi- 
sion the  main  phenomena  to  be  studied  are  the  formation  of  urea 
and  the  formation  and  significance  of  glycogen,  but  it  cannot  be 
doubted  that  the  liver  possesses  other  important  metabolic  func- 
tions which  at  present  are  imperfectly  understood,  such,  for 
example,  as  its  relations  to  the  production  of  fibrinogen  and  of 
antithrombin,  which  have  been  referred  to  in  the  section  on  Blood. 

Bile. — From  a  physiological  standpoint,  bile  is  partly  an  excre- 
tion carrying  off  certain  waste  products,  and  partly  a  digestive  secre- 

818 


PHYSIOLOGY    OF    THE    LIVER   AND    SPLEEN.  819 

tion  playing  an  important  role  in  the  absorption  of  fats,  and  possibly 
in  other  ways.  Bile  is  a  continuous  secretion,  but  in  animals  possess- 
ing a  gall-bladder  its  ejection  into  the  duodenum  is  intermittent. 
Bile  is  easily  obtained  from  living  animals  by  establishing  a  fistula 
of  the  bile-duct  or,  as  seems  preferable,  of  the  gall-bladder.  The 
latter  operation  has  been  performed  a  number  of  times  on  human 
beings.  In  some  cases  the  entire  supply  of  bile  has  been  diverted  in 
this  way  to  the  exterior,  and  it  is  an  interesting  physiological  fact 
that  such  patients  may  continue  to  enjoy  fair  health,  showing  that, 
whatever  part  the  bile  takes  normally  in  digestion  and  absorption, 
its  passage  into  the  intestine  is  not  absolutely  necessary  to  the  nu- 
trition of  the  body.  It  should  be  stated,  however,  that  this  usual 
belief  has  been  denied,  so  far  at  least  as  the  dog  is  concerned. 
Whipple  and  Hooper*  state  that  when  the  bile  is  wholly  excluded 
from  the  intestinal  tract  the  animal  shows  intestinal  disorders  and 
dies  within  a  month.  The  quantity  of  bile  secreted  during  the  day 
has  been  estimated  for  human  beings  of  average  weight  (43  to  73 
kgms.)  as  varying  between  500  and  800  c.c.  This  estimate  is  based 
upon  observations  on  cases  of  biliary  fistula,  j  Chemical  analyses 
of  the  bile  show  that,  in  addition  to  the  water  and  salts,  it  contains 
bile  pigments,  bile  acids,  cholesterin,  lecithin,  neutral  fats  and  soaps, 
sometimes  a  trace  of  urea,  and  a  mucilaginous  nucleo-albumin  for- 
merly designated  improperly  as  mucin.  The  last-mentioned  sub- 
stance is  not  formed  in  the  liver  cells,  but  is  added  to  the  bile  by  the 
mucous  membrane  of  the  bile-ducts  and  gall-bladder.  The  quantity 
of  these  substances  present  in  the  bile  varies  in  different  animals 
and  under  different  conditions.  As  an  illustration  of  their  relative 
importance  in  human  bile  and  of  the  limits  of  variation,  the  two 
following  analyses  by  Hammarsten  J  may  be  quoted  : 

i.  ii. 

Solids  .............................  2.520  2.840 

Water  .............................  97.480  97.160 

Mucin  and  pigment  .................   0.529  0.9TO 

Bile  salts  ..........................  0.931  0.814 

Taurocholate  .......................  0.3034  0.053 

Glycocholate  ................  .  ......  0.6276  0.761 

Fatty  acids  from  soap  ..............  0.1230  0.024 

Cholesterin  ........................  0.0630  0.096 


......  ...................  0.0220  0.1286 

Soluble  salts  .......................  0.8070  0.8051 

Insoluble  salts  .....................  0.0250  0.0411  . 

The  color  of  bile  varies  in  different  animals  according  to  the  pre- 

*  Hooper  and  Whipple,  "American  Journal  of  Physiology,"  40,  332,  1916. 

f  Copeman  and  Winston,  "Journal  of  Physiology,"  10,  213,  1889;  Robson, 
"Proceedings  of  the  Royal  Society,"  London,  47,  499,  1890;  Pfaff  and  Balch, 
"Journal  of  Experimental  Medicine,"  2,  49,  1897. 

j  Reported  in  "Centralblatt  f.  Physiologic,"  1894,  No.  8.  For  other 
analyses  consult  Rosenbloom,  "Journal  of  Biological  Chemistry,"  14,  241,  1913. 


820  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

ponderance  of  one  or  the  other  of  the  main  bile  pigments,  bilirubin 
and  biliverdin.  The  bile  of  carnivorous  animals  has  usually  a 
golden  color,  owing  to  the  presence  of  bilirubin,  while  that  of  the  her- 
bivora  is  a  bright  green  from  the  biliverdin.  The  color  of  human 
bile  seems  to  vary:  according  to  some  authorities,  it  is  yellow  or 
golden  yellow,  and  this  seems  especially  true  of  the  bile  as  found  in 
the  gall-bladder  of  the  cadaver;  according  to  others,  it  is  of  a  dark- 
olive  color  with  the  greenish  tint  predominating.  Its  reaction  is 
feebly  alkaline,  and  its  specific  gravity  varies  in  human  bile  from 
1.050  or  1.040  to  1.010.  Human  bile  does  not  give  a  distinctive 
absorption  spectrum,  but  the  bile  of  some  herbivora,  after  exposure 
to  the  air  at  least,  gives  a  characteristic  spectrum. 

Bile  Pigments. — Bile,  according  to  the  animal  from  which  it  is 
obtained,  contains  one  or  the  other,  or  a  mixture,  of  the  two 
pigments,  bilirubin  and  biliverdin.  Indeed,  it  is  probable  that 
in  some  animals  at  least  still  other  pigments,  such  as  urobilin, 
may  be  present  in  the  bile,  together  with  the  bilirubin  or  biliverdin. 
Biliverdin  is  supposed  to  stand  to  bilirubin  in  the  relation  of  an 
oxidation  product.  Bilirubin  is  given  the  formula  Ci6Hi8N203, 
or  C32H36N4O6,  and  biliverdin,  Ci6Hi8N2O4  or  C32H36N408,  the 
latter  being  prepared  readily  from  the  former  by  oxidation.  These 
pigments  give  a  characteristic  reaction,  known  as  "Gmelin's  reac- 
tion," with  nitric  acid  containing  some  nitrous  acid  (nitric  acid 
with  a  yellow  color) .  If  a  drop  of  bile  and  a  drop  of  nitric  acid  are 
brought  into  contact,  the  former  undergoes  a  succession  of  color 
changes,  the  order  being  green,  blue,  violet,  red,  and  reddish  yellow. 
The  play  of  colors  is  due  to  successive  oxidations  of  the  bile  pig- 
ments; starting  with  bilirubin,  the  first  stage  (green)  is  due  to  the 
formation  of  biliverdin.  The  pigments  formed  in  some  of  the 
other  stages  have  been  isolated  and  named.  The  reaction  is  very 
delicate,  and  it  is  often  used  to  detect  the  presence  of  bile  pigments 
in  other  liquids — urine,  for  example.  The  bile  pigments  originate 
from  hemoglobin.  This  origin  was  first  indicated  by  the  fact  that 
in  old  blood  clots  or  in  extravasations  there  was  found  a  crystalline 
product,  the  so-called  "hematoidin,"  which  was  undoubtedly  de- 
rived from  hemoglobin,  and  which  upon  more  careful  examina- 
tion was  proved  to  be  identical  with  bilirubin.  It  is  supposed 
that  when  the  blood-corpuscles  disintegrate  the  liberated  hemo- 
globin is  converted  by  the  liver  cells  to  an  iron-free  compound, 
bilirubin  or  biliverdin.  The  bilirubin  is  formed  from  the  hematin 
of  the  hemoglobin  by  a  process  which  involves  the  splitting  off 
of  its  iron.  It  is  very  significant  that  the  iron  separated  by  this 
means  from  the  hematin  is,  for  the  most  part,  retained  in  the 
liver,  a  small  portion  only  being  secreted  in  the  bile.  It  seems 
probable  that  the  iron  held  back  in  the  liver  is  again  used  in  some 


PHYSIOLOGY    OF    THE    LIVER    AND    SPLEEN.  821 

way  to  make  new  hemoglobin  in  the  hematopoietic  organs.  Since 
the  hematin  constitutes  only  4  per  cent,  of  the  hemoglobin,  it  is  evi- 
dent that  in  the  production  of  the  bilirubin  a  considerable  amount 
of  globin  must  be  formed  also,  but  nothing  is  known  of  the  fate  of 
this  portion  of  the  molecule.  The  general  view  has  been  that  hem- 
oglobin liberated  from  disintegrated  red  corpuscles  serves  as  the 
sole  source  of  bile  pigment,  but  some  recent  observers*  have  ques- 
tioned this  assumption.  They  show  that  the  amount  of  bile  pig- 
ment excreted  varies  with  the  nature  of  the  diet,  being  markedly 
increased,  in  dogs,  by  a  carbohydrate  diet,  and  reduced  by  a  pure 
meat  diet.  This  fact  would  seem  to  indicate  some  relationship 
between  liver  activity  and  pigment  formation.  The  bile  pig- 
ments are  carried  in  the  bile  to  the  duodenum  and  are  mixed 
with  the  food  in  its  long  passage  through  the  intestine.  Under 
normal  conditions  neither  bilirubin  nor  biliverdin  occurs  in  the 
feces,  but  in  their  place  is  found  a  reduction  product,  urobilin, 
formed  in  the  large  intestine,  probably  in  consequence  of  the 
activity  of  the  bacteria.  Moreover,  it  is  believed  that  some  of 
the  bile  pigment  is  reabsorbed  as  it  passes  along  the  intestine,  is 
carried  to  the  liver  in  the  portal  blood,  and  is  again  eliminated. 
That  this  action  occurs,  or  may  occur,  has  been  made  probable 
by  experiments  of  Wertheimer*  on  dogs.  It  happens  that  sheep's 
bile  contains  a  pigment  (cholohematin)  that  gives  a  characteristic 
spectrum.  If  some  of  this  pigment  is  injected  into  the  mesenteric 
veins  of  a  dog  it  is  eliminated  while  passing  through  the  liver,  and 
can  be  recognized  unchanged  in  the  bile.  The  value  of  this  "cir- 
culation of  the  bile,"  so  far  as  the  pigments  are  concerned,  is  not 
apparent. 

Bile  Acids. — "  Bile  acids"  is  the  name  given  to  two  organic  acids, 
glycocholic  and  taurocholic}  which  are  always  present  in  bile,  and, 
indeed,  form  very  important  constituents  of  that  secretion;  they 
occur  in  the  form  of  their  respective  sodium  salts.  In  human  bile 
both  acids  are  usually  found,  but  the  proportion  of  taurocholate 
is  variable,  and  in  some  cases  it  may  be  absent  altogether. 
Among  herbivora  the  glycocholate  predominates,  as  a  rule,  although 
there  are  some  exceptions ;  among  the  carnivora,  on  the  other  hand, 
taurocholate  occurs  usually  in  greater  quantities,  and  in  the  dog's 
bile  it  is  present  alone.  Glycocholic  acid  has  the  formula  C26H43NO6, 
and  taurocholic  acid  the  formula  C26H45NSO7.  Each  of  them  can 
be  obtained  in  the  form  of  crystals.  When  boiled  with  acids  or  alka- 
lies these  acids  take  up  water  and  undergo  hydrolytic  cleavage,  the 
reaction  being  represented  by  the  following  equations: 

*  Whipple  and  Hooper,  "American  Journal  of  Physiology,"  40,  349,  1916. 
t  "Archives  de  physiologie  normale  et  pathologique,"  1892,  p.  577. 


822  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 


O.    +     H20  =  C^H^O,     +     CH?(NH?)COOH. 

Glycochoiic  acid.  Cholic  acid.     Glycocoll  (amino-acetic-acid). 


+   H2O  =  C^H^O.  +  C2H4NH2SO2OH 

Taurocholic  acid.  Cholic  acid.        Taurin  (amino-ethyl- 

sul  phonic  acid). 

These  reactions  indicate  that  the  bile  acids  are  probably  formed  by 
a  reverse  process,  in  the  one  case  by  a  conjugation  of  glycocoll  with 
cholic  acid,  in  the  other  by  a  union  of  taurin  and  cholic  acid.  In 
this  synthesis  the  reaction  takes  place  between  the  carboxyl  group 
of  the  cholic  acid  and  the  amino-group  of  the  glycocoll  or  taurin, 
as  may  be  represented  by  the  following  equation  : 

C23H3903COOH  +  NH2CH2COOH  —  H2O  =  C23H39O3CONHCH2COOH 

Cholic  acid.  Glycocoll.  Glycochoiic  acid. 

Cholic  acid  or  its  compounds,  the  bile-acids,  are  usually  detected  in 
suspected  liquids  by  the  well-known  Pettenkofer  reaction.  As 
usually  performed,  the  test  is  made  by  adding  to  the  liquid  a  few 
drops  of  a  10  per  cent,  solution  of  cane-sugar  and  then  strong  sul- 
phuric acid.  The  latter  must  be  added  carefully  and  the  tempera- 
ture be  kept  below  70°  C.  If  bile  acids  are  present,  the  liquid  as- 
sumes a  red-violet  color.  It  is  now  known  that  the  reaction  consists 
in  the  formation  of  a  substance  (furfurol)  by  the  action  of  the  acid 
on  sugar,  which  then  reacts  with  the  bile  acids.  The  bile  acids  are 
formed  directly  in  the  liver  cells.  This  fact,  which  was  for  a  long 
time  the  subject  of  discussion,  has  been  demonstrated  in  recent 
years  by  an  important  series  of  researches  made  upon  birds.  It  has 
been  shown  that  if  the  bile-duct  is  ligated  in  these  animals,  the  bile 
formed  is  reabsorbed  and  bile  acids  and  pigments  may  be  detected 
in  the  urine  and  the  blood.  If,  however,  the  liver  is  completely 
extirpated,  then  no  trace  of  either  bile  acids  or  bile  pigments  can 
be  found  in  the  blood  or  the  urine,  showing  that  these  substances 
are  not  formed  elsewhere  in  the  body  than  in  the  liver.  It  is 
more  difficult  to  ascertain  from  what  substances  they  are  formed. 
The  chemical  origin  of  the  cholic  acid  is  not  definitely  known.  The 
glycocoll  is  one  of  the  amino-acids  formed  by  the  hydrolysis  of 
proteins,  and  the  liver  gets  a  supply  of  this  material  after  meals 
through  the  portal  blood,  although,  in  all  probability,  it  can  be 
formed  also  within  the  liver  cells  by  autolytic  processes.  In  any 
case,  so  far  as  it  is  present  in  the  bile  as  glycocholic  acid,  it  repre- 
sents a  loss  or  excretion  of  so  much  protein  nitrogen.  The  taurin  is 
likewise  derived  from  protein  and  presumably  from  the  cystein 
grouping  in  the  protein  molecule.  By  oxidation  the  cystein  may  be 
converted  to  cysteinic  acid: 


PHYSIOLOGY    OF    THE    LIVER    AND    SPLEEN.  823 

CH2SHCHNH2COOH  +  3O  =  CH2SO2OHCHNH2COOH; 

Cystein.  Cysteinic  acid. 

and  by  loss  of  CO2  this  is  converted  to  taurin : 

CH2SO2OHCHNH2COOH  —  CO2  =  CH2SO2OHCH2NH2. 

A  circumstance  of  considerable  physiological  significance  is  that 
these  acids  or  their  decomposition  products  are  absorbed  in  part  from 
the  intestine  and  are  again  secreted  by  the  liver;  as  in  the  case  of  the 
pigments,  there  is  an  intestinal-hepatic  circulation.  The  value  of  this 
reabsorption  may  lie  in  the  fact  that  the  bile  acids  constitute  a  very 
efficient  stimulus  to  the  bile-secreting  activity  of  the  cells,  being  one 
of  the  best  of  cholagogues,  or  it  may  be  that  it  economizes  material. 
From  what  we  know  of  the  history  of  the  bile  acids  it  is  evident  that 
they  are  not  to  be  considered  solely  as  excreta:  they  have  some 
important  function  to  fulfill.  The  following  suggestions  as  to  their 
value  have  been  made :  In  the  first  place,  they  serve  as  a  menstruum 
for  dissolving  the  cholesterin  which  is  constantly  present  in  the  bile; 
secondly,  they  facilitate  greatly  the  splitting  and  the  absorption  of 
fats  in  the  intestine.  It  is  an  undoubted  fact  that  when  bile  is 
shut  off  from  the  intestine  the  absorption  of  fats  is  very  much 
diminished,  and  it  has  been  shown  that  this  action  of  the  bile  in 
fat  absorption  is  due  chiefly  to  the  presence  of  the  bile-acids,  and 
in  the  same  way  the  known  activating  influence  of  bile  upon  the 
activity  of  pancreatic  lipase  has  been  traced  to  the  bile-acids.  The 
bile-acids,  the  taurocholate,  at  least,  possess  the  property  of  pre- 
cipitating proteins  in  acid  solutions.  This  property  probably  ex- 
plains the  fact  that  the  acid  chyme  as  it  passes  into  the  duodenum 
is  precipitated  by  coming  into  contact  with  the  bile,  a  fact  which 
has  long  been  known,  although  its  physiological  significance  is  not 
clear. 

Cholesterin  or  Cholesterol. — Cholesterin  is  a  non-nitrogenous 
substance  of  the  formula  C27H46O.  (See  p.  78.)  It  is  a  constant 
constituent  of  the  bile,  although  it  occurs  in  variable  quantities. 
Cholesterin  is  very  widely  distributed  in  the  body,  being  found 
especially  in  the  white  matter  (medullary  substance)  of  nerve- 
fibers.  It  seems,  moreover,  to  be  a  constant  constituent  of  all 
animal  and  plant  cells.  It  is  assumed  that  cholesterin  is  not 
formed  in  the  liver,  but  that  it  is  eliminated  by  the  liver  cells 
from  the  blood,  which  collects  it  from  the  various  tissues  of 
the  body.  This  is  at  least  a  possible  explanation  of  its  occur- 
rence in  the  bile,  for  it  seems  certain  that  the  cholesterin  is  a 
constant  constituent  of  the  blood,  either  as  such  or  in  the  form 
of  an  ester,  that  is  to  say,  in  combination  with  a  fatty  acid,  such  as 
stearic  acid.  Some  authors  suggest,  however,  that  in  the  disso- 


824  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

lution  of  red  corpuscles  that  takes  place  in  the  liver  the  cho- 
lesterin  liberated  from  the  stroma  of  the  corpuscles  forms  the 
source  of  the  cholesterin  found  in  the  bile.  That  it  is  an  excretion 
is  indicated  by  the  fact  that  it  is  eliminated  in  the  feces,  but  here 
again  the  opposite  view  has  been  suggested  that  the  cholesterin  is 
in  part  at  least  reabsorbed  and  used  again  in  the  formation  of 
new  tissue.*  Cholesterin  is  insoluble  in  water  or  in  dilute  saline 
liquids,  and  is  held  in  solution  in  the  bile  by  means  of  the  bile-acids. 
Provisionally  we  may  regard  it,  so  far  as  its  occurrence  in  the  bile  is 
concerned,  as  a  waste  product  of  cellular  disintegration  which  is 
eliminated  in  the  feces.  It  is  excreted  also  through  the  skin,  in 
the  sebaceous  and  sweat  secretions,  and  in  the  milk. 

Lecithin,  Fats,  and  Nucleo-albumin. — Lecithin,  C^Hgo- 
NPO9,  is  a  compound  of  glycerophosphoric  acid  with  fatty  acid 
radicals  (stearic,  oleic,  or  palmitic)  and  a  nitrogenous  base,  cholin 
(see  p.  78).  When  hydrolyzed  by  boiling  with  alkali  it  splits 
up  into  these  three  substances.  It  is  found  generally  as  such, 
or  in  combination,  in  all  cells,  and  evidently  plays  some  as  yet 
unknown  part  in  cell  metabolism.  It  occurs  in  largest  quantity 
in  the  white  matter  of  the  nervous  system.  In  the  liver  it  occurs 
to  a  considerable  extent  both  as  lecithin  and  in  a  more  complex 
combination  with  a  carbohydrate  residue,  a  compound  designated 
as  jecorin.  So  far  as  it  is  found  in  the  bile,  it  represents  possibly 
a  waste  product  derived  from  the  liver  or  from  the  body  at  large, 
although  it  is  possible  that  it  may  undergo  hydrolysis  in  the  intes- 
tine and  be  absorbed  in  the  form  of  its  split  products.  Little  is 
known  of  its  precise  physiological  significance.  According  to 
Hewlett  and  others  it  may  serve  to  activate  the  lipase  of  the  pan- 
creatic secretion. 

The  special  importance,  if  any,  of  the  small  proportion  of  fats 
and  fatty  acids  in  the  bile  is  unknown.  The  ropy,  mucilaginous 
character  of  bile  is  due  to  the  presence  of  a  body  formed  in  the  bile- 
ducts  and  gall-bladder.  This  substance  was  formerly  designated 
as  mucin,  but  it  is  now  known  that  in  ox  bile  at  least  it  is  not  a  true 
mucin,  but  a  nucleo-albumin  (see  appendix).  Hammarsten  reports 
that  in  human  bile  some  true  mucin  is  found.  Outside  the  fact  that 
it  makes  the  bile  viscous,  this  constituent  is  not  known  to  possess  any 
especial  physiological  significance. 

The  Secretion  of  the  Bile. — Numerous  experiments  have  been 
made  to  ascertain  whether  or  not  the  secretion  of  bile  is  controlled 
by  a  special  set  of  secretory  fibers.  The  secretion  itself  is  continuous, 
but  varies  in  amount  under  different  conditions.  These  conditions 
may  be  controlled  experimentally  in  part.  It  has  been  shown,  for 
example,  that  stimulation  of  the  spinal  cord  or  splanchnic  nerve 
diminishes  the  flow  of  bile,  while  section  of  the  splanchnic  branches 

*  See  Gardner  and  co-workers,  "Proc.  Royal  Soc.,"  B,  vols.  81  and  82, 1910. 


PHYSIOLOGY    OF    THE    LIVER    AND    SPLEEN.  825 

may  cause  an  increased  flow.  These  and  similar  actions  are  ex- 
plained, however,  by  their  effect  on  the  blood-flow  through  the  liver. 
The  splanchnics  carry  vasomotor  nerves  to  the  liver,  and  section  or 
stimulation  of  these  nerves  will  therefore  alter  the  circulation  in  the 
organ.  Since  the  secretion  increases  when  the  blood-flow  is  increased 
and  vice  versa,  it  is  believed  that  in  this  case  no  special  secretory 
nerve  fibers  exist.  The  metabolic  processes  in  the  liver  cells  which 
produce  the  secretion  probably  go  on  at  all  times,  but  they  are 
increased  when  the  blood-flow  is  increased.  We  may  believe,  there- 
fore, that  the  quantity  of  the  bile  secretion  varies  with  the  quantity 
and  composition  of  the  blood  flowing  through  the  liver,  and  that 
the  blood  contains  normally  chemical  substances  which  stimulate 
the  liver  cells  to  secrete  bile.  It  is  stated  on  the  basis  of  experi- 
mental evidence*  that  when  the  supply  of  portal  blood  is  cut  off 
the  amount  of  bile  formed  is  greatly  reduced,  and  that,  therefore, 
it  is  possible  that  the  substances  from  which  bile  is  formed  or 
which  serve  to  stimulate  the  production  of  bile  are  furnished  chiefly 
by  the  portal  blood.  Substances  which  stimulate  the  formation  of 
bile  are  designated  as  cholagogues.  The  therapeutical  agents  cap- 
able of  giving  this  action  are  still  a  subject  of  controversy.  On 
the  physiological  side-  the  following  facts  are  accepted :  Any  agent 
that  causes  an  hemolysis  of  red  corpuscles  increases  the  flow  of 
bile,  or  the  same  effect  is  produced  if  a  solution  of  hemoglobin  is 
injected  directly  into  the  blood.  This  result  is  in  harmony  with  the 
views  already  stated  regarding  the  significance  of  the  bile  pigments 
as  an  excretory  product  of  hemoglobin.  The  cholagogue  whose 
action  is  most  distinct  and  prolonged  is  bile  itself.  When  fed 
or  injected  directly  into  the  circulation,  bile  causes  an  undoubted  in- 
crease in  the  secretion.  This  effect  is  due  both  to  the  bile  acids  and 
bile  pigments.  Since  the  bile  acids  have  a  hemolytic  effect  on  red 
corpuscles,  it  might  at  first  be  assumed  that  their  action  as  chola- 
gogues  is  due  indirectly  to  this  circumstance.  The  action  of  the 
bile  acids  is,  however,  much  more  pronounced  than  that  of  other 
hemolytic  agents,  and  it  seems  certain,  therefore,  that  they  exert 
a  specific  effect  on  the  liver  cells.  So  also  it  is  stated  (Weinberg) 
that  peptones  and  proteoses  have  a  marked  stimulating  effect, 
and  since  these  substances  may  be  brought  to  the  liver  in  the 
portal  blood,  it  is  possible  that  they  act  as  stimuli  under  normal 
conditions.  Lastly,  there  is  evidence  that  the  secretin,  whose  ac- 
tion upon  the  pancreatic  secretion  has  been  described,  exerts  a  sim- 
ilar effect  upon  the  secretion  of  bile.  Statements  differ  somewhat  in 
regard  to  the  extent  of  this  action,  but  it  seems  to  be  certain  that, 
when  acids  (0.5  per  cent.  HC1)  are  injected  into  the  duodenum  or  upper 
part  of  the  jejunum,  the  secretion  of  bile  is  increased;  and,  since 

*  Voegtlin  and  Bernheim,  "Journal  of  Pharmacology  and  Exp.  Therapeu- 
tics," 2,  455,  1910. 


826 


PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 


this  effect  takes  place  when  the  nervous  connections  are  severed,  the 
effect,  as  in  the  case  of  the  pancreatic  secretion,  is  explained  by 
assuming  that  the  acid  converts  prosecretin  to  secretin,  and  this 
latter  after  absorption  into  the  blood  acts  upon  the  liver  cells.* 
A  similar  effect  may  be  obtained  by  injecting  secretin  directly  into 
the  blood.  Since  during  a  meal  the  stomach  normally  ejects  acid 
chyme  into  the  duodenum,  the  importance  of  this  secretin  reaction 
in  adapting  the  secretion  of  bile  to  the  period  of  digestion  is  evident. 
The  Ejection  of  Bile  into  the  Duodenum — Function  of  the 
Gall-bladder. — Although  the  bile  is  formed  more  or  less  continu- 
ously, it  enters  the  duodenum  periodically  during  the  time  of  digestion. 
The  secretion  during  the  intervening  periods  is  prevented  from  enter- 
ing the  duodenum  apparently  by  the  fact  that  the  opening  of  the 


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Fig.  297. — Curves  showing  the  velocity  of  secretion  of  bile  into  the  duodenum  on 
(1)  a  diet  of  milk,  uppermost  curve;  (2)  a  diet  of  meat,  middle  curve;  (3)  a  diet  of  bread, 
lowest  curve.  The  divisions  on  the  abscissa  represent  intervals  of  thirty  minutes;  the 
figures  on  the  ordinates  represent  the  volume  of  secretion  in  cubic  centimeters. — (Brunt.) 

common  bile-duct  is  closed  by  a  sphincter.  The  secretion,  therefore, 
backs  up  into  the  gall-bladder.  According  to  Bruns.  t  no  bile  appears 
in  the  duodenum  as  long  as  the  stomach  is  empty.  When,  how- 
ever, a  meal  is  taken,  the  ejection  of  the  chyme  into  the  duode- 

*  See  Falloise,  quoted  in  Maly's  "  Jahres-bericht  der  Thier-chemie,"  33, 
611,  1904. 

t  "Archives  des  sciences  biologiques,"  7,  87,  1899. 


PHYSIOLOGY    OF    THE    LIVER    AND    SPLEEN.  827 

num  is  followed  by  an  ejection  of  bile.*  It  would  seem,  therefore, 
that  each  gush  of  chyme  into  the  duodenum  excites,  probably  by 
reflex  action,  a  contraction  of  the  gall-bladder,  and  an  inhibition 
of  the  sphincter  closing  the  opening  into  the  intestine. 

An  interesting  application  of  this  fact  has  been  made  in  surgical  practice. 
After  operations  upon  the  gall-bladder  trouble  is  experienced  at  times  owing 
to  the  failure  of  the  fistulous  opening  to  heal,  so  that  there  is  constant  oozing 
of  gall.  It  is  found  that  frequent  feeding  of  the  patient  facilitates  the  per- 
manent closure  of  the  fistula,  because  apparently  the  sphincter  is  kept  inhibited 
and  the  pressure  in  the  gall-bladder  is  lowered. 

The  substances  in  the  chyme  that  are  responsible  for  the  stim- 
ulation have  been  investigated  by  Bruns.  He  finds  that  acids, 
alkalies,  and  starches  are  ineffective,  and  concludes  that  the  reflex 
is  due  to  the  proteins  and  fats  or  some  of  the  products  of  their 
digestion.  The  gall-bladder  has  a  muscular  coat  of  plain  muscle, 
and  records  made  of  its  contractions  show  that  the  force  exerted 
is  quite  small.  According  to  Freese,t  the  maximal  contraction 
does  not  exceed  that  necessary  to  overcome  the  hydrostatic  pressure 
of  a  column  of  water  220  mms.  in  height, — a  force,  therefore,  which 
is  about  equivalent  to  the  secretion  pressure  of  bile  as  determined 
by  Heidenhain.  The  innervation  of  the  gall-bladder  and  gall-ducts 
has  been  studied  especially  by  Doyon,  J  It  would  seem,  from  the 
experiments  made  by  this  author  together  with  later  experiments 
reported  by  others,!  that  the  bladder  receives  both  motor  and  in- 
hibitory fibers  by  way  of  the  splanchnic  nerves.  These  fibers  emerge 
from  the  spinal  cord  in  the  roots  of  the  sixth  thoracic  to  the  first 
lumbar  spinal  nerve,  and  pass  to  the  celiac  plexus  by  way  of  the 
splanchnic  nerves.  Motor  fibers  may  occur  also  in  the  vagi .  Sensory 
fibers  capable  of  causing  a  reflex  constriction  or  dilatation  of  the 
bladder  are  found  in  both  the  vagus  and  splanchnic  nerves.  Stim- 
ulation of  the  central  end  of  the  cut  splanchnic  causes  a  dilatation 
of  the  bladder  (reflex  stimulation  of  the  inhibitory  fibers),  while 
stimulation  of  the  central  end  of  the  vagus  causes  a  contraction 
of  the  bladder  and  a  dilatation  (inhibition)  of  the  sphincter  muscle 
at  the  opening  of  the  common  duct  into  the  intestine.  These 
latter  movements  are  the  ones  that  occur  during  normal  digestion, 
and  we  may  assume,  therefore,  that  in  the  normal  reflex  emptying 
of  the  gall-bladder  the  afferent  path  for  the  reflex  is  formed  by 
the  vagus  fibers  while  the  efferent  path  is  through  the  splanchnic 
nerves. 

Effect  of  Complete  Occlusion  of  the  Bile-duct. — When  the 
flow  of  bile  is  prevented  by  ligation  of  the  bile-duct,  or  when  this 

*See  also  Klodnizki,  quoted  from  Maly's  "Jahres-bericht  der  Thier- 
chemie,"  33,  617,  1904. 

(•"Johns  Hopkins  Hosp  tal  Bulletin,"  June,  1905. 
j  Doyon,  "Archives  de  physiologic,"  1894,  p.  19. 
§  Bainbridge  and  Dale,  "Journal  of  Physiology,"  1905,  vol.  xxxiii.,  138. 


828  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

duct  is  occluded  by  pathological  changes  the  bile  eventually  gets 
into  the  blood,  producing  a  condition  of  jaundice  (icterus).  There 
has  been  much  discussion  as  to  whether  the  bile  is  absorbed  directly 
into  the  blood  from  the  liver  cells  or  the  liver  lymph-spaces,  or 
whether  it  is  carried  to  the  blood  by  way  of  the  lymph-vessels  and 
thoracic  duct.*  Experimental  evidence  points  to  both  possibili- 
ties. The  increased  pressure  in  the  bile  system  leads  possibly  to 
a  rupture  of  the  delicate  bile  capillaries,  and  the  bile  thus  escapes 
into  the  lymph-spaces.  From  these  spaces  it  may  be  absorbed 
directly  by  the  blood-vessels  of  the  liver,  or  it  may  be  carried  off 
in  the  lymph-stream  toward  the  thoracic  duct.  • 

General  Physiological  Importance  of  Bile. — The  physiological 
value  of  bile  has  been  referred  to  in  speaking  of  its  several  constitu- 
ents. It  is  probably  of  importance  both  as  a  medium  of  excretion 
and  as  a  digestive  secretion.  Its  value  from  the  former  stand- 
point we  know  little  about.  Certain  of  its  constituents,  the  bile 
pigments,  cholic  acid,  cholesterin,  and  lecithin,  may  appear  in  the 
feces  more  or  less  modified,  but  on  the  other  hand  these  substances 
may  be  reabsorbed  in  part  from  the  intestine,  so  that  it  is  difficult 
to  say  in  how  far  they  are  to  be  regarded  as  excretory  products. 
On  the  experimental  side  it  can  be  shown  that  a  number  of  dyes 
when  introduced  into  the  blood  are  eliminated  or  excreted  by  way  of 
the  bile  as  well  as  through  the  urine,  a  fact  which  indicates  that  the 
liver  may  act  as  an  excretory  organ.  As  a  digestive  secretion,  the 
most  important  function  attributed  to  the  bile  is  the  part  it  takes  in 
the  digestion  and  absorption  of  fats.  It  accelerates  greatly  the  action 
of  the  lipase  of  pancreatic  juice  in  splitting  the  fats  to  fatty  acids  and 
glycerin,  and  it  aids  materially  in  the  absorption  of  the  products 
of  this  hydrolysis.  A  number  of  observers  have  shown  that  when  a 
permanent  biliary  fistula  is  made,  and  the  bile  is  thus  prevented 
from  reaching  the  intestinal  canal,  a  large  proportion  of  the  fat  of 
the  food  escapes  absorption  and  is  found  in  the  feces.  This  action  of 
the  bile  may  be  referred  directly  to  the  fact  that  the  bile  acids  serve 
as  a  solvent  for  the  fats  and  fatty  acids.  It  was  formerly  believed 
that  bile  is  also  of  great  importance  in  restraining  the  processes  of 
putrefaction  in  the  intestine.  It  was  asserted  that  bile  is  an  efficient 
antiseptic,  and  that  this  property  comes  into  use  normally  in  prevent- 
ing excessive  putrefaction.  Bacteriological  experiments  made  by  a 
number  of  observers  have  shown,  however,  that  bile  itself  has  very 
feeble  antiseptic  properties,  as  is  indicated  by  the  fact  that  it  putrefies 
readily.  The  free  bile  acids  and  cholalic  acid  do  have  a  direct  retard- 
ing effect  upon  putrefactions  outside  the  body;  but  this  action  is  not 
very  pronounced,  and  has  not  been  demonstrated  satisfactorily  for 
bile  itself.  It  seems  to  be  generally  true  that  in  cases  of  biliary  fistula 

*  See  Mendel  and  Underbill  for  literature,  "American  Journal  of  Phys- 
iology," 14,  252,  1905. 


PHYSIOLOGY    OF    THE    LIVER    AND    SPLEEN. 

the  feces  have  a  very  fetid  odor  when  meat  and  fat  are  taken  in  the 
food.  But  the  increased  putrefaction  in  these  cases  may  possibly  be 
an  indirect  result  of  the  withdrawal  of  bile.  It  has  been  suggested, 
for  instance,  that  the  deficient  absorption  of  fat  that  follows  upon  the 
removal  of  the  bile  results  in  the  protein  and  carbohydrate  material 
becoming  coated  with  an  insoluble  layer  of  fat,  so  that  the  penetration 
of  the  digestive  enzymes  is  retarded  and  greater  opportunity  is  given 
for  the  action  of  bacteria.  We  may  conclude,  therefore,  that,  while 
there  does  not  seem  to  be  sufficient  warrant  at  present  for  believing 
that  the  bile  exerts  a  direct  antiseptic  action  upon  the  intestinal 
contents,  nevertheless  its  presence  limits  in  some  way  the  extent  of 
putrefaction. 

Glycogen. — One  of  the  most  important  functions  of  the  liver  is 
the  formation  of  glycogen.  This  substance  was  found  in  the  liver  in 
1857  by  Claude  Bernard,  and  is  one  of  several  brilliant  discoveries 
made  by  him.  Glycogen  has  the  formula  (C6H10O5)n,  which  is  also 
the  general  formula  given  to  vegetable  starch ;  glycogen  is  therefore 
frequently  spoken  of  as  "  animal  starch."  It  gives,  however,  a  port- 
wine-red  color  with  iodin  solutions,  instead  of  the  familiar  deep  blue 
of  vegetable  starch,  and  this  reaction  serves  to  detect  glycogen  not 
only  in  its  solutions,  but  also  in  the  liver  cells.  Glycogen  is  readily 
soluble  in  water,  and  the  solutions  have  a  characteristic  opalescent 
appearance.  Like  starch,  glycogen  is  acted  upon  by  ptyalin  and 
other  diastatic  enzymes,  and  the  end-products  are  apparently  the 
same — namely,  maltose,  or  maltose  and  some  dextrin,  or  else  dex- 
trose, depending  upon  the  enzyme  used.  Under  the  influence  of 
acids  it  may  be  hydrolyzed  at  once  to  dextrose.* 

Occurrence  of  Glycogen  in  the  Liver. — Glycogen  can  be 
detected  in  the  liver  cells  microscopically.  If  the  liver  of  a  dog  is 
removed  twelve  or  fourteen  hours  after  a  hearty  meal,  hardened  in 
alcohol,  and  sectioned,  the  liver  cells  are  found  to  contain  clumps 
of  clear  material  which  give  the  iodin  reaction  for  glycogen.  Even 
when  distinct  aggregations  of  the  glycogen  cannot  be  made  out,  its 
presence  in  the  cells  is  shown  by  the  red  reaction  with  iodin.  By 
this  simple  method  one  can  demonstrate  the  important  fact  that  the 
amount  of  glycogen  in  the  liver  increases  after  meals  and  decreases 
again  during  the  fasting  hours,  and  if  the  fast  is  sufficiently  prolonged 
it  may  disappear  altogether.  This  fact  is,  however,  shown  more 
satisfactorily  by  quantitative  determinations,  by  chemical  means, 
of  the  total  glycogen  present.  The  amount  of  giycogen  in  the 
liver  is  quite  variable,  being  influenced  by  such  conditions  as  the 
character  and  amount  of  the  food,  muscular  exercise,  body  tem- 
perature, drugs,  etc.  From  determinations  made  upon  various 

*  The  extensive  literature  of  glycogen  is  collected  and  reviewed  by  Cre- 
mer  in  the  "Ergebnisse  der  Physiologic,"  vol.  1,  part  i,  1902;  and  by  Pfliiger. 
"Archiv  f.  die  gesammte  Physiologic,"  96,  1,  1903. 


830  PHYSIOLOGY    OF   DIGESTION    AND    SECRETION. 

animals  it  may  be  said  that  the  average  amount  lies  between  1.5  and 
4  per  cent,  of  the  weight  of  the  liver.  But  this  amount  may  be  in- 
creased greatly  by  feeding  upon  a  diet  largely  made  up  of  carbohy- 
drates, it  is  said  that  in  the  dog  the  total  amount  of  liver  glycogen 
may  be  raised  to  17  per  cent.,  and  in  the  rabbit  to  27  per  cent.,  by 
this  means,  while  it  is  estimated  for  man  (Neumeister)  that  the  quan- 
tity may  be  increased  to  at  least  10  per  cent.  It  is  usually  believed 
that  glycogen  exists  as  such  in  the  liver  cells,  being  deposited  in  the 
substance  of  the  cytoplasm.  Reasons  have  been  brought  forward 
to  show  that  this  is  not  strictly  true,  and  that  the  glycogen  is  prob- 
ably held  in  some  sort  of  weak  chemical  combination.  It  has  been 
shown,  for  instance,  that  although  glycogen  is  easily  soluble  in  cold 
water,  it  can  not  be  extracted  readily  from  the  liver  cells  by  this  agent. 
One  must  use  hot  water,  salts  of  the  heavy  metals,  and  other  similar 
agents  that  may  be  supposed  to  break  up  the  combination  in  which 
the  glycogen  exists.  For  practical  purposes,  however,  we  may  speak 
of  the  glycogen  as  lying  free  in  the  liver-cells,  just  as  we  speak  of 
hemoglobin  existing  as  such  in  the  red  corpuscles,  although  it  is 
probably  held  in  some  sort  of  combination. 

Origin  of  Glycogen. — To  understand  clearly  the  views  held  as 
to  the  origin  of  liver  glycogen,  it  is  necessary  to  describe  briefly  the 
effect  of  the  different  foodstuffs  upon  its  formation. 

Effect  of  Carbohydrates  on  the  Amount  of  Glycogen. — The  amount 
of  glycogen  in  the  liver  is  affected  very  quickly  by  the  quantity  of  car- 
bohydrates in  the  food.  If  the  carbohydrates  are  given  in  excess,  the 
supply  of  glycogen  may  be  increased  largely  beyond  the  average 
amount  present,  as  has  been  stated  above.  Investigation  of  the  differ- 
ent sugars  has  shown  that  dextrose,  levulose,  saccharose  (cane-sugar), 
and  maltose  are  unquestionably  direct  glycogen-formers, — that  is, 
glycogen  is  formed  directly  from  them  or  from  the  products  into 
which  they  are  converted  during  digestion.  The  bulk  of  our  car- 
bohydrate food  reaches  the  liver  as  dextrose,  or  as  dextrose  and  levu- 
lose, and  these  forms  of  sugar  may  be  converted  into  glycogen  in  the 
liver  cells  by  a  simple  process  of  dehydration  and  condensation, 
such  as  may  be  represented  in  substance  by  the  formula — 

n(C6H1206) '-  n(H20)  =  (C6H10O5)n. 

There  is  no  doubt  that  both  dextrose  and  levulose  increase  markedly 
the  amount  of  glycogen  in  the  liver;  and,  since  cane-sugar  is  inverted 
in  the  intestine  before  absorption,  it  also  must  be  a  true  glycogen- 
former, — a  fact  that  has  been  abundantly  demonstrated  by  direct 
experiment.  Lusk*  has  shown,  however,  that,  if  cane-sugar  is  in- 
jected under  the  skin,  it  has  a  very  feeble  effect  in  the  way  of  increas- 
ing the  amount  of  glycogen  in  the  liver,  since  under  these  conditions 
it  is  probably  absorbed  into  the  blood  without  undergoing  inversion. 

*  Voit,  "Zeitschrift  f.  Biologie,"  28,  285,  18C1. 


PHYSIOLOGY    OF    THE    LIVER   AND    SPLEEN.  831 

Experiments  with  subcutaneous  injection  of  lactose  gave  similar 
results,  and  it  is  generally  believed  that  the  liver  cells  cannot  convert 
the  double  sugars  Jo  glycogen,  at  least  not  readily;  hence  the  value 
of  the  hydrolysis  of  these  sugars  in  the  alimentary  canal  before 
absorption.  We  may  assume,  therefore,  that  dextrose,  levulose,  and 
galactose  are  the  true  glycogen-formers  that  occur  normally  in  the 
blood,  and  that  the  disaccharids  (cane-sugar,  milk-sugar,  etc.)  and 
the  polysaccharids  (starches)  are  true  glycogen-formers  to  the  ex- 
tent that  they  are  converted  into  dextrose,  levulose,  or  galactose. 
Effect  of  Protein  on  Glycogen  Formation. — In  his  first  studies 
upon  glycogen  Bernard  asserted  that  it  may  be  formed  from  protein 
material.  Since  that  time  some  doubt  has  been  thrown  on  the 
possibility  of  this  transformation,  but  it  may  be  said,  perhaps,  that 
the  trend  of  all  recent  work  indicates  that  the  amino-acids  yielded 
by  proteins  may  serve  as  a  starting-point  for  the  formation  of 
glycogen.  Direct  evidence  has  been  obtained  for  this  latter  state- 
ment by  feeding  experiments  with  glycin,  alanin,  aspartic  and  glu- 
tamic  acid,  prolin,  serin,  cystin,  and  arginin.*  It  may  be  assumed 
that  the  amino-acids  that  undergo  this  change  in  the  liver  are  first 
deprived  of  their  nitrogen  by  a  process  of  deaminization  and  that 
the  non-nitrogenous  organic  acid  remaining  is  synthesized  to  sugar. 
From  alanin,  for  example,  by  deaminization,  lactic  acid  would  be 
produced — 

CH3CHNH2COOH  +  H2O  =  CH3CHOHCOOH  +  NH3, 

and  it  is  believed  that  the  Tactic  acid  can  be  synthesized  to  sugar — 
2C3H6O3  =  C6H12O6. 

The  conclusion  to  be  drawn  from  such  experiments  is  strengthened 
by  clinical  experience  upon  human  beings  suffering  from  diabetes. 
In  severe  forms  of  this  disease  the  carbohydrate  material  of  the 
food  escapes  oxidation  in  the  body  and  is  secreted  unchanged  in 
the  urine.  If  under  these  conditions  the  individual  is  given  an 
exclusively  protein  diet,  sugar  still  continues  to  appear  in  the 
urine,  and  it  would  seem  that  this  sugar  can  only  arise  from  the 
protein  food.  In  the  similar  condition  of  severe  glycosuria  that 
may  be  produced  by  the  use  of  phlorizin  it  has  been  shown  that  the 
animal  continues  to  excrete  sugar  even  when  fed  on  protein  alone 
or  when  starved.  Under  such  conditions  the  amount  of  dextrose  in 
the  urine  bears  a  definite  ratio  to  the  amount  of  nitrogen  excreted 
D  :  N  ::  3.65  :  1  (Lusk),  which  would  indicate  that  both  arise 
from  the  breaking  down  of  the  protein  molecule.  So  also  the  fact 
that  during  prolonged  starvation,  lasting  for  forty  or  even  ninety 

*  Dakin,  "Journal  of  Biological  Chemistry,"  14,  321,  1913. 


832  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

days,  the  blood  retains  a  practically  constant  composition  in  sugar 
indicates  that  this  material  is  being  formed  from  either  the  protein 
or  tat-supply  of  the  body.  Other  considerations  tend  to  exclude  the 
fat,  and  we  are,  therefore,  led  to  the  belief  that  the  protein  can  give 
rise  to  sugar  in  the  body. 

Effect  of  Fats  upon  Glycogen  'Formation. — A  large  number  of 
substances  have  been  found  by  some  observers  to  increase  the  store 
of  glycogen  in  the  liver.  In  some  of  these  cases  at  least  it  is  evident 
that  the  substance  is  not  a  direct  glycogen-former  in  the  sense  that 
the  material  is  itself  converted  to  glycogen.  It  may  increase  the 
supply  of  liver  glycogen  in  some  indirect  way, — for  example,  by 
diminishing  the  consumption  of  glycogen  in  the  body.  The  most 
important  substance  in  this  connection  from  a  practical  standpoint 
is  fat.  Whether  or  not  the  body  can  convert  fats  into  sugar  or 
glycogen  is  a  question  about  which  at  present  there  is  a  difference 
of  opinion,  but  the  balance  of  evidence  is  against  the  possibility 
of  the  conversion  of  the  fats  (fatty  acids)  to  sugar.  Cremer, 
however,  has  furnished  apparent  proof  that  glycerin  acts  as  a 
direct  glycogen  or  sugar-former.  When  fed,  especially  in  the  dia- 
betic condition,  it  causes  an  increase  in  the  sugar  which  cannot 
be  explained  as  a  result  of  protein  metabolism.  Since  in  the  body 
neutral  fats  are  normally  split  into  glycerin  and  fatty  acid,  the  fact 
that  glycerin  can  be  converted  to  sugar  seems  to  carry  with  it  the 
admission  that  fats  may  contribute  directly  to  sugar  production. 
Whether  the  synthesis  of  sugar  (or  glycogen)  from  glycerin  is, 
so  to  speak,  a  normal  process  or  occurs  only  under  special  condi- 
tions, cannot  be  decided  at  present.  Since,  however,  the  glycerin 
radicle  constitutes  but  a  small  fraction  of  the  fat  molecule,  the 
quantitative  importance  of  a  change  of  this  kind  cannot  be  very 
great  under  any  circumstances. 

The  Function  of  Glycogen — The  Glycogenic  Theory. — The 
meaning  of  the  formation  of  glycogen  in  the  liver  has  been  the 
subject  of  much  discussion.  The  view  advanced  first  by  Ber- 
nard is  the  one  now  most  generally  accepted.  According  to 
Bernard,  glycogen  forms  a  temporary  reserve  supply  of  carbo- 
hydrate material  that  is  laid  up  in  the  liver  during  digestion  and 
is  gradually  made  use  of  in  the  intervals  between  meals.  During 
digestion  the  carbohydrate  food  is  absorbed  into  the  blood  of  the 
portal  system  as  dextrose  or  as  dextrose,  levulose,  and  galactose. 
If  these  sugars  passed  through  the  liver  unchanged,  the  contents 
of  the  systemic  blood  in  sugar  would  be  increased  perceptibly, 
giving  the  condition  designated  as  hyperglycemia  and  the  excess  of 
sugar  would  be  excreted  by  the  kidneys.  But  as  the  blood  from 
the  digestive  organs  passes  through  the  liver  the  excess  of  sugar  is 
abstracted  by  the  liver  cells,  is  dehydrated  to  make  glycogen,  and  is 


PHYSIOLOGY    OF    THE    LIVER   AND    SPLEEN.  833 

retained  in  the  cells  in  this  form  for  a  short  period.  An  objection 
has  been  made  to  this  part  of  the  glycogenic  hypothesis  by  Pavy 
on  the  ground  that  if  all  the  carbohydrates  of  a  meal  were  absorbed 
into  the  blood  as  free  sugar,  a  condition  of  hyperglycemia  and  glyco- 
suria  must  evidently  result,  because  the  liver  cannot  be  supposed 
to  handle  the  large  amount  of  sugar  derived  from  the  carbohydrates 
of  an  ordinary  meal.  We  know  that  glycosuria  does  occur  when 
the  carbohydrates  are  eaten  in  excess  (alimentary  glycosuria)  for 
this  very  reason.  But  within  what  we  may  call  the  normal 
limits  of  a  carbohydrate  diet  it  seems  most  probable  that  the 
contents  of  the  portal  vein  never  rise  much  above  the  usual  level, 
since  the  carbohydrate  is  absorbed  slowly  during  a  period  of  four 
to  five  hours,  and  during  this  period  a  very  large  amount  of  blood 
must  flow  through  the  intestines,  as  much  perhaps  in  five  hours 
as  180  to  190  liters,  if  one  may  apply  to  man  the  results  of  Burton- 
Opitz,  obtained  for  the  dog,  namely,  a  flow  of  31  c.c.  per  minute 
for  each  100  gms.  of  intestine.  There  is,  therefore,  no  reason  to 
suppose  that  the  power  of  the  liver  to  convert  the  dextrose  to  gly- 
cogen  is  overtaxed  by  the  amount  of  sugar  brought  to  it  dur- 
ing digestion.  From  time  to  time  the  glycogen  of  the  liver 
is  reconverted  into  sugar  (dextrose)  and  is  given  off  to  the  blood. 
By  this  means  the  percentage  of  sugar  in  the  systemic  blood 
is  kept  nearly  constant  (0.1  to  0.2  per  cent.)  and  within  limits 
best  adapted  to  the  use  of  the  tissues.  The  great  importance  of  the 
formation  of  glycogen  and  the  consequent  conservation  of  the  sugar 
supply  of  the  tissues  is  evident  when  we  consider  the  nutritive  value 
of  carbohydrate  food.  Carbohydrates  form  the  bulk  of  our  usual 
diet,  and  the  proper  regulation  of  the  supply  to  the  tissues  is,  there- 
fore, of  vital  importance  in  the  maintenance  of  a  normal,  healthy 
condition.  The  second  part  of  this  theory,  which  holds  that  the 
glycogen  is  reconverted  to  dextrose,  is  supported  by  observations 
upon  livers  removed  from  the  body.  It  has  been  found  that  shortly 
after  the  removal  of  the  liver  the  supply  of  glycogen  begins  to  dis- 
appear and  a  corresponding  increase  in  dextrose  occurs.  Within  a 
comparatively  short  time  all  the  glycogen  is  gone  and  only  dextrose 
is  found.  It  is  for  this  reason  that  in  the  estimation  of  glycogen  in  the 
liver  it  is  necessary  to  mince  the  organ  and  to  throw  it  into  boiling 
water  as  quickly  as  possible,  since  by  this  means  the  liver  cells  are 
killed  and  the  conversion  of  the  glycogen  is  stopped.  How  the  gly- 
cogen is  changed  to  dextrose  by  the  liver  is  a  matter  not  fully  ex- 
plained. According  to  most  authors,  the  conversion  is  due  to  an 
enzyme  produced  in  the  liver.  Extracts  of  liver,  as  of  some  other 
tissues,  yield  an  enzyme  (glycogenase)  that  changes  glycogen  to  dex- 
trose.* The  conversion  of  stored  glycogen  to  sugar  and  its  dis- 

*  Tebb,  "Journal  of  Physiology,"  22,  423,  1897-98. 
53 


834  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

charge  into  the  blood  is  designated  sometimes  as  the  process  of 
glycogenolysis.  It  has  been  shown  that  the  process  may  be  facil- 
itated by  a  number  of  conditions,  such  as  acidosis  or  diminution  in 
the  alkali  reserve  of  the  blood,  strong  emotions,  or  an  increased 
secretion  of  epinephrin.  These  reactions  may  be  considered  as 
adaptations  suited  to  increase  the  efficiency  of  the  organism.  Thus, 
under  the  influence  of  strong  emotions  (Cannon),  the  glycogen,  to 
use  the  current  expression,  is  mobilized,  that  is  to  say,  is  converted 
to  sugar  so  that  it  may  be  utilized  as  a  source  of  energy  in  increased 
muscular  work.  In  this  description  of  the  origin  and  meaning  of 
the  liver  glycogen  reference  has  been  made  only  to  the  glycogen  de- 
rived directly  from  digested  carbohydrates.  The  glycogen  derived 
from  protein  foods,  once  it  is  formed  in  the  liver,  has,  of  course^ 
the  same  functions  to  fulfil.  It  is  converted  into  sugar,  and 
eventually  is  oxidized  in  the  tissues.  For  the  sake  of  completeness 
it  may  be  well  to  add  that  some  of  the  sugar  of  the  blood  formed 
from  the  glycogen,  when  an  excess  is  eaten  beyond  the  energy 
needs  of  the  tissues,  may  be  converted  into  fat  in  the  adipose 
tissues  instead  of  being  burnt,  and  in  this  way  it  may  be  retained 
in  the  body  as  a  reserve  supply  of  food  of  a  more  stable  character. 
Glycogen  in  the  Muscles  and  other  Tissues. — The  history  of 
glycogen  is  not  complete  without  some  reference  to  its  occurrence  in 
the  muscles.  Glycogen  is,  in  fact,  found  in  various  places  in  the  body, 
and  is  widely  distributed  throughout  the  animal  kingdom.  It  occurs, 
for  example,  in  leucocytes,  in  the  placenta,  in  the  rapidly  growing 
tissues  of  the  embryo,  and  in  considerable  abundance  in  the  oyster 
and  other  molluscs.  But  in  our  bodies  and  in  those  of  the  mammals 
generally  the  most  significant  occurrence  of  glyeogen,  outside  the 
liver,  is  in  the  voluntary  muscles,  of  which  glycogen  forms  a  normal 
constituent.  It  has  been  estimated  that  the  percentage  of  glycogen 
in  resting  muscle  varies  from  0.5  to  0.9  per  cent.,  and  that  in  the 
musculature  of  the  whole  body  there  may  be  contained  an  amount 
of  glycogen  equal  to  that  in  the  liver  itself.  Muscular  tissue,  as 
well  as  liver  tissue,  has  a  glycogenetic  function — that  is,  it  is  cap- 
able of  laying  up  a  supply  of  glycogen  from  the  sugar  brought 
to  it  by  the  blood.  The  glycogenetic  function  of  muscle  has  been 
demonstrated  directly  by  Kulz,*  who  has  shown  that  an  isolated 
muscle  irrigated  with  an  artificial  supply  of  blood  to  which  dextrose 
is  added  is  capable  of  changing  the  dextrose  to  glycogen,  as  shown 
by  the  increase  in  the  latter  substance  in  the  muscle  after  irriga- 
tion. Muscle  glycogen  is  to  be  looked  upon  as  a  temporary  and 
local  reserve  supply  of  material;  so  that,  while  we  have  in  the 
liver  a  large  general  depot  for  the  temporary  storage  of  glycogen  for 
the  use  of  the  body  at  large,  the  muscular  tissue,  which,  considering 
*  Kulz,  "Zeitschrift  f.  Biologie,"  72,  237,  1890. 


PHYSIOLOGY    OF    THE    LIVER    AND    SPLEEN.  835 

its  bulk,  is  the  most  active  tissue  of  the  body  from  the  standpoint 
of  energy  production,  is  also  capable  of  laying  up  in  the  form  of  gly- 
cogen  any  excess  of  sugar  brought  to  it.  The  fact  that  glycogen 
occurs  so  widely  in  the  rapidly  growing  cells  of  embryos  indicates  that 
this  glycogenetic  function  may  at  times  be  exercised  by  any  tissue. 

Conditions  Affecting  the  Supply  of  Glycogen  in  Muscle  and 
Liver. — In  accordance  with  the  view  given  above  of  the  general  value 
of  glycogen — namely,  that  it  is  a  temporary  reserve  supply  of 
carbohydrate  material  that  may  be  rapidly  converted  to  sugar  and 
oxidized  with  the  liberation  of  energy — it  is  found  that  the  supply 
of  glycogen  is  greatly  affected  by  conditions  calling  for  increased 
metabolism  in  the  body.  Muscular  exercise  quickly  exhausts  the 
supply  of  muscle  and  liver  glycogen,  provided  it  is  not  renewed 
by  new  food.  Observations  on  isolated  muscles  have  shown 
definitely  that  the  local  supply  of  glycogen  is  diminished  when  the 
muscle  is  made  to  contract  (see  p.  66).  In  a  starving  animal 
glycogen  finally  disappears,  except  perhaps  in  traces,  but  this 
disappearance  occurs  much  sooner  if  the  animal  is  made  to  use  its 
muscles  at  the  same  time.  It  has  been  shown  also  by  Morat  and 
Dufourt  that  if  a  muscle  has  been  made  to  contract  vigorously 
it  takes  up  much  more  sugar  from  an  artificial  supply  of  blood  sent 
through  it  than  a  similar  muscle  which  has  been  resting  ;  on  the 
other  hand,  it  has  been  found  that  if  the  nerve  of  one  leg  is  cut 
so  as  to  paralyze  the  muscles  of  that  side  of  the  body,  the  amount 
of  glycogen  is  greater  in  these  muscles  than  in  those  of  the  other 
leg  that  have  been  contracting  meantime  and  using  up  their  gly- 
cogen. The  further  history  of  glycogen  is  considered  in  the  section 
on  Nutrition. 

Formation  of  Urea  in  the  Liver. — The  nitrogen  contained  in 
the  protein  material  of  our  food  is  finally  eliminated,  mainly  in  the 
form  of  urea.  It  has  been  definitely  proved  that  the  i^rea  is  not 
formed  in  the  kidneys,  the  organs  that  eliminate  it.  It  has  long  been 
considered  a  matter  of  the  greatest  importance  to  ascertain  in  what 
organ  or  tissues  urea  is  formed.  Investigations  have  gone  so  far  as 
to  demonstrate  that  it  arises  in  part  at  least  in  the  liver;  hence  the 
property  of  forming  urea  must  be  added  to  the  other  important  func- 
tions of  the  liver  cell.  Schroder  *  performed  a  number  of  experi- 
ments in  which  the  liver  was  taken  from  a  freshly  killed  dog  and 
irrigated  through  its  blood-vessels  with  a  supply  of  blood  obtained 
from  another  dog.  If  the  supply  of  blood  was  taken  from  a  fasting 
animal,  then  circulating  it  through  the  isolated  liver  was  not  followed 
by  any  increase  in  the  amount  of  urea  contained  in  it.  If,  on  the 
contrary,  the  blood  was  obtained  from  a  well-fed  dog,  the  amount 

*  Archiv  f.  experimentelle  Pathologic  und  Pharmakologie,"  15,  364,  1882, 
and  19,  373,  1885. 


836  PHYSIOLOGY   OF    DIGESTION    AND   SECRETION. 

of  urea  contained  in  it  was  distinctly  increased  by  passing  it  through 
the  liver,  thus  indicating  that  the  blood  of  an  animal  alter  digestion 
contains  something  that  the  liver  can  convert  to  urea.  It  is  to  be 
noted,  moreover,  that  this  power  is  not  possessed  by  all  the  organs, 
since  blood  from  well-fed  animals  showed  no  increase  in  urea  after 
being  circulated  through  an  isolated  kidney  or  muscle.  As  further 
proof  of  the  urea-forming  power  of  the  liver  Schroder  found  that 
if  ammonium  carbonate  was  added  to  the  blood  circulating  through 
the  liver — to  that  from  the  fasting  as  well  as  from  the  well-nourished 
animal — a  very  decided  increase  in  the  urea  was  always  obtained. 
It  follows  from  the  last  experiment  that  the  liver  cells  are  able  to 
convert  carbonate  of  ammonium  into  urea.  The  reaction  may  be 
expressed  by  the  equation  (NH4)2CO3-2H2O  =  CON2Ht.  Schon- 
dorff  *  in  some  later  work  showed  that  if  the  blood  of  a  fasting  dog 
is  irrigated  through  the  hind  legs  of  a  well-nourished  animal,  no 
increase  in  urea  in  the  blood  can  be  detected ;  but  if  the  blood,  after 
irrigation  through  the  hind  legs,  is  subsequently  passed  through  the 
liver,  a  marked  increase  in  urea  results.  Obviously,  the  blood  in  this 
experiment  derives  something  from  the  tissues  of  the  leg  which  the 
tissues  themselves  cannot  convert  to  urea,  but  which  the  liver  cells 
can.  Finally,  in  some  remarkable  experiments  upon  dogs  made  by 
four  investigators  (Hahn,  Massen,  Nencki,  and  Pawlow),  which  are 
described  more  fully  in  the  next  chapter,  it  was  shown  that  when  the 
liver  is  practically  destroyed  there  is  a  distinct  diminution  in  the 
urea  of  the  urine.  In  birds  uric  acid  takes  the  place  of  urea  as  the 
main  nitrogenous  excretion  of  the  body,  and  Minkowski  has  shown 
that  in  them  removal  of  the  liver  is  followed  by  an  important 
diminution  in  the  amount  of  uric  acid  excreted.  From  experiments 
such  as  these  it  is  safe  to  conclude  that  urea  is  formed  in  the  liver 
and  is  then  given  to  the  blood  and  excreted  by  the  kidney.  In 
treating  of  the  physiological  history  of  urea  an  account  will  be  given 
of  the  views  proposed  with  regard  to  the  antecedent  substance  or 
substances  from  which  the  liver  produces  urea. 

Physiology  of  the  Spleen. — Much  has  been  said  and  written 
about  the  spleen,  but  we  are  yet  in  the  dark  as  to  the  distinctive 
function  or  functions  of  this  organ.  The  few  facts  that  are  known 
may  be  stated  briefly  without  going  into  the  details  of  theories  that 
have  been  offered  at  one  time  or  another.  The  older  experimenters 
demonstrated  that  this  organ  may  be  removed  from  the  body  with- 
out serious  injury  to  the  animal.  An  increase  in  the  size  of  the 
lymph-glands  and  hyperplasia  of  the  bone-marrow  has  been  stated 
to  occur  after  extirpation;  but  this  is  denied  by  others,  and,  whether 
true  or  not,  it  gives  no  decisive  clue  to  the  normal  functions  of  the 
spleen.  Observations  upon  splenectomized  dogs  indicate  that  it 

*  PfliigerVArchiv  f.  die  gesammte  Physiologic,"  54,  420,  1893. 


PHYSIOLOGY    OF    THE    LIVER    AND    SPLEEN.  837 

has  some  connection  with  the  life-history  of  the  red  corpuscles  and 
of  the  hemoglobin  contained  in  them.*  Splenectomy  is  followed 
always  by  an  anemic  condition  that  lasts,  however,  for  a  short 
period  only.  After  some  months  the  number  of  red  corpuscles  re- 
turns to  normal.  On  the  other  hand,  injection  of  splenic  extracts 
causes  a  distinct  although  short-lasting  increase  in  the  blood- 
count.  It  is  stated  also  that  after  splenectomy  abnormal  amounts 
of  iron  are  excreted  and  that  there  is  a  diminution  in  the  quantity 
of  bile-pigments.  Asherf  believes  that  the  spleen  furnishes  a  sub- 
stance which  activates  the  processes  in  the  liver  concerned  with 
the  hemolysis  of  the  red  corpuscles  and  the  transformation  of  the 
hemoglobin.  The  most  definite  facts  known  about  the  spleen  are  in 
connection  with  its  movements.  It  has  been  shown  that  there  is  a 
slow  expansion  and  contraction  of  the  organ  synchronous  with  the 
digestion  periods.  After  a  meal  the  spleen  begins  to  increase  in  size, 
reaching  a  maximum  at  about  the  fifth  hour,  and  then  slowly  returns 
to  its  previous  size.  This  movement,  the  meaning  of  which  is  not 
known,  is  probably  due  to  a  slow  vasodilation,  together,  perhaps, 
with  a  relaxation  of  the  tonic  contraction  of  the  musculature  of  the 
trabeculse.  In  addition  to  this  slow  movement,  RoyJ  has  shown 
that  there  is  a  rhythmical  contraction  and  relaxation  of  the  organ, 
occurring  in  cats  and  dogs  at  intervals  of  about  one  minute.  Roy 
supposes  that  these  contractions  are  effected  through  the  intrinsic 
musculature  of  the  organ, — that  is,  the  plain  muscle  tissue  present 
in  the  capsule  and  trabeculse, — and  he  believes  that  the  contractions 
serve  to  keep  up  a  circulation  through  the  spleen  and  to  make  its 
vascular  supply  more  or  less  independent  of  variations  in  general 
arterial  pressure.  The  fact  that  there  is  a  special  local  arrangement 
for  maintaining  its  circulation  makes  the  spleen  unique  among  the 
organs  of  the  body,  but  no  light  is  thrown  upon  the  nature  of  the 
function  fulfilled.  The  spleen  is  supplied  richly  with  motor  nerve 
fibers  which  when  stimulated  either  directly  or  reflexly  cause  the 
organ  to  diminish  in  volume.  According  to  Schaefer,§  these  fibers 
are  contained  in  the  splanchnic  nerves,  which  carry  also  inhibitory 
fibers  whose  stimulation  produces  a  dilatation  of  the  spleen. 

The  chemical  composition  of  the  spleen  is  complicated,  but  sug- 
gestive. Its  mineral  constituents  are  characterized  by  a  large 
percentage  of  iron,  which  seems  to  be  present  as  an  organic  compound 
of  some  kind.  Analysis  shows  also  the  presence  of  a  number  of  fatty 
acids,  fats,  cholesterin,  and,  what  is  perhaps  more  noteworthy,  a, 
number  of  nitrogenous  extractives  belonging  to  the  group  of  purin 

*  Consult  Musser  and  Krumbhaar,  "Journal  of  Exp.  Medicine,"  18,  487, 
1913,  and  20,  108,  1914;  also  Pearce  and  Pepper,  ibid.,  20,  19,  1914. 
t  Ebnother,  "Biochemische  Zeitschrift,"  72,  416,  1916. 
j"  Journal  of  Physiology,"  3,  203,  1881. 
§  Ibid.,  20,  1,  1896. 


838  PHYSIOLOGY    OF    DIGESTION    AND   SECRETION. 

bases,  such  as  xanthin,  hypoxanthin,  adenin,  guanin,  and  uric  acid. 
The  presence  of  these  bodies  seems  to  indicate  that  active  metabolic 
changes  of  some  kind  occur  in  the  spleen.  As  to  the  theories  of  the 
splenic  functions,  the  following  may  be  mentioned:  (1)  The  spleen 
has  been  supposed  to  give  rise  to  new  red  corpuscles.  This  it  un- 
doubtedly does  during  fetal  life  and  shortly  after  birth,  and  in  some 
animals  throughout  life,  but  there  is  no  reliable  evidence  that  the 
function  is  retained  in  adult  life  in  man  or  in  most  of  the  mammals. 
The  presence  of  a  large  amount  of  iron  in  organic  combination 
suggests,  however,  that  the  spleen  may  play  a  part  in  the  prepara- 
tion of  new  hemoglobin,  or  in  the  preservation  of  the  iron  set  free 
by  the  death  of  the  red  corpuscles.  This  suggestion  is  strengthened 
by  the  fact  that  after  extirpation  of  the  spleen  there  is  a  distinct 
increase  in  the  daily  loss  of  iron  from  the  body,  in  dogs  an  increase 
from  11  to  18  or  29  mgm.*  (2)  It  has  been  supposed  to  be  an 
organ  for  the  destruction  of  red  corpuscles.  This  view  is  founded 
chiefly  on  microscopical  evidence,  according  to  which  certain 
large  ameboid  cells  in  the  spleen  ingest  and  destroy  the  old  red 
corpuscles,  and  partly  upon  the  fact  that  the  spleen  tissue  seems  to 
be  rich  in  an  iron-containing  compound.  (3)  It  has  been  sug- 
gested that  the  spleen  is  concerned  in  the  production  of  uric  acid. 
This  substance  is  found  in  the  spleen,  as  stated  above,  and  it  was 
shown  by  Horbaczewsky  that  the  spleen  contains  substances  from 
which  uric  acid  or  xanthin  may  readily  be  formed  by  the  action  of 
the  spleen-tissue  itself.  Later  investigations  f  have  shown  that 
the  spleen,  like  the  liver  and  some  other  organs,  contains  special 
enzymes  (adenase,  guanase,  and  xanthin  oxydase),  by  whose  action 
the  split  products  of  the  nucleins  may  be  converted  to  xanthin  or 
hypoxanthin,  and  it  is  possible,  therefore,  that  these  substances 
may  be  formed  in  the  spleen. 

*  Grossenbacher  and  Asher,  "Zentralblatt  f.  Physiol./'  No.  12,  1908. 
t  Consult  Jones  and  Austrian,  "Zeitschrift  f.  physiol.  Chem.  "  48,  110, 
1906. 


CHAPTER  XLV. 


THE  KIDNEY  AND  SKIN  AS  EXCRETORY  ORGANS. 

Structure  of  the  Kidney. — The  kidney  is  a  compound  tubular 
gland.  The  uriniferous  tubules  composing  it  may  be  roughly 
separated  into  a  secreting  part  comprising  the  capsule,  convoluted 
tubes,  and  loop  of  Henle,  and  a  collecting  part,  the  so-called  straight 
or  collecting  tube,  the  epithelium  of  which  is  assumed  not  to 
have  any  secretory  function.  Within  the  secreting  part  the  epithe- 
lium differs  greatly  in  character  in  different  regions;  its  peculiarities 
may  be  referred  to  briefly  here  so  far  as  they  seem  to  have  a  physio- 

E 


Fig.  298. — Portions  of  the  various  divisions  of  the  uriniferous  tubules  drawn  from 
sections  of  human  kidney:  A,  Malpighian  body;  x,  squamous  epithelium  lining  the  cap- 
sule and  reflected  over  the  glomerulus;  y,  z,  afferent  and  efferent  vessels  of  the  tuft;  et 
nuclei  of  capillaries;  n,  constricted  neck  marking  passage  of  capsule  into  convoluted  tu- 


bule;  B,  proximal  convoluted  tubule;    C,  irregular  tubule;   D  and  F,  spiral  tubules;   Et 
ascending  limb  of  Henle's  loop;   <?,  straight  collecting  tubule. — (Piersol.) 

logical  bearing,  although  for  a  complete  description  reference  must 
be  made  to  works  on  histology. 

The  arrangement  of  the  glandular  epithelium  in  the  capsule  with 
reference  to  the  blood-vessels  of  the  glomerulus  is  worthy  of  special 
attention.  It  will  be  remembered  that  each  Malpighian  corpuscle  con- 
sists of  two  principal  parts,  a  tuft  of  blood-vessels,  the  glomerulus,  and 
an  enveloping  expansion  of  the  uriniferous  tubule,  the  capsule.  The 
glomerulus  is  an  interesting  structure  (see  Fig.  298,  A).  It  consists 
of  a  small  afferent  artery  which  after  entering  the  glomerulus,  breaks 
up  into  a  number  of  capillaries.  These  capillaries,  although  twisted 

839 


840  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

together,  do  not  anastomose,  and  they  unite  to  form  a  single  efferent 
vein  of  a  smaller  diameter  than  the  afferent  artery.  The  whole 
structure,  therefore,  is  not  an  ordinary  capillary  area,  but  a  rete 
mirabile,  and  the  physical  factors  are  such  that  within  the  capil- 
laries of  the  rete  there  must  be  a  greatly  diminished  velocity  of  tha 
blood-stream,  owing  to  the  great  increase  in  the  width  of  the  stream 
bed,  and  a  higher  blood-pressure  than  in  ordinary  capillaries, 
owing  to  the  narrow  efferent  vessel  and  the  capillaries  of  the  tubule 
which  form  a  resistance  beyond  the  rete.  Surrounding  this 
glomerulus  is  the  double-walled  capsule.  One  wall  of  the  cap- 
sule is  closely  adherent  to  the  capillaries  of  the  glomerulus;  it 
not  only  covers  the  structure  closely,  but  dips  into  the  interior 
between  the  small  lobules  into  which  the  glomerulus  is  divided. 
This  layer  of  the  capsule  is  composed  of  flattened,  endothelial- 
like  cells,  the  glomerular  epithelium,  to  which  great  importance 
is  attached  in  the  formation  of  the  secretion.  It  will  be  no- 
ticed that  between  the  interior  of  the  blood-vessels  of  the  glomerulus 
and  the  cavity  of  the  capsule,  which  is  the  beginning  of  the  urin- 
iferous  tubule,  there  are  interposed  only  two  very  thin  layers, — 
namely,  the  epithelium  of  the  capillary  wall  and  the  glomerular 
epithelium.  The  apparatus  would  seem  to  afford  most  favorable 
conditions  for  filtration  of  the  liquid  parts  of  the  blood.  The  epi- 
thelium clothing  the  convoluted  portions  of  the  tubule,  including 
under  this  designation  the  so-called  irregular  and  spiral  portions 
and  the  loop  of  Henle,  is  of  a  character  quite  different  from  that  of 
the  glomerular  epithelium  (Fig.  298,  B,  C,  D,  E,  F,  G).  The  cells, 
speaking  generally,  are  cuboidal  or  cylindrical,  protoplasmic,  and 
granular  in  appearance;  on  the  side  toward  the  basement  mem- 
brane they  often  show  a  peculiar  striation,  while  on  the  lumen  side 
the  extreme  periphery  presents  a  compact  border  which  in  some 
cases  shows  a  cilia-like  striation.  These  cells  have  the  general 
appearance  of  an  active  secretory  epithelium,  and  one  theory  of 
urinary  secretion  attributes  this  function  to  them. 

The  Secretion  ,of  Urine. — The  kidneys  receive  a  rich  supply 
of  nerve  fibers,  but  most  histologists  have  been  unable  to  trace  any 
connection  between  these  fibers  and  the  epithelial  cells  of  the  kidney 
tubules. 

The  majority  of  purely  physiological  experiments  upon  direct 
stimulation  of  the  nerves  going  to  the  kidney  are  adverse  to  the 
theory  of  secretory  fibers,  the  marked  effects  obtained  in  these  ex- 
periments being  all  explicable  by  the  changes  produced  in  the  blood- 
flow  through  the  organ.  Two  general  theories  of  urinary  secretion 
have  been  proposed.  Ludwig  held  originally  that  the  urine  is 
formed  by  the  simple  physical  processes  of  filtration  and  diffusion. 
In  the  glomeruli  the  conditions  are  most  favorable  to  filtration,  and 
he  supposed  that  in  these  structures  water  filtered  through  from  the 


KIDNEY    AND    SKIN    AS    EXCRETORY    ORGANS.  841 

blood,  carrying  with  it  not  only  the  inorganic  salts,  but  also  the 
specific  elements  (urea,  etc.)  of  the  secretion.  There  was  thus 
formed  at  the  beginning  of  the  uriniferous  tubules  a  complete  but 
diluted  urine,  and  in  the  subsequent  passage  of  this  liquid  along  the 
convoluted  tubes  it  became  concentrated  by  diffusion  with  the  more 
concentrated  lymph  surrounding  the  outside  of  the  tubules. 

Bowman's  theory  of  urinary  secretion,  which  has  since  been 
vigorously  supported  and  extended  by  Heidenhain,  was  based  orig- 
inally mainly  on  histological  grounds.  It  assumes  that  in  the 
glomeruli  water  and  inorganic  salts  are  produced,  while  the  urea 
and  related  bodies  are  eliminated  through  the  activity  of  the  epi- 
thelial cells  in  the  convoluted  tubes. 

The  first  of  these  theories  (Ludwig)  is  sometimes  spoken  of  as 
the  mechanical  theory,  since  as  originally  proposed  it  attempted 
to  explain  the  formation  and  composition  of  the  urine  by  reference 
only  to  the  physical  forces  of  nitration  and  diffusion.*  Adherents 
of  this  view  in  recent  years  have  modified  it,  however,  to  the  extent 
that  the  absorption  supposed  to  take  place  in  the  convoluted  tub- 
ules is  designated  as  a  selective  absorption,  or  selective  diffusion,  the 
characteristics  of  which  depend  upon  unknown  peculiarities  of  struc- 
ture in  the  epithelial  cell,  so  that  it  is  no  longer  a  purely  mechanical 
theory.  The  difference  between  the  mechanical  and  the  secretory 
theories  may  be  stated  briefly  in  this  way.  The  former  assumes  that 
in  the  glomerulus  all  of  the  constituents  of  the  urine  are  produced 
from  the  blood,  probably  by  filtration,  and  that  the  function  of  the 
epithelium  lining  the  convoluted  tubules  is  absorptive,  like  the 
epithelium  of  the  intestines,  and  not  secretory.  The  Bowman  view 
as  formulated  by  Heidenhain  teaches  that  the  glomerular  epithe- 
lium forms  the  water  and  salts  of  the  urine  by  an  act  of  secretion, 
the  ultimate  chemistry  or  physics  of  which  is  not  known.  The 
theory  asserts  that  the  epithelial  cells  participate  actively  in  the 
process  of  secretion  and  do  not  serve  simply  as  a  passive  membrane. 
The  cells  of  the  convoluted  tubules  are  also  secretory,  their  special 
activity  being  limited  mainly  to  the  organic  constituents,  urea,  etc., 
although,  in  this  respect, — namely,  in  the  precise  distinction  be- 
tween the  secretory  products  of  the  glomerular  epithelium  and  those 
of  the  convoluted  tubules, — the  theory  is  not  very  explicit.  Much 
interest  and  a  large  literature  have  been  stimulated  by  controver- 
sies based  on  these  theories,  and  to-day  the  facts  accumulated  are 
not  such  as  to  demonstrate  conclusively  one  view  or  the  other, 
although,  on  the  whole,  perhaps,  it  may  be  said  that  the  majority  of 

*  Sir  Lauder  Brunton  calls  my  attention  to  the  fact  that  Ludwig,  in  some 
of  his  earlier  investigations  (Ustimowitsch,  Ludwig's  "Arbeiten,"  1870), 
recognized  the  fact  that  the  flow  of  urine  through  the  glomeruli  is  influenced 
by  factors  other  than  the  mechanical  pressure.  He  called  attention  especially 
to  the  influence  of  the  diuretic  substances  present  in  the  blood,  such  as  urea 
and  sodium  chlorid. 


842  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

physiologists  adhere  to  the  more  conservative  view  of  Bowman- 
Heidenhain  to  the  extent  at  least  of  recognizing  that  the  physical 
laws  of  nitration,  diffusion,  and  imbibition,  so  far  as  they  are  known, 
do  not  suffice  for  a  satisfactory  explanation  of  the  facts.*  As  in 
other  similar  cases,  our  knowledge  of  the  physical  structure  and 
chemical  properties  of  the  walls  of  the  living  cells  is  still  very  de- 
ficient, and  it  seems  necessary  to  designate  these  activities  by  the 
indefinite  term  secretion. 

Function  of  the  Glomerulus. — As  stated  above,  the  structure 
of  the  glomerulus  is  peculiar  and  suggestive  of  a  special  adaptation. 
The  mechanical  theory  looks  upon  it  as  a  filter,  the  pressure  of  the 
blood  in  the  glomerular  capillaries  driving  the  water  and  salts 
through  the  endothelium  of  the  capillaries  and  the  glomerular  epi- 
thelium into  the  cavity  of  the  urinary  tubule.  If  we  consider 
only  the  water  and  assume  that  the  membranes  traversed  are  freely 
permeable  to  its  molecules,  then  it  is  evident  that,  upon  this  theory, 
the  quantity  of  urine  formed  will  depend  upon  the  filtration  pres- 
sure, and  that  this  filtration  pressure  can  be  expressed  by  the  formula 
F=P — p,  in  which  P  represents  the  blood-pressure  in  the  glom- 
erular capillaries  and  p  the  pressure  of  the  urine  in  the  capsular 
end  of  the  uriniferous  tubules.  Some  of  the  interesting  facts  de- 
veloped by  experiment  may  be  presented  in  connection  with  this 
formula.  According  to  the  mechanical  theory,  the  amount  of  urine 
formed  should  vary  directly  with  P  and  inversely  with  p.  The 
factor  P  may  be  increased  in  two  general  ways:  First,  by  those 
changes  which  raise  general  arterial  pressure  and  therefore  the 
pressure  in  the  renal  arteries, — such  changes,  for  instance,  as  are 
brought  about  by  an  increased  force  of  heart  beat  or  a  large  vaso- 
constriction.  Second,  by  obstructing  or  occluding  the  renal  veins. 
Experiments  have  been  made  along  these  lines.  With  regard  to 
the  first  possibility  it  has  been  found  in  general,  although  not  invar- 
iably, that  raising  arterial  pressure  increases  the  quantity  of  urine 
if  the  means  used  are  such  as  may  be  assumed  to  raise  the  pressure 
in  the  glomerular  capillaries. 

The  reverse  experiment,  however,  of  raising  P  by  blocking  the 
venous  outflow  fails  entirely  to  support  the  theory.  When  the  renal 
veins  are  compressed  the  capillary  pressure  in  the  glomeruli  must 
be  increased,  and,  if  the  veins  are  blocked  entirely,  we  may  suppose 
that  the  capillary  pressure  is  raised  to  the  level  of  that  of  the  renal 
arteries.  In  such  experiments,  however,  the  flow  of  urine  is  di- 
minished instead  of  being  increased,  and  indeed  may  be  stopped 
altogether  when  the  veins  are  completely  blocked.  The  adherents  of 
the  mechanical  theory  have  attempted  to  explain  this  unfavorable 
result  by  assuming  that  the  swollen  interlobular  veins  press  upon 

*  For  discussion  and  literature  see  Magnus,  "Miinchener  med.  Wochen- 
schrift,"  1906,  Nos.  28  and  29. 


KIDNEY    AND    SKIN   AS    EXCRETORY    ORGANS.  843 

and  block  the  uriniferous  tubules.     According  to  the  antagonistic 
theory  of  Heidenhain,  blocking  the  veins  suppresses  the  secretory 
activity  of  the  glomerular  epithelium  by  depriving  it  of  oxygen  and 
the  chance  for  removal  of  CO2, — that  is,  by  producing  local  as- 
phyxia.    The  latter  explanation  seems  the  simpler  of  the  two,  and  it 
is  very  strongly  supported  by  the  opposite  experiment  of  clamping 
the  renal  artery.     When  this  is  done  the  blood-flow  through  the 
kidney  ceases  and  the  secretion  of  urine  also  stops,  as  would  be 
expected.    But  when  after  a  few  minutes'  closure  the  artery  is  un- 
damped, the  secretion  is  not  restored  with  the  return  of  the  cir- 
culation.    On  the  contrary,  a  long  time  (as  much  as  an  hour  or  more) 
may  elapse  before  the  secretion  begins.    This  fact  is  quite  in  harmony 
with  the  Heidenhain  theory,  since  complete  removal  of  their  blood 
supply  might  well  result  in  a  long-continued  injury  to  the  delicate 
epithelial  cells.     On  the  mechanical  theory,  however,  we  should 
expect  a  contrary  result.     Injury  to  the  cells  should  be  followed  by 
greater  permeability  and  an  increased  filtration,  as  is  found  to  be 
the  case  with  the  production  of  lymph.     These  two  experiments, 
blocking  the  renal  artery  and  the  renal  vein,  seem  at  present  to  dis- 
credit the  filtration  theory  and  to  support  the  secretion  theory. 
If  we  accept  this  latter  theory  it  may  be  asked  how  it  agrees  with 
the  experiments  mentioned  above  upon  the  variations  in  capillary 
pressure  brought  about  otherwise  than  by  obstructing  the  venous 
outflow.     Heidenhain  has  emphasized  the  fact  that  all  of  these  ex- 
periments involve  not  only  a  variation  in  capillary  pressure,  but  also 
in  the  blood-flow,  and  that  it  is  open  to  us  to  suppose  that  the 
effect  upon  the  secretion  of  urine  is  dependent  upon  the  rate  of  flow 
rather  than  upon  the  capillary  pressure.     If  we  adopt  this  expla- 
nation we  are  led  again  to  the  secretion  hypothesis.     Mere  rate  of 
flow  should  not  influence  filtration,  but  might  affect  secretion,  since 
it  would  alter  the  volume  of  blood  which  passed  by  the  cells  in  a 
given  time  and  thereby  would  vary  the  quantity  of  gxygen  sup- 
plied and  of  carbon  dioxid  removed,  and  also  the  quantity  of  chem- 
ical substances  in  the  blood  which  may  act  as  chemical  stimuli  to 
the  cells.     An  important  fact,  which  seems  at  first  sight  to  show  a 
direct  influence  of  pressure,  is  that  when  general  arterial  pressure 
falls  below  a  certain  point,  about  40  mm.  of  mercury,  the  secretion 
of  urine  ceases  altogether.     Such  a  condition  may  be  brought  about 
by  surgical  shock,  by  hemorrhage,  or  by  section  of  the  spinal  cord  in 
the  cervical  or  thoracic  region.     But  here  again  the  great  vascular 
dilation  causing  this  fall  of  pressure  is  associated  with  a  feeble  cir- 
culation, and  the  effect  upon  the  kidney  secretion  may  well  be  due 
to  this  latter  factor. 

In  addition  to  varying  the  factor  P  in  the  formula  given  above, 
it  is  possible  also  to  increase  the  factor  p.    Normally,  the  pressure 


844  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

of  the  urine  in  the  capsule  must  be  very  low,  owing  to  the  fact  that 
the  secretion  drains  away  as  rapidly  as  it  is  formed.  If  the  ureter 
is  occluded,  however,  the  pressure  of  the  urine  will  increase,  and  the 
filtration  pressure  P — p  will  diminish.  When  this  experiment  is 
performed  and  the  pressure  in  the  ureter  is  measured  by  a  manom- 
eter, it  is  found  to  rise  to  50  or  60  mms.  of  mercury  and  then  to 
remain  stationary.  This  fact  might  be  explained  by  supposing 
that  when  p  =  P  the  secretion  stops  on  account  of  the  failure  of 
the  filtration  pressure.  Little  weight,  however,  can  be  given  to 
this  argument,  since  it  is  quite  possible  that  under  these  condi- 
tions the  urine  may  still  continue  to  form,  but  be  reabsorbed  under 
the  high  tension  reached.  The  experiment  simply  serves  to  show 
the  secretion  pressure  of  the  urine,  and  the  fact  that  this  pressure 
rises  as  high  as  50  to  60  mms.  mercury,  while  the  capillary  pressure 
is  probably  somewhat  lower,  would  rather  serve  as  an  argument 
against  the  filtration  theory.  Moreover,  experiments  show  *  that 
when  a  certain  moderate  resistance  is  established  in  the  ureters 
(p  =  10  cms.  H2O)  the  flow  of  urine  is  actually  increased,  a  fact 
entirely  opposed  to  the  mechanical  theory. 

Function  of  the  Convoluted  Tubule. — By  the  term  convoluted 
tubule  is  meant  here  the  entire  stretch  from  the  glomerulus  to  the 
straight  tubules.  Its  epithelium  varies  in  character;  its  cells  are 
distinguished  in  general,  as  contrasted  with  the  glomerular  epithe- 
lium, by  a  relatively  large  amount  of  granular  protoplasm.  The 
question  of  interest  at  present  in  regard  to  this  epithelium  is  whether 
it  is  secretory  or  absorptive.  The  original  view  of  Ludwig  that 
diffusion  takes  place  in  these  tubules  between  the  urine  and  the 
blood  (lymph)  in  accordance  with  simple  physical  laws  and  that 
by  this  action  alone  the  dilute  urine  is  brought  to  its  normal  concen- 
tration must  be  abandoned.  The  mere  fact  that  the  urine  may  be 
more  concentrated  in  certain  constituents  than  the  blood  is  suffi- 
cient evidence  that  other  factors  must  co-operate.  Those  who  be- 
lieve that  the  main  function  of  the  tubules  is  absorptive  are  obliged 
to  regard  this  process  as  physiological,  as  a  selective  absorption 
depending  upon  the  living  structure  and  properties  of  the  epithelial 
cells.  The  kind  of  evidence  upon  which  this  view  is  based  is  some- 
what indirect;  a  single  example  may  suffice.  Cushny  statesf  that 
if  certain  diuretics — for  example,  sodium  chlorid  and  sodium  sul- 
phate— are  injected  simultaneously  into  the  blood  and  in  such 
amounts  that  an  equal  number  of  anions  (Cl  and  SO4)  is  pres- 
ent, the  quantities  that  are  excreted  in  the  urine  during  the  next 
hour  or  two  follow  different  curves  and  vary  independently  of  their 
concentration  in  the  plasma.  While  this  independence  might  be 

*  Brodie  and  Cullis,  "  Journal  of  Physiology,"  1906,  xxxiv.,  224. 
t  "Journal  of  Physiology,"  27,  429,  1902. 


KIDNEY    AND    SKIN    AS    EXCRETORY    ORGANS.  845 

referred  to  a  specific  secretory  action,  the  author  finds  a  simpler 
explanation  in  variations  in  absorption,  the  epithelium  of  the  con- 
voluted tubule,  like  that  of  the  intestine,  absorbing  the  sulphate 
with  more  difficulty.  On  the  other  side,  the  facts  that  have  been 
urged  in  favor  of  the  secretory  hypothesis  are  more  numerous  and 
varied.  Some  of  these  facts  are  as  follows:  (1)  It  is  stated  that 
if  the  ureters  are  ligated  in  birds  the  urates  will  be  found  deposited 
in  the  uriniferous  tubules,  but  never  at  the  capsular  end.  (2) 
Heidenhain  has  given  proof 'that  the  convoluted  tubules  are  capa- 
ble of  excreting  indigo-carmin  after  this  substance  is  injected  into 
the  blood.  His  experiment  consisted  in  injecting  the  material  into 
the  blood,  after  dividing  the  cord  so  as  to  reduce  the  rapidity  of 
secretion.  After  a  certain  interval  the  kidney  was  removed  and 
irrigated  with  alcohol  to  precipitate  the  indigo-carmin  in  situ  in 
the  organ.  Microscopical  examination  showed  that  after  this 
treatment  the  granules  of  the  indigo-carmin  are  found  in  the  con- 
voluted tubules,  but  not  in  the  capsules  around  the  glomeruli. 

(3)  Microchemical  staining  reactions  have  been  used  by  several 
observers  to  show  that  salts  foreign  to  the  blood,  such  as  the 
iodids  and  ferrocyanids,  are    excreted  through  the  convoluted 
tubules  and  not  through  the  glomerulus.    Recently  Leschke  *  has 
demonstrated  by  similar  staining  reactions  that  urea,  uric  acid, 
sodium  chlorid,  and  sodium  phosphate  are  all  eliminated  through 
the  epithelium  of  the  convoluted  tubules.     Each  of  these  sub- 
stances, when  introduced  into  the  blood,  could  be  detected  in 
concentrated  form  in  the  cells  of  the  convoluted  tubules,  while 
no  evidence  of  their  presence  in  the  glomeruli  could  be  obtained. 

(4)  Several  observers  (Van  der  Stricht,  Disse,  Trambasti,  Gur- 
witschf)  have  described  microscopical  appearances  in  the  cells 
lining  the  tubules  indicative  of  an  active  secretion.     They  picture 
the  formation  of  vesicles  in  the  cells  and  appearances  which  indi- 
cate the  discharge  of  these  vesicles  into  the  cavity  of  the  tubules. 

(5)  Nussbaum  made  use  of  the  fact  that  in  the  frog  the  glomeruli 
are  supplied  by  branches  of  the  renal  artery,  while  the  rest  of  the 
tubes  are  supplied  by  the  renal  portal  vein.     He  stated  that  if  the 
renal  artery  is  ligated  the  glomeruli  are  deprived  completely  of 
blood,  and  that  as  a  result  the  flow  of  urine  ceases.     If  under 
these  conditions  urea  is  injected  into  the  circulation,  it  is  excreted 
together  with  some  water,  thus  proving  the  secretory  activity  of 
the  tubules  with  regard  to  urea.     These  results,  although  denied 
at   one  time,   have  later  been  confirmed    and  extended.!     (6) 

*  Leschke,  "Zeitschrift  fiir  klinische  Medizin,"  81,  14,  1914. 
t  See  Gurwitsch,  "Archiv  f.  die  gesammte  Physiologic,"  19,  71,  1902. 
j  Bainbridge  and  Beddard,  " Journal  of  Physiology,"  1906,  xxxiv.  (Proc. 
Physiol.  Soc.);  also  Cullis,  ibid.,  p.  250. 


846  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

Dreser  has  shown  that  the  acidity  of  the  urine  is  due  to  an  action 
of  the  epithelium  of  the  tubules.  If  an  acid  indicator,  such  as 
acid  fuchsin,  is  injected  into  the  dorsal  lymph-sac  of  a  frog,  and  an 
hour  or  so  later  the  kidneys  are  examined,  it  will  be  found  that  the 
convoluted  tubules  are  colored  red,  while  the  capsular  end  is 
colorless,  indicating  that  the  secretion  at  the  latter  point  has  an 
alkaline  reaction.  The  experiment  shows  that  the  acid  substances 
in  the  urine  are  produced  in  the  convoluted  tubules.  The  sim- 
plest explanation  is  that  they  are  formed  by  a  secretory  activity 
of  the  epithelial  cells.  (7)  Studies  of  the  gaseous  exchanges  in  the 
kidney  during  diuresis*  and  during  the  glycosuria  caused  by 
phlorhizin  f  tend  to  support  the  secretion  hypothesis  to  the  extent 
that  they  prove  an  increased  metabolism  during  functional 
activity.  (8)  The  action  of  diuretics  (see  below).  On  the  whole, 
it  must  be  admitted  that  the  weight  of  evidence  is  in  favor  of 
the  Bowman-Heidenhain  theory  of  secretion. 

Action  of  Diuretics. — An  important  side  of  the  theories  of 
secretion  of  urine  is  their  application  to  the  action  of  diuretics. 
Water;  various  soluble  substances,  such  as  salts,  urea,  and  dextrose; 
and  certain  special  drugs,  such  as  caffein  or  digitalis,  exert  a  diuretic 
action  on  the  kidneys.  Much  experimental  work  has  been  done 
to  ascertain  whether  the  action  of  these  substances  can  be  explained 
mechanically  by  their  influence  on  the  blood-flow  or  the  blood- 
pressure  in  the  kidney  capillaries,  or  whether  it  is  necessary  to  fall 
back  upon  a  specific  stimulating  effect  exerted  by  them,  upon  the 
epithelial  cells  of  the  tubules.  Adherents  of  the  original  Ludwig 
theory  are  forced  to  explain  their  action  by  the  effect  they  pro- 
duce upon  the  pressure  in  the  kidney  capillaries,  and,  indeed,  it 
has  been  shown  with  reference  to  the  saline  diuretics  that  their 
effect  upon  the  secretion  is  in  proportion  to  the  osmotic  pressure 
they  exert.  It  has  been  suggested,  therefore,  that  the  action  of 
these  diuretics  lies  in  the  fact  that  they  attract  water  from  the  tis- 
tues  into  the  blood  and  thus  cause  a  condition  of  hydremic  plethora. 
But  whether  the  elimination  of  this  excess  of  water  is  due  to  filtra- 
tion or  to  an  active  secretion  by  the  glomerular  epithelium  is  a 
question  that  revives  the  discussion  that  has  been  presented  briefly 
above.  Most  observers  find  that  the  vascular  changes  in  the  kid- 
ney, particularly  after  the  administration  of  caffein  and  digitalis, 
do  not  explain  satisfactorily  the  phenomenon  of  diuresis.  It  has 
been  shown  also  that  some  diuretics  cause  an  increased  flow  of 
urine  without  affecting  the  amount  of  oxygen  absorbed  from  the 
blood  by  the  kidney.  Others,  however,  cause  a  distinct  increase 
in  the  oxygen  consumption.  Since  the  oxygen  consumption  may 

*  Barcroft  and  Brodie,  "Journal  of  Physiology,"  33,  52,  1906. 
t  Pavy,  Brodie,  and  Siam,  ibid.,  29,  467,  1903. 


KIDNEY    AND    SKIN    AS    EXCRETORY    ORGANS.  847 

be  considered  as  an  indication  of  cellular  activity,  this  result  would 
tend  to  show  that  some  diuretics  may  cause  a  genuine  secretion, 
while  others  influence  the  amount  of  urine  through  mechanical  or 
physical  influences  alone.*  In  the  case  of  the  inorganic  salts  it 
may  be  said  (Magnus)  that  there  is  for  each  salt  a  "secretion  thresh- 
old." An  increase  in  concentration  above  this  level  leads  to  the 
elimination  of  the  excess  of  salt  and  an  increased  secretion  of  water. 

The  Blood-flow  through  the  Kidneys. — It  will  be  inferred 
from  the  discussion  above  that,  other  conditions  remaining  the  same, 
the  secretion  of  the  kidney  varies  with  the  quantity  of  blood  flowing 
^hrough  it.  It  is,  therefore,  important  to  refer  briefly  to  the  nature 
and  especially  the  regulation  of  the  blood-flow  through  this  organ, 
although  the  same  subject  is  referred  to  in  connection  with  the 
general  description  of  vasomotor  regulation  (see  Grculation).  It 
has  been  shown  by  Landergren  t  and  Tigerstedt  that  the  kidney 
is  a  very  vascular  organ,  at  least  when  it  is  in  strong  functional  activ- 
ity such  as  may  be  produced  by  the  action  of  diuretics.  They  esti- 
mate that  in  a  minute's  time,  under  the  action  of  diuretics,  an  amount 
of  blood  flows  through  the  kidney  equal  to  the  weight  of  the  organ; 
this  is  an  amount  from  four  to  nineteen  times  as  great  as  occurs  in 
the  average  supply  of  the  other  organs  in  the  systemic  circulation. 
Taking  both  kidneys  into  account,  their  figures  show  that  (in  strong 
diuresis)  5.6  per  cent,  of  the  total  quantity  of  blood  sent  out  of  the 
left  heart  in  a  minute  may  pass  through  the  kidneys,  although  the 
combined  weight  of  these  organs  makes  only  0.56  per  cent,  of  that 
of  the  body  (see  table  p.  487). 

The  nature  of  the  supply  of  vasomotor  nerves  to  the  kidney  and 
the  conditions  which  bring  them  into  activity  are  fairly  well  known, 
owing  to  the  useful  invention  of  the  oncometer  by  Roy.  This  in- 
strument is,  in  principle,  a  plethysmograph  especially  modified 
for  use  upon  the  kidney  of  the  living  animal.  It  is  a  kidney-shaped 
box  of  thin  brass  made  in  two  parts,  hinged  at  the  back,  and  with 
a  clasp  in  front  to  hold  them  together.  In  the  interior  of  the  box 
thin  peritoneal  membrane  is  so  fastened  to  each  half  that  a  layer 
of  olive  oil  may  be  placed  between  it  and  the  brass  walls.  There 
is  thus  formed  in  each  half  a  soft  pad  of  oil  upon  which  the  kidney 
rests.  When  the  kidney,  freed  as  far  as  possible  from  fat  and  sur- 
rounding connective  tissue,  but  with  the  blood-vessels  and  nerves 
entering  at  the  hilus  entirely  uninjured,  is  laid  in  one-half  of  the  on- 
cometer, and  the  other  half  is  shut  down  upon  it  and  tightly  fas- 
tened, the  organ  is  surrounded  by  oil  in  a  box  which  is  liquid-tight 
at  every  point  except  one,  from  which  a  tube  is  led  off  to  some  suitable 
recorder  such  as  a  tambour.  Under  these  conditions  every  increase 

*  Barcroft  and  Straub,  ibid.,  1910,  xli.,  213. 

t  "Skandinavisches  Archiv  f.  Physiologic,"  4,  241,  1892. 


848  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

in  the  volume  of  the  kidney  causes  a  proportional  outflow  of  oil 
from  the  oncometer,  which  is  measured  by  the  recorder,  and 
every  diminution  in  volume  is  accompanied  by  a  reverse  change. 
At  the  same  time  the  flow  of  urine  during  these  changes  can  be 
determined  by  inserting  a  cannula  into  the  ureter  and  measuring 
directly  the  outflow  of  urine.  By  this  and  other  means  it  has 
been  shown  that  the  kidney  receives  a  rich  supply  of  vasoconstrictor 
nerve  fibers  that  reach  it  between  and  around  the  entering  blood- 
vessels. These  fibers  emerge  from  the  spinal  cord  chiefly  in  the 
lower  thoracic  spinal  nerves  (tenth  to  thirteenth  in  the  dog) ,  pass 
through  the  sympathetic  system,  and  reach  the  organ  as  postgan- 
glionic  fibers.  Stimulation  of  these  nerves  causes  a  contraction  of 
the  small  arteries  of  the  kidney,  a  shrinkage  in  volume  of  the  whole 
organ  as  measured  by  the  oncometer  (see  Fig.  240) ,  and  a  dimin- 
ished secretion  of  urine.  When,  on  the  other  hand,  these  con- 
strictor fibers  are  cut  as  they  enter  the  hilus  of  the  kidney,  the  ar- 
teries are  dilated  on  account  of  the  removal  of  the  tonic  action  of 
the  constrictor  fibers,  the  organ  enlarges,  and  a  greater  quantity 
of  blood  passes  through  it,  since  the  resistance  to  the  blood-flow  is 
diminished  while  the  general  arterial  pressure  in  the  aorta  remains 
practically  the  same.  Along  with  this  greater  flow  of  blood  there 
is  a  marked  increase  in  the  secretion  of  urine. 

Under  normal  conditions  we  must  suppose  that  these  fibers  are 
brought  into  play  to  a  greater  or  less  extent  by  reflex  stimulation, 
and  thus  serve  to  control  the  blood-flow  through  the  kidney  and 
thereby  influence  its  functional  activity.  It  has  been  shown,  too, 
that  the  kidney  receives  vasodilator  nerve-fibers, — that  is,  fibers 
which  when  stimulated  directly  or  reflexly  cause  a  dilatation  of 
the  arteries,  and  therefore  a  greater  flow  of  blood  through  the  or- 
gan. According  to  Bradford,  these  fibers  emerge  from  the  spinal 
cord  mainly  in  the  anterior  roots  of  the  eleventh,  twelfth,  and  thir- 
teenth thoracic  spinal  nerves.  Under  normal  conditions  these  fibers 
are  probably  thrown  into  action  by  reflex  stimulation  and  lead  to 
an  increased  functional  activity.  It  will  be  seen,  therefore,  that  the 
kidneys  possess  a  local  nervous  mechanism  through  which  their 
secretory  activity  may  be  increased  or  diminished  by  correspond- 
ing alterations  in  the  blood-supply.  So  far  as  is  known,  this  is  the 
only  way  in  which  the  secretion  in  the  kidneys  can  be  directly  af- 
fected by  the  central  nervous  system.  It  should  be  borne  in  mind, 
also,  that  the  blood-flow  through  the  kidneys,  and  therefore  their 
secretory  activity,  may  be  affected  by  conditions  influencing  general 
arterial  pressure.  Conditions  such  as  asphyxia,  strychnin  poison- 
ing, or  painful  stimulation  of  sensory  nerves,  which  cause  a  general 
vasoconstriction,  influence  the  kidney  in  the  same  way,  and  tend, 
therefore,  to  diminish  the  flow  of  blood  through  it;  while  conditions 


KIDNEY     iND    SKIN    AS    EXCRETORY    ORGANS.  849 

which  lower  general  arterial  pressure,  such  as  general  vascular  dila- 
tation of  the  skin  vessels,  may  also  depress  the  secretory  action  of 
the  kidney  by  diminishing  the  amount  of  blood  flowing  through  it. 

In  what  way  any  given  change  in  the  vascular  conditions  of  the 
body  will  influence  the  secretion  of  the  kidney  depends  upon  a  num- 
ber of  factors  and  their  relations  to  one  another,  but  any  change 
which  will  increase  the  difference  in  pressure  between  the  blood  in 
the  renal  artery  and  the  renal  vein  will  tend  to  augment  the  flow 
of  blood  unless  it  is  antagonized  by  a  simultaneous  constriction  in 
the  small  arteries  of  the  kidney  itself.  On  the  contrary,  any  vas- 
cular dilatation  of  the  vessels  in  the  kidney  will  tend  to  increase 
the  blood-flow  through  it  unless  there  is  at  the  same  time  such  a 
general  fall  of  blood-pressure  as  is  sufficient  to  lower  the  pressure 
in  the  renal  artery  and  reduce  the  driving  force  of  the  blood  to  an 
extent  that  more  than  counteracts  the  favorable  influence  of  dimin- 
ished resistance  in  its  small  arteries. 

Hormone  Stimulation. — The  evidence  for  the  existence  of 
secretory  nerves  to  the  kidney  is  either  negative  or  unsatisfactory. 
The  secretion  of  urine  is  probably  controlled  through  chemical 
stimuli.  Various  foreign  substances,  or  the  normal  constituents  of 
the  blood  when  in  excess  of  a  certain  concentration,  are  secreted, 
presumably,  on  the  general  theory  adopted,  because  they  stimulate 
in  some  way  the  activity  of  the  kidney  cells. 

The  increased  amount  of  urine  that  occurs  when  the  blood- 
flow  through  the  gland  is  increased  may  be  referred  in  a  general 
way  to  the  greater  amount  of  these  chemical  stimuli,  excretory 
products,  etc.,  that  pass  through  the  organ.  The  general  metabo- 
lism of  the  body  is  constantly  adding  to  the  blood  substances  of 
this  kind,  which  manifest  some  special  reaction  with  the  kidney 
cells  that  results  in  their  secretion.  But,  in  addition  to  these 
general  stimuli,  it  is  possible  that  specific  hormones  may  be  pro- 
duced that  are  adapted  to  stimulate  the  kidneys  and  correlate 
their  activity  to  conditions  elsewhere  in  the  body.  Schaefer* 
and  Herring  have  shown  that  a  substance  is  contained  in  extracts 
of  the  posterior  lobe  of  the  pituitary  gland  which  has  this  action, 
and  it  is  quite  probable  that  this  hormone  may  function  normally, 
although  as  yet  we  know  nothing  of  the  conditions  under  which  it 
acts.  Cowf  has  stated  that  a  similar  diuretic  hormone  is  formed 
in  the  mucous  membrane  of  the  intestine,  particularly  of  the  duo- 
denum and  jejunum.  When  water  is  taken  this  hormone  is  carried 
into  the  blood  with  the  absorbed  water  and  is  responsible  for  the 
resulting  diuresis.  It  is  stated  that  water  taken  by  mouth  causes 

*  Schaefer  and  Herring,  "Philosophical  Transactions"  (London),  B.  199,  1, 
1906. 

t  Cow,  "Journal  of  Physiology,"  48,  1,  1914. 

54 


850 


PHYSIOLOGY    OF    DIGESTION   AND    SECRETION. 


diuresis,  when  a  similar  amount  injected  directly  into  the  blood 
may  have  no  effect.  These  suggestive  experimental  facts  indicate 
the  possibility  that  the  secretion  of  the  kidney  may  be  controlled 
in  a  more  specific  way  than  has  been  supposed  heretofore. 

The  Composition  of  Urine. — The  urine  of  man  is  a  yellowish 
liquid  that  varies  greatly  in  depth  of  color.  It  has  an  average 
specific  gravity  of  1.020  and  usually  an  acid  reaction  to  litmus 
paper.  This  acid  reaction  is  attributed  generally  to  the  presence 
of  acid  phosphates,  particularly  acid  sodium  phosphate  (NaH2PC>4), 
but,  according  to  Folin,  it  is  due  partially  tb  organic  acids.  As 
determined  by  physicochemical  methods,  normal  human  urine 
shows  on  the  average  a  true  acidity  equivalent  to  a  concentration 
of  hydrogen  ions  of  10~6  or  0.000001  grams  per  liter.  In  place  of  the 
actual  concentration  of  the  hydrogen  ions  it  is  customary  to  use  the 
logarithm  of  the  figure  expressing  the  concentration.  These  logar- 
ithms are  all  negative,  but  are  written  without  the  minus  sign  as 
the  hydrogen  exponent.  Thus: 

HYDROGEN  ION  CONCENTRATION.  HYDROGEN  EXPONENT. 

1  X  KH  or  0.1 1 

2  X  1(H  or  0.002 2.7  (+  0.3  —3) 

5  X  10-8  or  0.000005 5.3  (+  0.7  —6) 

In  this  nomenclature  the  acidity  of  the  urine  varies  between  limits, 

+ 

expressed  by  the  figures  4.82  and  7.45  (H  concentrations,  0.000016 
and  0.00000008).*  In  comparison  with  these  figures  it  may  be 
recalled  that  a  neutral  reaction,  such  as  is  shown  by  water,  is 

expressed  by  the  exponent  7,  while  blood  inclines  to  the  alkaline 

+ 

side,  exponent  of  7.4  (H  concentration,  0.4  X  10~7).  One  of  the 
conditions  influencing  the  reaction  of  the  urine  is  the  character 
of  the  food.  On  an  animal  diet  the  acidity  is  increased;  on  a 
vegetable  diet  it  is  diminished  and  may  reach  the  neutral  point 
or  the  degree  of  alkalinity  exhibited  by  the  blood.  In  the  latter 
case  the  urine  may  give  a  blue  reaction  to  litmus  paper,  owing  to 
the  alkaline  salts  present,  but,  as  has  been  explained  (p.  416),  this 
reaction  does  not  demonstrate  a  true  alkalinity,  that  is,  an  excess  of 
— OH  ions  over  the  +H  ions.  Distinct  alkalinity  in  this  sense 
may  be  shown  when  the  urine  has  undergone  bacterial  fermenta- 
tion with  the  production  of  ammonia.  The  general  explanation  of 
the  effect  of  food  that  has  been  suggested  (Drechsel)  is  that  upon 
an  animal  diet  more  acids  are  formed  (from  the  oxidation  of  the 
sulphur  and  phosphorus  of  the  proteins)  than  in  the  case  of  the 
vegetable  foods  in  which  the  alkaline  salts  of  the  vegetable  acids 
give  rise  on  oxidation  in  the  body  to  alkaline  carbonates.  The 

*  Henderson  and  Palmer,  "Journal  of  Biological  Chemistry,"  13,  394,  1912. 


KIDNEY    AND    SKIN    AS    EXCRETORY    ORGANS.  851 

secretory  activity  of  the  kidney  serves  to  maintain  a  normal  bal- 
ance between  the  acid  and  basic  equivalents  in  the  blood,  and  the 
fact  that  on  an  ordinary  mixed  diet  the  urine  has  an  acid  reaction 
indicates  that  the  acids  formed  in  the  body  during  metabolism 
must  exceed  the  bases.  It  is  evident  from  this  consideration  that 
the  kidneys  take  an  important  part  in  maintaining  the  substantial 
neutrality  of  the  blood.  The  kidneys  and  the  lungs  co-operate  in 
this  function,  the  former  by  the  secretion  of  the  excess  of  acid  salts 
and  organic  acids  or  the  excess  of  bases,  as  the  case  may  be,  the 
latter  by  the  elimination  of  carbon  dioxid. 

The  composition  of  the  urine  is  very  complex.  In  addition  to 
the  water  and  inorganic  salts  the  following  elements  are  important, 
namely,  urea,  the  purin  bodies  (uric  acid,  xanthin,  hypoxanthin), 
creatinin,  hippuric  acid,  oxalic  acid  (calcium  oxalate),  several 
conjugated  sulphates  and  conjugated  glycuronates,  several  aromatic 
oxyacids  and  nitrogenous  acids,  fatty  acids,  dissolved  gases  (N 
and  CO2),  and  the  urinary  pigments  urochrome  and  urobilin.  This 
list  is  not  complete;  a  number  of  additional  substances  have  been 
described  as  occurring  constantly  or  occasionally  in  traces  within 
the  limits  of  health,  and  some  substances  are  secreted  whose  compo- 
sition is  unknown.  Under  pathological  conditions  the  composition 
may  be  still  further  modified.  The  complexity  of  the  composition 
may  be  understood  when  it  is  recalled  that  through  this  organ  are 
eliminated  some  of  all  the  end-products  formed  in  the  various  tis- 
sues, together  with  products  arising  from  bacterial  fermentation 
in  the  gastro-intestinal  canal  and  various  more  or  less  foreign  sub- 
stances taken  with  the  food.  It  is  not  possible  to  describe  all  the 
numerous  constituents  that  have  been  observed.  Attention  may 
be  directed  to  those  that  quantitatively  or  otherwise  are  of  chief 
physiological  interest. 

The  Nitrogen  Elimination  in  the  Urine. — In  the  metabolism  of 
the  usual  foodstuffs — carbohydrates,  fats,  and  proteins — the  end- 
products  of  their  destruction  or  physiological  oxidation  in  the  body 
are  water,  carbon  dioxid,  and  nitrogenous  waste  products  (and 
sulphates  and  phosphates  from  the  sulphur  and  phosphorus  in  the 
proteins) .  The  water  is  eliminated  in  the  urine,  the  sweat,  saliva, 
etc.,  and  the  expired  air.  The  C02  is  eliminated  in  the  expired 
air,  and  in  smaller  part  in  dissolved  form  in  the  secretions  (sweat, 
urine) .  The  nitrogenous  excretion,  representing  the  breaking  down 
of  protein  material,  is  found  in  minute  part  in  the  sweat,  to  a  larger 
extent  in  the  feces,  but  in  by  far  the  main  amount  in  the  urine. 
In  all  problems  concerning  protein  metabolism  in  the  body,  both 
as  regards  its  character  and  extent,  the  quantitative  study  of  this 
excretion  is  of  paramount  importance.  In  order  to  determine  the 
total  amount  of  protein  metabolism  it  is  customary  to  determine 


852  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

the  total  nitrogen  eliminated  in  the  urine,  without  regard  to  its 
specific  form.  This  determination  is  made  usually  by  the  method 
of  Kjeldahl.  The  total  weight  of  nitrogen  multiplied  by  6.25 
gives  the  amount  of  protein  broken  down,  since  nitrogen  forms,  on 
the  average,  16  per  cent,  of  the  weight  of  the  protein  molecule.  In 
an  average-sized  man  the  total  nitrogen  eliminated  in  a  day  varies, 
let  us  say,  between  14  and  18  gms.,  which  would  correspond  to  88 
and  117  gms.  of  protein.  It  is  often  necessary  to  distinguish 
between  the  forms  in  which  this  nitrogen  is  eliminated,  and  in 
analyses  of  the  urine  for  qualitative  purposes,  that  is,  to  throw 
light  on  the  kind  of  metabolism  taking  place  in  the  body,  the  fol- 
lowing division  or  partition  of  the  nitrogen  is  made  according  to 
special  methods  of  analysis:* 

1.  The  urea  nitrogen,  that  is,  the  amount  of  nitrogen  excreted 
in  the  form  of  urea.     The  amount  of  nitrogen  eliminated  in  this 
form  varies  with  the  amount  of  protein  food  in  the  diet,  as  is  ex- 
plained below.     Under  normal  conditions  it  constitutes  80  per 
cent,  or  more  of  the  total  nitrogen. 

2.  The  ammonia  nitrogen,  the  nitrogen  excreted  in  the  form  of 
ammonia  salts  which  liberate  free  ammonia  on  the  addition  of  a 
fixed  alkali.     Under  normal  conditions  it  constitutes  from  4  to  5 
per  cent,  of  the  total  nitrogen.     The  amount  of  ammonia  nitrogen 
may  be  much  increased  under  certain  pathological  conditions  in 
which  there  is  a  tendency  toward  acidosis,  that  is  to  say,  toward 
the  production  of  a  dangerous  excess  of  acids  in  the  body  which, 
while  not  altering  perceptibly  the  actual  hydrogen-ion  concentra- 
tion of  the  blood,  does  reduce  the  amount  of  alkali  reserve  that 
serves  to  protect  the  reaction.     The  ammonia  serves  to  neutralize 
these  acids.     As  is  described  below  in  connection  with  the  dis- 
cussion of  the  origin  of  urea,  ammonia  is  formed  constantly  in  the 
body  in  the  hydrolysis  of  the  protein  molecule  and  in  the  process 
of  deaminization  of  the  amino-acids  arising  from  this  hydrolysis. 
For  the  most  part  the  ammonia  thus  formed  combines  with  some 
of  the  carbonic  acid  arising  from  the  oxidative  processes  to  form 
ammonium  carbonate,  which  is  then  converted  to  urea  and  secreted. 
But  it  may  be  used  to  neutralize  other  acids  as  well,  and  in  this 
respect  constitutes  one  of  the  important  means  by  which  vthe  normal 
reaction  of  the  body  liquids  is  safeguarded. 

3.  The  creatinin  nitrogen,  the  nitrogen  excreted  in  the  form  of 
creatinin.     An  average  estimate  for  the  human  urine  is  3.6  per 
cent,   of  the  total  nitrogen.     This   product   has  also  a  special 
metabolic  significance,  which  is  discussed  below. 

4.  The  purin  nitrogen,  the  nitrogen  excreted  in  the  form  of 
purin    compounds    (uric    acid,    xanthin,    hypoxanthin) .      These 

*Folin,  "American  Physiological  Journal,"  13,  45,  1905. 


KIDNEY    AND    SKIN    AS    EXCRETORY    ORGANS.  853 

products  give  an  index  of  the  amount  of  nucleic  acid  metabolized 
in  the  body,  and  the  nitrogen  thus  eliminated  may  be  given  an 
average  value  of  1  to  2  per  cent,  of  the  total  nitrogen. 

5.  The  Amino-acid  Nitrogen.  *     Some  of  the  nitrogen  is  excreted 
in  the  form  of  amino-acids,  either  free  or  combined.     An  example 
of  the  combined  form  is  the   compound   hippuric  acid,  which 
consists  of  benzoic  acid  in  combination  with  amino-acetic  acid 
(glycin). 

6.  Unknown   Nitrogen.     Certain  nitrogenous  substances  are 
excreted  in  the  urine  whose  structure  and  physiological  significance 
are  as  yet  undetermined.     Among  these  substances  are  the  so- 
called  oxyproteic  acids  which  contain  both  nitrogen  and  sulphur. 
They  are  derived  presumably  from  the  metabolism  of  proteins,  but 
the  special  significance  to  be  attributed  to  them  cannot  be  stated. 
The  unknown  nitrogen  may  constitute  as  much  as  3  to  5  per  cent, 
of  the  total  nitrogen. 

Origin  and  Significance  of  Urea. — Urea  has  the  formula,  CO 
N2H4.     It   may  be  considered  as  an  amid  of  carbonic  acid,  and 

has,  therefore,  the  structural  formula  of  CO^NH2.  It  occurs  in  the 
urine  in  relatively  large  quantities  (2  per  cent.).  As  the  total  quan- 
tity of  urine  secreted  in  twenty-four  hours  by  an  adult  male  may 
be  placed  at  from  1500  to  1700  c.c.,  it  follows  that  from  30  to  34 
gms.  of  urea  are  eliminated  from  the  body  during  this  period.  It 
is  the  most  important  of  the  nitrogenous  excreta  of  the  body,  the 
chief  end-product,  so  far  as  the  nitrogen  is  concerned,  of  the  phys- 
iological metabolism  of  the  proteins  of  the  foods  and  the  tissues. 
In  addition  to  the  urine,  urea  is  found  in  slight  quantities  in  other 
secretions — in  milk  (in  traces)  and  in  sweat.  In  the  latter  liquid 
the  quantity  of  urea  in  twenty-four  hours  may  be  quite  appreci- 
able— as  much,  for  instance,  as  0.8  gm. — although  such  a  large 
amount  is  found  only  after  active  exercise.  Urea  is  present 
normally  in  the  blood  in  an  amount  equal  to  27  to  28  mgms  to  100 
c.c.  of  blood  (0.028  per  cent.),  and  it  has  been  shown  that  the  tissues 
generally  contain  the  urea  in  about  the  same  concentration,  f 
In  fact,  the  urea  diffuses  into  the  tissues  with  great  ease,  and  when 
for  any  reason  the  concentration  in  the  blood  varies  the  amount  in 
the  tissues  rises  or  falls  in  a  corresponding  way.  The  kidneys 
constantly  remove  the  urea  as  it  is  formed,  and  by  their  secretory 
activity  the  amount  of  urea  in  the  blood  is  kept  normally  at  the 
low  level  given  above.  When  the  kidneys  are  removed  the  amount 
of  urea  in  the  blood  rises,  showing  that  this  substance  is  formed 
elsewhere  in  the  body.  The  history  of  the  formation  of  urea  in  the 

*  Henriques  and  Sorenson,  "Zeitschrift  fur  physiol.  Chemie,"  64, 128, 1910. 
t  Marshall  and  Davis,  "Journal  of  Biological  Chemistry,"  18,  53,  1914. 


854  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

body  is  not  entirely  known,  but  three  sources  of  origin  may  be 
stated  with  some  positiveness. 

1.  Urea  arises  from  ammonia  salts  which,  in  the  liver,  are  con- 
verted to  urea  by  a  process  equivalent  to  dehydration.  It  has  long 
been  known  that  when  ammonium  carbonate  is  added  to  blood 
perfused  through  a  liver  it  is  converted  to  urea.*  The  reaction 
may  be  represented  as  follows: 


NH2 

Ammonium  carbonate.  Urea. 

Moreover,  the  experiments  made  by  Hahn,  Pawlow,  Massen,  and 
Nenckij  show  that  in  dogs  removal  of  the  liver  is  followed  by  a 
decrease  in  the  amount  of  urea  in  the  urine  and  an  increase  in  the 
ammonia  contents.  In  these  remarkable  experiments  a  fistula 
(Eck  fistula)  was  made  between  the  portal  vein  and  the  inferior 
vena  cava,  the  result  of  which  was  that  the  whole  portal  circulation  of 
the  liver  was  abolished,  the  organ  receiving  blood  only  by  way  of 
the  hepatic  artery.  If  now  the  latter  artery  was  ligated  and  the 
liver  was  cut  away  as  far  as  possible,  the  result  was  practically  a 
complete  extirpation  of  the  organ.  Later  investigations  t  showed 
that  in  normal  animals  the  ammonia  contents  of  the  blood  of  the 
portal  vein  may  be  three  to  four  times  as  great  as  in  arterial  blood, 
but  that  after  removal  of  the  liver  the  ammonia  in  the  general 
circulation  increases  to  a  point  equal  to  that  observed  for  the 
portal  blood  and  produces  symptoms  of  poisoning  which  may 
result  fatally.  It  would  seem,  therefore,  that  the  liver  protects  the 
body  from  the  poisonous  action  of  the  ammonia  compounds  by 
converting  them  to  urea,  while  in  the  same  process  some  of  the 
CO2  formed  in  the  body  is  neutralized  and  prepared  for  excretion. 
Now  in  the  normal  digestive  hydrolysis  of  proteins  brought 
about  by  the  successive  action  of  pepsin,  trypsin,  and  erepsin  the 
protein  material  is  split  largely  or  entirely  into  its  constituent 
elements  and  its  nitrogen  appears  mainly  in  the  form  of  the 
amino-acids,  but  to  some  extent  also  probably  as  ammonia.  In 
addition,  there  is  evidence  that  some  ammonia  is  formed  in  the 
large  intestine,  as  the  result  of  the  action  of  the  putrefactive 
bacteria.  The  ammonia  produced  in  these  ways  is  probably 
carried  to  the  liver  and  there  converted  to  urea.  In  what  form  the 
ammonia  exists  in  the  blood  is  not  positively  known;  it  may  be 
present  as  a  carbonate  or  possibly,  as  some  observers  have  thought, 
as  a  carbamate.  Ammonium  carbamate  might  be  changed  to 
urea  according  to  the  following  reaction  : 

*  Schroeder,  "Archiv  f.  exp.  Pathol.  u.  Pharmakol.,"  vols.  xv.  and  xix., 
1882,  1885. 

t  See  "Archiv.  f.  exp.  Pathol.  Pharmakol.,"  1893,  xxxii.,  161. 

|  See  Nencki  and  Pawlaw,  "Archives  des  sciences  biologiques,"  v.,  213. 


KIDNEY   AND    SKIN    AS    EXCRETORY    ORGANS.  855 


4       TT  d 
NH2~  NH2" 

Ammonia  salts  may  arise  similarly  in  the  tissues  of  the  body, 
since  the  cells  contain  intracellular  enzymes  capable  of  causing 
hydrolytic  cleavage  of  the  protein  molecule.  So  far  as  ammonia  is 
produced  in  this  way,  it  may  be  converted  to  urea  by  the  action  of 
the  liver  and  possibly  by  a  similar  action  in  other  tissues. 

2.  Urea  arises  from  the  monamino-acids  by  a  process  of  deamin- 
ization,  whereby  the  NH2  group  is  converted  to  ammonia  and 
then  probably  to  urea.  In  the  digestion  of  protein  in  the  alimen- 
tary canal  amino-acids  are  formed  in  quantity.  The  current  belief 
in  physiology  is  that  these  amino-acids  are  carried  in  the  blood  to 
the  various  tissues  and  are  there  resynthesized  in  part  to  form  the 
characteristic  protein  of  the  tissue.  The  tissues  pick  and  choose  the 
several  amino-acids  necessary  for  their  reconstruction  or  growth. 
The  amino-acids  not  so  used  have  their  NH2  group  removed  by 
the  process  of  deaminization,  leaving  behind  an  organic  acid  or 
oxyacid  which  is  of  further  use  in  nutrition,  for  example,  as  a 
source  for  the  production  of  sugar  (p.  825).  The  general  nature  of 
the  process  is  represented  by  the  conversion  of  alanin  to  lactic  acid. 

CH3CHNH2COOH  +  H2O  =  NH3  +  CH3CHOHOCOH. 

There  is  evidence  to  show  that  this  process  of  deaminization,*  as 
well  as  the  further  conversion  of  the  ammonia  to  urea,  takes  place 
in  the  liver,  although  it  is  quite  possible  that  both  functions  may 
be  exhibited  by  other  tissues  as  well.  On  this  view  we  can  under- 
stand why  the  amount  of  urea  eliminated  in  the  urine  rises  and  falls 
with  the  amount  of  protein  taken  as  food.f  On  a  large  protein 
diet  the  amount  of  nitrogenous  material  supplied  is  in  excess  of  the 
amount  needed  for  tissue  construction.  It  may  be  supposed  that 
the  excess  nitrogen  is  promptly  removed  and  excreted  as  urea 
according  to  the  process  described  above.  It  seems  probable  that 
the  larger  part  of  the  urea  actually  found  in  the  urine  under  normal 
conditions  comes  in  this  way  rather  directly  from  the  food  so  far 
as  its  nitrogen  is  concerned.  The  ammonia  formed  in  this  way 
might  be  toxic  to  the  body,  but,  as  we  have  seen,  it  is  readily 
neutralized  by  the  C02  to  form  ammonium  carbonate,  and  this,  in 
turn,  is  easily  dehydrated  to  form  urea.  On  the  other  hand,  it  may 
be  assumed  that  this  source  of  ammonia  furnishes  the  body  with  a 
means  for  safeguarding  its  reaction  under  those  abnormal  condi- 
tions in  which  there  is  an  overproduction  of  fixed  organic  acids. 
But  on  the  lowest  protein  diet  or  in  starvation,  when  the  body  is 

*  Van  Slyke  and  Meyer,  "Journal  of  Biological  Chemistry,"  16,  187,  et  seq., 
1914. 

t  Folin,  "American  Journal  of  Physiology,"  13,  117,  1905. 
j  "Zeitschrift  f.  physiol.  Chemie,"  1904,  xlii.,  181. 


856  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

living  on  its  own  tissues,  urea  continues  to  be  formed,  so  that  in 
part  the  urea  of  the  urine  represents  nitrogen  which  has  prob- 
ably arisen  from  the  destruction  of  protein  tissue.  The  inter- 
mediate steps  in  this  latter  process  are  not  definitely  known,  but 
probably  they  are  analogous  to  those  described,  that  is  to  say,  the 
protein  passes  through  the  stage  of  amino-acids  and  subsequently 
undergoes  deaminization. 

3.  Urea  arises  from  the  arginin,  formed  in  the  cleavage  of  the 
protein  molecule  by  conversion  of  the  contained  guanidin  radicle. 
Kossel  and  Dakin  *  have  demonstrated  the  existence  of  a  ferment, 
present  in  the  liver  especially,  but  found  also  in  the  kidney,  thy- 
mus,  muscle,  etc.,  arginase,  which  is  capable  of  splitting  arginin 
into  urea  and  ornithin.  The  reaction  may  be  represented  by  the 
following  equation: 


Arginin  (guanidin-diamino-valerianic  acid).  Urea.         Diamino-valerianic  acid. 

Unlike  cases  1  and  2,  the  urea  in  this  instance  is  formed  from  the 
guanidin  residue  contained  in  the  arginin  and  not  from  the  amino- 
group.  Since  arginin  constitutes  one  of  the  split-products  of  the 
protein  during  digestion  and  probably  also  one  of  the  split-products 
in  the  metabolism  of  the  proteins  of  the  tissues,  there  is  reason  to 
believe  that  part  of  the  urea  actually  formed  in  the  body  arises  by 
this  method.  It  is  possible  that  by  some  similar  method  the 
nitrogen  of  the  heterocyclic  radical  in  other  amino-acids  (imidazol, 
indpl,  pyrol)  may  give  rise  to  urea,  but  nothing  is  known  in  regard 
to  this  possibility. 

Origin  and  Significance  of  the  Purin  Bodies  (Uric  Acid, 
Xanthin,  Hypoxanthin,  Adenin,  Guanin).  —  These  bodies  are 
related  chemically,  and  appear  also  to  have  a  common  physiological 
significance.  Their  chemical  relations  have  been  described  by 
Emil  Fischer,  to  whom  we  owe  the  term  purin  bodies.  Fischer 
pointed  out  that  these  and  other  substances  belonging  to  this 
group  have  a  common  nucleus': 
N  —  C 

C      C  —  Nv         which     he     named     the     purin     nucleus.     The 


hydrogen  compound  of  this  nucleus  would  be  designated  as  purin, 

N  —  CH 

and  would  have  the  formula:    HC      C— NH     ,  C5H4N4.    Addi- 


tion    of    an    atom    of    oxygen    gives    hypoxanthin,    C5H4N40: 
""Zeitschrift  f.  physiol.  Chemie,"  1904,  xlii.,  181. 


KIDNEY    AND    SKIN    AS    EXCRETORY    ORGANS.  857 

HN  —  CO 

HC       C  —  NH 

Jlj. ^       ^>CIL.    Addition  of  two  atoms  of  oxygen  gives  xan- 

HN  — CO 

thin,  C5H4N402:    CO      C  — NH 

jj'jj |l N\CH.     And  addition  of  three  atoms 

HN  — CO 

of  oxygen  gives  uric  acid,  C5H4N4O3:   CO       C  — NH        ,  which 

HN  —  C  —  NH 

from  this  standpoint  might  be  named  trioxypurin.  If  one  of  the  H 
atoms  in  the  purin  is  substituted  by  an  ammo-group,  NH2,  the  com- 
pound, adenin  (C5H5N5),  is  obtained,  and  the  substitution  of  an 
NH2  group  in  hypoxanthin  gives  the  compound  guanin  (C5H5N50). 
Moreover,  caffein,  the  active  principle  of  coffee  and  tea,  and  theo- 
bromin,  the  active  principle  of  cocoa,  are  respectively  trimethyl 
and  dimethyl  compounds  of  xanthin.  We  have  to  distinguish, 
therefore,  three  classes  of  purin  compounds,  namely,  the  oxypurins, 
comprising  monoxypurin  or  hypoxanthin,  dioxypurin  or  xanthin, 
and  trioxypurin  or  uric  acid;  the  aminopurins,  comprising  adenin  or 
aminopurin  and  guanin  or  aminohypoxanthin,  and  the  methyl- 
purins,  comprising  caffein  or  trimethyl  xanthin  (C8H10N4O2  or  C5H- 
(CH3)3N402)  and  theobromin  or  dimethyl  xanthin  (C7H8N4O2  or 
C5H2(CH3)2N4O2).  Uric  acid,  xanthin,  and  hypoxanthin  are  found 
constantly  in  the  urine  and  in  the  feces  small  amounts  of  xanthin, 
hypoxanthin,  adenin,  and  guanin  may  also  occur.  It  has  been 
pointed  out  *  that  these  substances  come  partly  from  purin  bodies 
taken  as  food.  If  materials  containing  the  purin  bodies,  such  as 
meat,  are  fed,  these  bodies  are  excreted  in  part  in  the  urine.  It  is 
proposed  to  designate  the  uric  acid,  etc.,  that  has  this  origin  as  the 
exogenous  purin  material.  A  portion  of  the  amount  daily  secreted 
comes,  however,  from  a  metabolism  of  the  protein  material  of  the 
body,  and  this  portion  may  be  distinguished  as  the  endogenous  purin 
bodies.  This  latter  amount  is  found  to  be  practically  constant, 
0.15  to  0.20  gm.  per  day  for  any  one  individual,  and  the  amount  is 
not  affected  by  changes  in  the  quantity  or  character  of  the  food, 
but  varies  within  certain  limits  with  the  manner  of  life.  Evidently 
the  endogenous  purin  nitrogen  represents  a  special  metabolism, 
propably  of  the  living  tissues,  that  goes  on  independently,  in  great 
measure,  of  the  mere  oxidation  of  food.  Evidence  has  accu- 
mulated which  shows  that  the  purin  bodies  of  the  urine  repre- 
sent the  end-products  of  the  metabolism  of  nucleic  acid,  either  the 

*  See  Burian  and  Schur, "  Archiv  f .  die  gesammte  Physiologic,"  94, 273, 1903. 


858  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

nucleic  acid  of  the  tissues  or  the  nucleic  acid  of  the  food.*  Nucleic 
acid  exists  in  the  body  in  more  or  less  definite  combination  with 
protein  to  form  the  so-called  nucleoproteins  which  are  supposed  to 
occur  chiefly  in  the  nuclei  of  the  cells.  The  nucleic  acid  itself  on 
hydrolysis  yields  several  nitrogenous  bases,  guanin,  adenin,  cyto- 
sin,  and  thymin,  in  addition  to  phosphoric  acid  and  a  carbohydrate. 
Guanin  and  adenin  are  purin  bases,  while  the  cytosin  and  thymin 
have  a  different  structure  and  are  known  as  pyrimidin.  bases. 
Within  the  molecule  of  nucleic  acid  these  constituents  are  grouped, 
so  that  each  nitrogenous  base  is  united  to  a  carbohydrate  and  a 
phosphoric-acid  complex.  Such  a  grouping  is  designated  as  a 
nucleotide,  and  nucleic  acid  is  frequently  spoken  of  as  a  tetranucleo- 
tide  whose  structure  may  be  represented  diagrammatically  as 
follows: 

Adenin-carbohydrate-phosphoric  acid . 

Guanin-carbohydrate-phosphoric  acid. 

Cy tosin-carbohydrate-phosphoric  acid . 


Cytosin-carbohydrate-phosph< 
Thymin-carbohydrate-phosph 


oric  acid. 

The  breaking  down  of  the  nucleic  acid  involves  the  action  of  a 
number  of  different  enzymes  and  the  story  is  complicated  and  not 
wholly  agreed  upon  by  the  different  workers.  It  is  supposed  that 
the  nucleic  acid  is  liberated  from  its  combination  with  protein  by 
the  action  of  the  known  proteolytic  enzymes,  such  as  pepsin  or 
trypsin  or  the  similar  autolytic  enzymes  in  the  tissues.  For  the 
destruction  of  the  nucleic  acid  itself  there  is  a  series  of  special 
enzymes  whose  action  as  described  by  Jones  is  essentially  as  follows  : 

1.  The  tetranucleotide  is  split  into  two  dinucleo  tides  (purin  and 
pyrimidin)  by  the  enzyme  tetranuclease.     The  further  history  of 
the  pyrimidin  nucleotides  is  not  known. 

2.  The  purin  nucleotides  are  split  by  two  enzymes,  phospho- 
nuclease  and  purin-nuclease.     The  former  splits  off  phosphoric 
acid  and  leaves  the  purin  bases  in  combination  with  the  carbo- 
hydrate, giving  two  compounds  known  as  nucleosides,  namely, 
adenosin  and  guanosin.     The  purin-nuclease  splits  off  adenin  and 
guanin  in  free  form  . 

3.  The  four  substances,  adenin,  g-uanin,  adenosin,  and  guanosin, 
are  acted  upon  by  corresponding  deaminizing  enzymes,  adenase, 
guanase,  adenosin-deaminase,  and  guanosin-deaminase,  and  con- 
verted to  oxypurins.     For  the  adenin  and  guanin  the  reaction  is  as 

follows  : 

C6H5N5  +  H2O  =  C5H4N4O  +  NH3 

Adenin.  Hypoxanthin. 


+  H20  =  C6H4N402  +  NH3 

Guanin.  Xanthin. 

*For  a  full  account  and  the  literature  consult  Jones,  "Nucleic  Acids  — 
Their  Chemical  Properties  and  Physiological  Conduct,"  1914. 


KIDNEY  AND    SKIN    AS    SECRETORY    ORGANS.  859 

The  nucleosides  (adenosin  and  guanosin)  may  first  be  converted 
to  the  corresponding  oxy-compounds  (xanthosin  and  inosin),  and 
then  by  hydrolysis  the  carbohydrate  is  split  off  with  the  liberation 
of  xanthin  and  hypoxanthin. 

4.  The  xanthin  and  hypoxanthin,  under  the  influence  of  an  oxi- 
dase  (xanthinoxidase),  are  in  part  oxidized  to  uric  acid,  CsEUN^a. 
In  man  this  oxidase  seems  to  occur  only  in  the  liver,  so  that  the 
immediate  production  of  uric  acid  must  be  referred  to  this  organ. 

5.  In  man  the  uric  acid,  'xanthin,  and  hypoxanthin  represent 
the  final  end-products  of  the  metabolism  of  the  nucleic  acid  or, 
rather,  of  the  purin  nucleotide  portion  of  its  molecule,  and  to 
the  extent  that  they  occur  in  the  urine  they  indicate  so  much 
nucleic  acid  broken  down.     In  the  other  mammals  the  oxidation 
process  goes  a  step  further  —  the  uric  acid  is  converted  to  allantoin 
by  an  oxidase  known  as  uricolytic  enzyme  or  uricase,  whose  action 
may  be  represented  by  the  equation  : 


403  +  H20  +  O  =  C4H6N403  +  CO2 

Uric  acid.  Allantoin. 

Origin   and    Significance    of   the    Creatinin   and    Creatin.— 

Creatinin  (C4H7N3O)  occurs  in  the  urine,  and  it  was  formerly  as- 
sumed that  it  is  derived  from  the  creatin  (C4H9N3O2)  found  in 

/NH  -  CO 
muscle.     Its  structural  formula  is  given  as  NHC^  I     and  its 

XN(CH3)CH2 

chemical  relations  are  indicated  by  the  fact  that  it  may  be  prepared 
synthetically  from  methyl-glycocoll  and  cyanamid  —  that  is,  the 
union  of  these  two  substances  gives  creatin,  from  which  in  turn 
creatinin  may  be  obtained  by  loss  of  a  molecule  of  water. 


N=C-NH2    +     NH(CH3)CH2COOH 

Cyanamid.  Methyl-glycocoll.  Creatin. 

Creatinin  occurs  in  the  urine  constantly  and  in  amounts  equal  to 
1  to  2  gms.  per  day,  or,  according  to  Sh'affer,*  there  is  an  excretion 
of  from  7  to  11  mg.  of  creatinin  nitrogen  per  kilogram  of  body- 
weight.  Next  to  the  urea  and  the  ammonia  compounds  it  forms 
the  most  important  of  the  known  nitrogenous  constituent  of  the 
urine.  Its  physiological  history  is  imperfectly  known.  Under 
constant  conditions  of  life  the  amount  of  creatinin  formed  in  the 
body  is  independent  of  the  quantity  of  protein  eaten,  and  this 
fact  indicates  (Folin)  that  it  represents  an  end-product  of  the 
metabolism  of  living  or  organized  protein  tissue  rather  than  one 
of  the  results  of  the  metabolism  of  the  food  protein.  This  con- 
clusion is  strengthened  by  the  fact  that  in  fevers  and  other  patho- 

*  Consult  Shaffer,  "American  Journal  of  Physiology/'  33,  1,  1908. 


860  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

logical  conditions  in  which  there  is  an  increased  breaking  down  of 
tissues  the  creatinin  excretion  is  increased.*  Creatinin  is  present 
in  small  amounts  in  the  blood,  1  to  2  mgms  per  100  gms.  of  blood, 
and  in  somewhat  larger  amount  in  the  muscular  tissue.  Creatin, 
on  the  other  hand,  is  present  in  muscular  tissue  to  a  relatively  large 
per  cent.,  0.5  to  0.6  gm.  per  100  gms.  of  muscle,  although  Folin 
contends  t  that  this  large  yield  is  due  to  postmortem  changes  and 
that  in  the  living  muscle  little  or  none  is  present  in  free  condition. 
Creatin  occurs  in  the  blood  in  small  amounts,  but  in  the  urine  it  is 
not  normally  present  so  far  as  the  normal  adult  man  is  concerned. 
In  children,  however,  it  is  constantly  .present  in  the  urine,  and  in 
women  it  is  said  to  occur  after  menstruation,  during  pregnancy, 
and  in  the  puerperium.t  So  also  in  mankind  the  urine  shows  the 
presence  of  creatin  during  starvation  or  in  fevers.  It  has  not  been 
found  possible  to  interpret  satisfactorily  these  various  facts. 
According  to  one  view,  §  the  creatin  and  creatinin  are  related  and 
have  a  common  physiological  significance  in  regard  to  the  metabo- 
lism. The  creatin  is  regarded  as  an  end-product  of  the  break-down 
of  organized  or  living  protein  tissue.  It  is  produced  constantly  in 
the  tissues  and  is  normally  converted  to  creatinin  before  it  is  ex- 
creted in  the  urine.  Under  exceptional  conditions,  such  as  starva- 
tion or  fever,  the  disintegration  of  the  tissues  is  increased  and  the 
amount  of  creatin  produced  is  too  large  to  be  wholly  changed  to 
creatinin,  with  the  .result  that  both  creatin  and  creatinin  appear  in 
the  urine.  Other  observers  If  believe  that  the  metabolic  history  and 
significance  of  creatin  and  creatinin  are  different.  The  creatinin 
formed  in  the  tissues  represents  an  end-product  of  the  breaking 
down  of  the  organized  tissue  and,  indeed,  forms  an  index  of  the 
amount  of  this  tissue  wear  and  tear,  but  it  is  given  off  to  the  blood 
and  excreted  in  the  urine  as  creatinin.  The  creatin,  on  the  con- 
trary, while  also  constantly  formed  in  the  tissues  as  a  result  of  their 
metabolism,  is  not  converted  to  creatinin,  but  undergoes  some  fur- 
ther and  as  yet  unknown  metabolic  change.  When  creatin  is  fed 
to  a  man,  for  example,  it  is  not  excreted  in  the  urine  as  creatin  or 
as  creatinin,  but  is  used  in  some  way  in  the  body.  On  this  view 
the  significance  of  the  creatin  remains  undetermined)  and  its 
genesis  and  fate  are  also  left  unsettled,  except  so  far  as  to  deny  its 
conversion  to  creatinin. 

Hippuric  Acid. — This  substance  has  the  formula  C9H9N03.   Its 

*Hoogenhuyze  and  Verploegh,  "Zeitschrift  f.  physiol.  Chemie,"  57, 161, 
1908. 

t  Folin  and 

j  Krause, 

§  Mendel 
also  Meyers  and  Fine,  ibid.,  15,  283,  1913. 

1[  Folin  and  Krause,  loc.  cit.;  also  Benedict  and  Osterberg,    "Journal  of 
Biological  Chemistry,"  18,  195,  1914. 


KIDNEY    AND    SKIN    AS    EXCRETORY    ORGANS.  861 

molecular  structure  is  known,  since  upon  decomposition  it  yields 
benzole  acid  and  giycocoll,  and,  moreover,  it  may  be  produced 
synthetically  by  the  union  of  these  two  substances.  Hippuric  acid 
may  be  described,  therefore,  as  a  benzoyl-amino-acetic  acid  (CH2- 
NH[C6H5CO]COOH).  It  is  found  in  considerable  quantities  in  the 
urine  of  herbivorous  animals  (1.5  to  2.5  per  cent.),  and  in  much 
smaller  amounts  in  the  urine  of  man  and  of  the  carnivora.  In 
human  urine,  on  an  average  diet,  about  0.7  gm.  are  excreted  in 
twenty-four  hours.  If  the  diet  is  largely  vegetable,  this  amount  may 
be  much  increased.  This  last  fact  is  readily  explained,  for  it  has  been 
found  that  if  benzoic  acid  or  substances  containing  this  grouping 
are  fed  to  animals  they  appear  in  the  urine  as  hippuric  acid.  Evi- 
dently a  synthesis  occurs  in  the  body,  and  Bunge  and  Schmie- 
deberg  proved  conclusively  that  in  dogs  the  union  of  benzoic  acid 
and  giycocoll  to  form  hippuric  acid  takes  place  in  the  kidney 
itself.  Later  it  was  discovered*  that  the  same  synthesis  may  be 
effected  by  ground-up  kidney  tissue,  mixed  with  blood  and  kept 
under  oxygen  pressure.  It  seems  possible,  therefore,  that  the 
synthesis  is  due  to  some  specific  constituent  of  the  kidney  cells, 
possibly  an  enzyme.  Vegetable  foods  contain  benzoic  acid  com- 
pounds, and  we  can  understand,  therefore,  why  when  fed  they  in- 
crease the  hippuric  acid  output  of  the  urine.  Since  in  starving 
animals  or  animals  fed  upon  meat  hippuric  acid  is  still  present 
in  the  urine,  although  reduced  in  amount,  it  is  evident  that  it 
arises  in  part  as  a  result  of  the  body  metabolism.  The  physio- 
logical significance  of  this  nitrogenous  product  is  different  from 
those  previously  considered  in  that  it  does  not  represent  the 
result  of  a  special  metabolism  of  protein  food  or  protein  tissue, 
but  is  rather  a  provision  by  which  benzoic  acid  when  present 
in  the  food  or  formed  in  the  body  is  conjugated  with  glycin  and 
excreted. 

The  Conjugated  Sulphates  and  the  Sulphur  Excretion. — 
The  sulphur  excretion  of  the  urine  possesses  an  importance  similar 
to  that  of  nitrogen.  Sulphur  constitutes  an  element  in  most  of  the 
proteins,  and  in  some  form,  therefore,  it  will  be  represented  in  the 
end-products  of  protein  metabolism.  The  sulphur  elimination  in 
the  urine,  like  the  nitrogen  elimination,  has  been  taken  as  a  measure 
of  the  amount  of  protein  destruction.  In  the  urine  the  sulphur 
occurs  in  three  forms:  (1)  In  an  oxidized  form  as  inorganic  sul- 
phates. Some  of  the  sulphates  are  undoubtedly  derived  or  may  be 
derived  from  the  mineral  sulphates  ingested  with  the  food,  but  the 
larger  part  arises  from  the  oxidation  of  the  sulphur  of  the  proteins. 
(2)  The  so-called  conjugated  or  ethereal  sulphates  are  combinations 
between  sulphuric  acid  and  indoxyl,  skatoxyl,  phenol,  and  cresol, 

*  Bashford  and  Cramer,  "Zeitschrift  f.  physiol.  Chemie,"  35,  324, 1902. 


862  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

giving  us  phenolsulphuric  acid(C6H50SO2OH),  cresolsulphuric  acid 
(C7H7OS02OH),  indoxylsulphuric  acid  or  indican  (CgH^NOSOoOH), 
and  skatoxylsulphuric  acid  (C9H8NOSO2OH) .  The  indol,  skatol, 
phenol,  and  cresol  are  formed  in  the  large  intestine  as  a  result  of  bac- 
terial putrefaction.  They  are  eliminated  in  part  in  the  feces,  but 
in  part  are  absorbed  into  the  blood,  and  after  oxidation  are. 
conjugated  with  sulphuric  acid  and  eliminated  in  the  urine.  The 
process  of  conjugation  is  valuable  from  a  physiological  standpoint, 
as  it  converts  substances  having  an  injurious  action  into  harmless 
compounds.  It  should  be  added,  also,  that  to  a  small  extent  the 
phenol,  indoxyl,  and  skatoxyl  may  be  secreted  in  the  urine  as  con- 
jugated glucuronates, — that  is,  in  combination  with  glycuronic  acid 
(C6H10O7),  a  reducing  substance  closely  connected  with  dextrose. 
From  a  nutritional  standpoint  the  amount  of  these  substances  pres- 
ent furnishes  a  measure  of  the  extent  of  protein  putrefaction  in  the 
intestine,  by  virtue  of  the  indol  and  phenol  constituents.  All  con- 
ditions that  increase  the  putrefactive  processes  in  the  intestine 
are  accompanied  by  a  parallel  increase  in  the  ethereal  sulphates. 
By  virtue  of  the  sulphuric  acid  component  theee  bodies  represent 
also  one  of  the  forms  in  which  sulphur  is  excreted  from  the 
body.  (3)  Some  of  the  sulphur  in  the  urine  may  occur  in  unoxid- 
ized  form  as  sulphocyanid  or  as  ethyl-sulphide  (Abel)  ([C-jHJjS). 
Under  certain  pathological  conditions  (cystinuria)  some  sulphur  may 
be  excreted  in  the  form  of  cystin,  but  this  is  not  a  normal  con- 
stituent of  the  urine.  For  other  most  interesting  and  significant 
changes  in  the  composition  of  the  urine  under  pathological  condi- 
tions reference  must  be  made  to  special  works  upon  the  urine  or 
upon  pathological  chemistry. 

Water  and  Inorganic  Salts. — Water  is  lost  from  the  body 
through  three  main  channels, — namely,  the  lungs,  the  skin,  and 
the  kidney,  the  last  of  these  being  the  most  important.  The  quan- 
tity of  water  lost  through  the  lungs  probably  varies  within  small 
limits  only.  The  quantity  lost  through  the  sweat  varies,  of  course, 
with  the  temperature,  with  exercise,  etc.,  and  it  may  be  said  that 
the  amounts  of  water  secreted  through  kidney  and  skin  stand  in 
something  of  an  inverse  proportion  to  each  other;  that  is,  the  greater 
the  quantity  lost  through  the  skin,  the  less  will  be  secreted  by  the 
kidneys.  Through  these  three  organs,  but  mainly  through  the 
kidneys,  the  blood  is  being  continually  depleted  of  water,  and  the 
loss  must  be  made  up  by  the  ingestion  of  new  water.  When  water 
is  swallowed  in  excess  the  superfluous  amount  is  rapidly  eliminated 
through  the  kidneys,  and  there  is  some  evidence  (p.  849)  that  in 
this  case  the  excretion  of  the  excess  of  water  is  controlled  by  a 
special  hormone  found  in  the  small  intestine.  The  amount  of 
water  secreted  may  be  increased  by  the  action  of  diuretics,  such  as 
potassium  nitrate  and  caffein. 


KIDNEY  AND  SKIN  AS  EXCRETORY  ORGANS.        863 

The  inorganic  salts  of  urine  consist  chiefly  of  the  chlorids,  phos- 
phates, and  sulphates  of  the  alkalies  and  the  alkaline  earths.  It 
may  be  said,  in  general,  that  they  arise  partly  from  the  salts  ingested 
with  the  food,  and  are  eliminated  from  the  blood  by  the  kidney 
in  the  water  secretion;  and  in  part  they  are  formed  in  the  destruc- 
tive metabolism  that  takes  place  in  the  body,  particularly  that 
involving  the  proteins  and  related  bodies.  Sodium  chlorid  occurs 
in  the  largest  quantities,  averaging  about  15  gms.  per  day,  of 
which  the  larger  part,  doubtless,  is  derived  directly  from  the  salt 
taken  in  the  food.  The  phosphates  occur  in  combination  with  cal- 
cium and  magnesium,  but  chiefly  as  the  acid  phosphates  of  sodium 
or  potassium.  The  acid  reaction  of  the  urine  is  usually  attributed 
to  these  latter  substances.  The  phosphates  result  in  part  from  the 
destruction  of  phosphorus-containing  tissues  in  the  body,  but 
chiefly  from  the  phosphates  of  the  food.  The  sulphates  of  urine 
are  found  partly  in  an  oxidized  form  as  simple  sulphates  or  con- 
jugated with  organic  compounds,  as  described  above. 

Micturition. — The  urine  is  secreted  continuously  by  the  kid- 
neys, is  carried  to  the  bladder  through  the  ureters,  and  is  then  at 
intervals  finally  ejected  from  the  bladder  through  the  urethra  by 
the  act  of  micturition. 

Movements  of  the  Ureters. — The  ureters  possess  a  muscular  coat 
consisting  of  an  internal  longitudinal  and  external  circular  layer. 
The  contractions  of  this  muscular  coat  form  the  means  by  which 
the  urine  is  driven  from  the  pelvis  of  the  kidney  into  the  bladder. 
The  movements  of  the  ureter  have  been  carefully  studied  by  Engel- 
mann.*  According  to  his  description,  the  musculature  of  the  ureter 
contracts  spontaneously  at  intervals  of  ten  to  twenty  seconds  (rab- 
bit), the  contraction  beginning  at  the  kidney  and  progressing 
toward  the  bladder  in  the  form  of  a  peristaltic  wave  and  with  a 
velocity  of  about  20  to  30  mms.  per  second.  The  result  of  this 
movement  should  be  the  forcing  of  the  urine  into  the  bladder  in  a 
series  of  gentle,  rhythmical  spurts,  and  this  method  of  filling  the 
bladder  has  been  observed  in  the  human  being.  Suter  and  Mayerf 
report  some  observations  upon  a  boy  in  whom  there  was  ectopia 
of  the  bladder,  with  exposure  of  the  orifices  of  the  ureters.  The 
flow  into  the  bladder  was  intermittent  and  was  about  equal  upon  the 
two  sides  for  the  time  the  child  was  under  observation  (three  and 
a  half  days). 

The  causation  of  the  contractions  of  the  ureter  musculature  is 
not  easily  explained.  Engelmann  finds  that  artificial  stimulation 
of  the  ureter  or  of  a  piece  of  the  ureter  may  start  peristaltic  con- 

*  "Pfliiger's  Archiv  f.  die  gesammte  Physiologic,"  2,  243,  1869,  and  4,  33; 
see  also  Lucas,  "American  Journal  of  Physiology,"  17,  392,  1906. 

t  "Archiv  f.  exper.  Pathologic  und  Pharmakologie,"  32,  241,  1893. 


864  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

tractions  which  move  in  both  directions  from  the  point  stimulated. 
He  was  not  able  to  find  ganglion  cells  in  the  upper  two-thirds  of  the 
ureter  and  was  led  to  believe,  therefore,  that  the  contraction  orig- 
inates in  the  muscular  tissue  independently  of  extrinsic  or  intrinsic 
nerves,  and  that  the  contraction  wave  propagates  itself  directly 
from  muscle  cell  to  muscle  cell,  the  entire  musculature  behaving 
as  though  it  were  a  single,  colossal,  hollow  muscle-fiber.  Efforts 
to  show  a  regulatory  action  upon  these  movements  through  the 
central  nervous  system  have  so  far  given  negative  results. 

Movements  of  the  Bladder. — The  bladder  contains  a  muscular 
coat  of  plain  muscle  tissue,  which,  according  to  the  usual  descrip- 
tion, is  arranged  so  as  to  make  an  external  longitudinal  coat  and  an 
internal  circular  or  oblique  coat.  A  thin,  longitudinal  layer  of 
muscle  tissue  lying  to  the  interior  of  the  circular  coat  is  also  de- 
scribed. The  separation  between  the  longitudinal  and  circular 
layers  is  not  so  definite  as  in  the  case  of  the  intestine;  they  seem, 
in  fact,  to  form  a  continuous  layer,  one  passing  gradually  into  the 
other  by  a  change  in  the  direction  of  the  fibers.  At  the  opening  of 
the  bladder  into  the  urethra,  the  musculature  in  the  submucosa  is 
strengthened  to  form  a  ring  around  the  orifice  and  along  the  begin- 
ning of  the  urethra  which  is  supposed  to  function  as  a  sphincter,  the 
internal  sphincter  or  sphincter  vesicce  internus.  Around  the  urethra, 
in  the  prostate  and  membranous  portions,  is  a  circular  layer  of 
striated  muscle  that  is  frequently  designated  as  the  external 
sphincter  or  sphincter  urethrae.  The  urine  brought  into  the 
bladder  accumulates  within  its  cavity  to  a  certain  limit.  It  is 
prevented  from  escaping  through  the  urethra  by  a  tonic  contrac- 
tion of  the  internal  sphincter.  When  the  accumulation  becomes 
greater  the  external  sphincter  may  be  brought  into  action.  Back- 
flow  of  urine  from  the  bladder  into  the  ureters  is  effectually  pre- 
vented by  the  oblique  course  of  the  ureters  through  the  wall  of 
the  bladder.  Owing  to  this  circumstance,  pressure  within  the  blac^- 
der  serves  to  close  the  mouths  of  the  ureters,  and,  indeed,  the  more 
completely,  the  higher  the  pressure.  At  some  point  in  the  filling 
of  the  bladder  the  pressure  is  sufficient  to  arouse  a  conscious  sen- 
sation of  fullness  and  a  desire  to  micturate.  Under  normal  condi- 
tions the  act  of  micturition  follows.  It  consists  essentially  in  a 
strong  contraction  of  the  bladder,  with  a  simultaneous  relaxation 
of  the  internal  sphincter,  and  of  the  external  sphincter  also  if  this 
latter  is  in  contraction. 

The  force  of  this  contraction  is  considerable,  as  is  evidenced  by 
the  height  to  which  the  urine  may  spurt  from  the  end  of  the  urethra. 
According  to  Mosso,  the  contraction  may  support,  in  the  dog,  a 
column  of  liquid  two  meters  high.  The  contractions  of  the  blad- 
der may  be  and  usually  are  assisted  by  contractions  of  the  walls 


KIDNEY    AND    SKIN    AS    EXCRETORY    ORGANS.  865 

of  the  abdomen,  especially  toward  the  end  of  the  act.  As  in  defeca- 
tion and  vomiting,  the  contraction  of  the  abdominal  muscles,  when 
the  glottis  is  closed  so  as  to  keep  the  diaphragm  fixed,  serves  to  in- 
crease the  pressure  in  the  abdominal  and  pelvic  cavities,  and  thus 
assists  in  or  completes  the  emptying  of  the  bladder.  It  is, 
however,  not  an  essential  part  of  the  act  of  micturition.  The  last 
portions  of  the  urine  escaping  into  the  urethra  are  ejected,  in  the 
male,  in  spurts  produced  by  the  rhythmical  contractions  of  the 
bulbocavernosus  muscle. 

The  act  of  micturition  as  it  takes  place  in  man  is  pictured  by 
Rehfisch*  as  follows:  As  the  urine  accumulates  in  the  bladder  the 
pressure-stimulation  of  the  sensory  fibers  leads  to  a  reflex  stimu- 
lation of  the  internal  sphincter.  Further  accumulation  by  a  pres- 
sure effect  on  the  sensory  fibers  causes  reflex  contractions  of  the 
muscle  of  the  bladder,  and  the  additional  sensory  stimuli  produced 
by  these  contractions  spreading  upward  from  the  lower  center  occa- 
sion the  conscious  desire  to  urinate.  In  the  adult  at  least  the 
urination  takes  place  by  a  voluntary  act,  which  consists  in  an  inhi- 
bition of  the  tonus  center  in  the  lumbar  cord,  whose  reflex  stimula- 
tion has  up  to  this  point  maintained  the  tonic  contraction  of  the 
internal  sphincter.  The  effect  of  this  inhibition  is  to  relax  the 
sphincter  and  to  allow  the  bladder  to  empty  itself  by  its  reflex 
contraction,  aided  perhaps  by  a  voluntary  contraction  of  the  ab- 
dominal muscles.  During  the  emptying  of  the  bladder  the  process 
can  be  brought  to  a  stop  voluntarily  by  removing  the  inhibition, 
thus  allowing  the  internal  sphincter  to  contract  and  shut  off  the 
flow.  Rehfisch  considers  that  the  external  sphincter  (and  compres- 
sor urethrse)  play  a  relatively  small  role,  serving  as  a  reserve  mech- 
anism to  aid  in  the  closure  of  the  urethra. 

Mosso  and  Pellacanif  have  made  experiments  upon  women  in 
which  a  catheter  was  introduced  into  the  bladder  and  connected 
with  a  recording  apparatus  to  measure  the  volume  of  the  bladder. 
Their  experiments  indicate  that  the  sensation  of  fullness  and  desire 
to  micturate  come  from  sensory  stimulation,  in  the  bladder  itself, 
caused  by  the  pressure  of  the  urine.  They  point  out  that  the 
bladder  is  very  sensitive  to  reflex  stimulation;  that  every  psychical 
act  and  every  sensory  stimulus  is  apt  to  cause  a  contraction  or  in- 
creased tone  of  the  bladder.  The  bladder  is  therefore  subject  to 
continual  changes  in  size  from  reflex  stimulation,  and  the  pressure 
within  it  will  depend  not  simply  on  the  quantity  of  urine,  but  on 
the  condition  of  tone  of  its  muscles.  At  a  certain  pressure  the 
sensory  nerves  are  stimulated  and  under  normal  conditions  mictu- 
rition ensues.  We  may  understand,  from  this  point  of  view,  how  it 

*  Virchow's  "Archiv  f.  path.  Anat.,"  etc.,  150,  111,  1897. 
t  "Archives  italiennes  de  biologic,"  1,  1882. 
55 


866  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

happens  that  we  have  sometimes  a  strong  desire  to  micturate  when 
the  bladder  contains  but  little  urine, — for  example,  under  emotional 
excitement.  In  such  cases  if  the  micturition  is  prevented,  probably 
by  the  action  of  the  external  sphincter,  the  bladder  may  sub- 
sequently relax  and  the  sensation  of  fullness  and  desire  to  micturate 
'pass  away  until  the  urine  accumulates  in  sufficient  quantity,  or  the 
pressure  is  again  raised  by  some  circumstance  which  causes  a  reflex 
contraction  of  the  bladder. 

Nervous  Mechanism. — According  to  Langley  and  Anderson,*  the 
bladder  in  cats,  dogs,  and  rabbits  receives  motor  fibers  from  two 
sources:  (1)  From  the  lumbar  nerves,  the  fibers  passing  out  in  the 
second  to  the  fifth  lumbar  nerves  and  reaching  the  bladder  through 
the  sympathetic  chain  and  the  inferior  mesenteric  ganglion  and 
the  hypogastric  nerves  and  plexus  (Fig.  287).  Stimulation  of 
these  nerves  causes  a  comparatively  feeble  contraction  of  the  blad- 
der followed  by  an  inhibition.  (2)  From  the  sacral  spinal  nerves, 
the  fibers  originating  in  the  second  and  third  sacral  spinal  nerves, 
or  in  the  rabbit  in  the  third  and  fourth,  and  taking  their  course 
through  the  so-called  nervi  erigentes  or  pelvic  nerves  and  the  hypo- 
gastric  plexus.  Stimulation  of  these  nerves  causes  strong  contrac- 
tions of  the  bladder,  sufficient  to  empty  its  contents.  (3)  Experi- 
ments in  lower  animals  indicate  that  the  urethra,  in  addition 
to  the  paths  just  described,  receives  fibers  also  from  the  pudic 
branch  of  the  sciatic  plexus.  According  to  Nawrocki  and  Skabit- 
schewsky,t  the  spinal  sensory  fibers  from  the  bladder  are  found  in 
the  posterior  roots  of  the  first,  second,  third,  and  fourth  sacral 
spinal  nerves,  particularly  the  second  and  third.  When  these 
fibers  are  stimulated  they  excite  reflexly  the  motor  fibers  to  the 
bladder  found  in  the  anterior  roots  of  the  second  and  third  sacral 
spinal  nerves.  The  relations  of  this  nerve-supply  to  the  act  of 
micturition  is  difficult  to  state.  That  the  act  is  essentially  a  reflex 
through  the  central  nervous  system  is  shown  by  the  fact  that 
section  of  the  nervi  erigentes  or  of  the  posterior  roots  of  the 
sacral  spinal  nerves  abolishes  the  act  and  leads  to  a  distention  of 
the  bladder.  As  far  as  experiments  have  gone  they  indicate  that 
the  motor  path  for  this  reflex  lies  through  the  nervi  erigentes  or 
pelvic  nerves,  while  the  afferent  paths  enter  the  cord  in  the  pos- 
terior roots  of  the  sacral  spinal  nerves,  coming  through  the  pelvic 
or  the  pelvic  and  pudic  nerves.  The  hypogastric  nerve  apparently 
does  not  enter  into  the  reflex,  but  its  inhibitory  influence  upon  the 
bladder  may,  by  relaxing  the  tone  of  the  musculature,  provide  a 
mechanism  for  holding  larger  quantities  of  urine.  So  far  as  the 
bladder  is  concerned  there  is  evidence  that  the  hypogastrics  and 


"Journal  of  Physiology,"  19,  71,  1895. 
"Archiv  f.  die  gesammte  Physiologic," 


KIDNEY    AND    SKIN    AS    EXCRETORY    ORGANS.  867 

pelvic  nerves  are  constantly  in  tonic  action,  one  tending  to  relax 
and  the  other  to  increase  the  tonicity  of  the  bladder  musculature, 
forming  thus  balanced  antagonists.  An  interesting  feature  of  the 
reflex  is  the  part  taken  by  the  internal  sphincter.  During  the 
filling  of  the  bladder  this  sphincter  is  in  tone,  at  the  time  of  empty- 
ing its  tone  presumably  is  inhibited  as  a  part  of  the  reflex  act. 
Experiments  indicate  that  stimulation  of  the  pudic  nerve  causes 
contraction  of  the  sphincter,  while  stimulation  of  the  pelvic  nerve 
causes  relaxation.  It  is  possible,  therefore,  that  in  reflex  mic- 
turition the  pelvic  nerves  carry  the  motor  impulses  that  cause 
contraction  of  the  bladder  musculature  and,  at  the  same  time, 
through  other  fibers,  inhibitory  impulses  that  relax  the  sphincter. 
The  mechanism  is,  however,  complex  and  needs  further  investiga- 
tion.* 

Excretory  Functions  of  the  Skin. — The  physiological  activi- 
ties of  the  skin  are  varied.  It  forms,  in  the  first  place,  a  sensory 
surface  covering  the  body,  and  interposed,  as  it  were,  between  the 
external  world  and  the  inner  mechanism.  Nerve  fibers  of  pressure, 
temperature,  and  pain  are  distributed  over  its  surface,  and  by  means 
of  these  fibers  reflexes  of  various  kinds  are  effected  which  keep  the 
body  adapted  to  changes  in  its  environment.  The  physiology  of 
the  skin  from  this  standpoint  is  discussed  in  the  section  on  special 
senses.  Again,  the  skin  plays  a  part  of  immense  value  to  the  body 
in  regulating  the  body  temperature.  This  regulation,  which  is 
effected  by  variations  in  the  blood  supply  or  the  sweat  secretion, 
is  described  at  appropriate  places  in  the  sections  on  Nutrition  and 
Circulation.  In  the  female,  during  the  period  of  lactation,  the  mam- 
mary glands,  which  must  be  reckoned  among  the  organs  of  the 
skin,  form  an  important  secretion,  the  milk;  the  physiology  of  this 
gland  is  referred  to  in  the  section  on  Reproduction.  In  this  section 
we  are  concerned  with  the  physiology  of  the  skin  from  a  different 
standpoint, — namely,  as  an  excretory  organ.  The  excretions  of 
the  skin  are  formed  in  the  sweat-glands  and  the  sebaceous  glands. 

Sweat. — The  sweat  or  perspiration  is  a  secretion  of  the  sweat 
glands.  These  latter  structures  are  found  over  the  entire  cutaneous 
surface  except  in  the  deeper  portions  of  the  external  auditory  meatus, 
the  prepuce,  and  the  glans  penis.  They  are  particularly  abundant 
upon  the  palms  of  the  hands  and  the  soles  of  the  feet.  Krause 
estimates  that  their  total  number  for  the  whole  cutaneous  surface 
is  about  two  millions.  In  man  they  are  formed  on  the  type  of 
simple  tubular  glands;  the  terminal  portion  contains  the  secretory 
cells,  and  at  this  part  the  tube  is  usually  coiled  to  make  a  more  or 

*  Consult  Barrington,  "Quarterly  Journal  of  Exper.  Physiology,"  8,  33, 
1914;  Elliot,  "Journal  of  Physiology,"  35,  367,  1907;  Stewart,  "American 
Journal  of  Physiology,"  2,  182,  1899. 


868  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

less  compact  knot,  thus  increasing  the  extent  of  the  secreting  sur- 
face. The  larger  ducts  have  a  thin,  muscular  coat  of  involuntary 
tissue  that  may  possibly  be  concerned  in  the  ejection  of  the  secre- 
tion. The  secretory  cells  in  the  terminal  portion  are  columnar  in 
shape,  possess  a  granular  cytoplasm,  and  are  arranged  in  a  single 
layer.  The  amount  of  secretion  formed  by  these  glands  varies 
greatly,  being  influenced  by  the  condition  of  the  atmosphere  as  re- 
gards temperature  and  moisture,  as  well  as  by  various  physical  and 
psychical  states,  such  as  exercise  and  emotions.  The  average  quan- 
tity for  twenty-four  hours  is  said  to  vary  between  700  and  900  gms., 
although  this  amount  may  be  doubled  under  certain  conditions. 

According  to  an  interesting  paper  by  Schierbeck,*  the  average 
quantity  of  sweat  in  twenty-four  hours  may  amount  to  2  to  3  liters 
in  a  person  clothed,  and  therefore  with  an  average  temperature 
of  32°  C.  surrounding  the  skin.  This  author  states  that  the  amount 
of  sweat  given  off  from  the  skin  in  the  form  of  insensible  perspira- 
tion increases  proportionately  with  the  temperature  until  a  certain 
critical  point  is  reached  (about  33°  C.  in  the  person  investigated) , 
when  there  is  a  marked  increase  in  the  water  eliminated,  the  in- 
crease being  simultaneous  with  the  formation  of  visible  sweat.  At 
the  same  time  there  is  a  sudden  increase  in  the  C02  eliminated  from 
the  skin.  It  is  possible  that  the  sudden  increase  in  CO2  is  an  in- 
dication of  greater  metabolism  in  the  sweat  glands  in  connection 
with  the  formation  of  visible  sweat. 

Composition  of  the  Secretion. — The  precise  chemical  composition 
of  sweat  is.  difficult  to  determine,  owing  to  the  fact  that  as  usually 
obtained  it  is  liable  to  be  mixed  with  the  sebaceous  secretion.  Nor- 
mally it  is  a  very  thin  secretion  of  low  specific  gravity  (1.004)  and 
an  alkaline  reaction,  although  when  first  secreted  the  reaction  may 
be  acid  owing  to  admixture  with  the  sebaceous  material.  The 
larger  part  of  the  inorganic  salts  consists  of  sodium  chlorid.  Small 
quantities  of  the  alkaline  sulphates  and  phosphates  are  also  pres- 
ent. The  organic  constituents,  though  present  in  mere  traces,  are 
quite  varied  in  number.  Urea,  uric  acid,  creatinin,  aromatic  oxy- 
acids,  ethereal  sulphates  of  phenol  and  skatol,  serin  (oxyaminopro- 
pionic  acid),  and  albumin,  are  said  to  occur  when  the  sweating  is 
profuse.  Argutinsky  has  shown  that  after  the  action  of  vapor 
baths,  and  as  the  result  of  muscular  work,  the  amount  of  urea 
eliminated  in  this  secretion  may  be  considerable.  Under  patho- 
logical conditions  involving  a  diminished  elimination  of  urea  through 
the  kidneys  it  has  been  observed  that  the  amount  found  in  the 
sweat  is  markedly  increased,  so  that  crystals  of  it  may  be  deposited 
upon  the  skin.  Under  perfectly  normal  conditions,  however,  it 

*"Archiv  f.   Physiologic,"  1893,   116;  see  also  Willebrand,  "Skandi- 
navisehes  Archiv  f.  Physiologic,"  13,  337,  1902. 


KIDNEY    AND    SKIN    AS    EXCRETORY    ORGANS.  869 

is  obvious  that  the  organic  constituents  are  of  minor  importance. 
The  main  fact  to  be  considered  in  the  secretion  of  sweat  is  the  form- 
ation of  water. 

Secretory  Fibers  to  the  Sweat  Glands. — Definite  experimental 
proof  of  the  existence  of  sweat  nerves  was  first  obtained  by  Goltz  * 
in  some  experiments  upon  stimulation  of  the  sciatic  nerve  in  cats. 
In  the  cat  and  dog,  in  which  sweat  glands  occur  on  the  balls  of  the 
feet,  the  presence  of  sweat  nerves  may  be  demonstrated  with  great 
ease.  Electrical  stimulation  of  the  peripheral  end  of  the  divided 
sciatic  nerve,  if  sufficiently  strong,  will  cause  visible  drops  of  sweat 
to  form  on  the  hairless  skin  of  the  balls  of  the  feet.  When  the 
electrodes  are  kept  at  the  same  spot  on  the  nerve  and  the  stimula- 
tion is  maintained  the  secretion  soon  ceases;  but  this  effect  seems 
to  be  due  to  a  temporary  injury  of  some  kind  to  the  nerve  fibers 
at  the  point  of  stimulation,  and  not  to  a  genuine  fatigue  of  the 
sweat  glands  or  the  sweat  fibers,  since  moving  the  electrodes  to  a 
new  point  on  the  nerve  farther  toward  the  periphery  calls  forth  a 
new  secretion.  The  secretion  so  formed  is  thin  and  limpid,  and 
has  an  alkaline  reaction.  The  anatomical  course  of  these  fibers 
has  been  worked  out  in  the  cat  with  great  care  by  Langley.  f  He 
finds  that  for  the  hind  feet  they  leave  the  spinal  cord  chiefly  in  the 
first  and  second  lumbar  nerves,  enter  the  sympathetic  chain,  and 
emerge  from  this  as  pos^ganglionic  fibers  in  the  gray  rami  which 
pass  from  the  sixth  lumbar  to  the  second  sacral  ganglion,  but  chiefly 
in  the  seventh  lumbar  and  first  sacral,  and  then  join  the  nerves  of 
the  sciatic  plexus.  For  the  forefeet  the  fibers  leave  the  spinal  cord 
in  the  fourth  to  the  tenth  thoracic  nerves,  enter  the  sympathetic 
chain,  pass  upward  to  the  first  thoracic  ganglion,  whence  they  are 
continued  as  postganglionic  fibers  that  pass  out  of  this  ganglion  by 
the  gray  rami  communicating  with  the  nerves  forming  the  brachial 
plexus.  The  action  of  the  nerve  fibers  upon  the  sweat  glands  can 
not  be  explained  as  an  indirect  effect, — for  instance,  as  a  result  of 
a  variation  in  the  blood-flow.  Experiments  have  repeatedly  shown 
that,  in  the  cat,  stimulation  of  the  sciatic  still  calls  forth  a  secre- 
tion after  the  blood  has  been  shut  off  from  the  leg  by  ligation  of 
the  aorta,  or  indeed  after  the  leg  has  been  amputated  for  as  long 
as  twenty  minutes.  So  in  human  beings  it  is  known  that  profuse 
sweating  may  often  accompany  a  pallid  skin,  as  in  terror  or 
nausea,  while,  on  the  other  hand,  the  flushed  skin  of  fever  is  char- 
acterized by  the  absence  of  perspiration.  There  seems  to  be  no 
doubt  that  the  sweat  nerves  are  genuine  secretory  fibers,  causing 
a  secretion  in  consequence  of  a  direct  action  on  the  cells  of  the  sweat 
glands.  In  accordance  with  this  physiological  fact  histological 

*  "Archiv  f.  die  gesammte  Physiologic,"  11,  71,  1875. 
t  "Journal  of  Physiology,"  21,  347, 1891. 


870  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

work  has  demonstrated  that  special  nerve  fibers  are  supplied  to 
the  glandular  epithelium.  According  to  Arnstein,  the  terminal 
fibers  form  a  small,  branching,  varicose  ending  in  contact  with  the 
epithelial  cells.  The  sweat  gland  may  be  made  to  secrete  in  many 
ways  other  than  by  direct  artificial  excitation  of  the  sweat  fibers, — 
for  example,  by  external  heat,  dyspnea,  muscular  exercise,  strong 
emotions,  and  by  the  action  of  various  drugs,  such  as  pilocarpin, 
muscarin,  strychnin,  nicotin,  picrotoxin,  and  physostigmin.  In  all 
such  cases  the  effect  is  supposed  to  result  from  an  action  on  the 
sweat  fibers,  either  directly  on  their  terminations  or  indirectly  upon 
their  cells  of  origin  in  the  central  nervous  system.  In  ordinary 
life  the  usual  cause  of  profuse  sweating  is  a  high  external  temper- 
ature or  muscular  exercise.  With  regard  to  the  former  it  is  known 
that  the  high  temperature  does  not  excite  the  sweat  glands  im- 
mediately, but  through  the  intervention  of  the  central  nervous 
system.  If  the  nerves  going  to  a  limb  be  cut,  exposure  of  that 
limb  to  a  high  temperature  does  not  cause  a  secretion,  showing 
that  the  temperature  change  alone  is  not  sufficient  to  excite  the 
gland  or  its  terminal  nerve  fibers.  We  must  suppose,  therefore, 
that  the  high  temperature  acts  upon  the  sensory  cutaneous  nerves, 
possibly  the  heat  fibers,  and  reflexly  stimulates  the  sweat  fibers. 
This  reflex  response  constitutes  a  very  important  means  of  regulat- 
ing the  body  temperature  (see  p.  968),  especially  when  the  external 
temperature  is  high.  Under  the  last  named  condition  the  loss  of 
heat  from  the  body  by  radiation  is  greatly  reduced,  but  the 
secretion  of  sweat,  by  virture  of  the  heat  absorbed  in  its  vaporiza- 
tion, serves  to  augment  this  loss  of  heat  from  the  body  in  propor- 
tion to  the  quantity  of  sweat  formed  and  in  inverse  relation  to  the 
humidity  of  the  surrounding  air.  Although  external  temperature 
does  not  directly  excite  the  glands,  it  should  be  stated  that  it 
affects  their  irritability  either  by  direct  action  on  the  gland  cells 
or  upon  the  terminal  nerve  fibers.  At  a  sufficiently  low  temperature 
the  cat's  paw  does  not  secrete  at  all,  and  the  irritability  of  the  glands 
is  increased  by  a  rise  of  temperature  up  to  about  45°  C. 

Dyspnea,  muscular  exercise,  emotions,  and  many  drugs  affect 
the  secretion,  probably  by  action  on  the  nerve  centers.  Pilocarpin, 
on  the  contrary,  is  supposed  to  stimulate  the  endings  of  the  nerve- 
fibers  in  the  glands,  while  atropin  has  the  opposite  effect,  com- 
pletely paralyzing  the  secretory  fibers. 

Sweat  Centers  in  the  Central  Nervous  System. — The  fact  that 
secretion  of  sweat  may  be  occasioned  by  stimulation  of  afferent 
nerves  or  by  direct  action  upon  the  central  nervous  system,  as  in 
the  case  of  dyspnea,  implies  the  existence  of  physiological  centers 
controlling  the  secretory  fibers.  The  precise  location  of  the  sweat 
center  or  centers  has  not,  however,  been  satisfactorily  determined. 


KIDNEY    AND    SKIN    AS    EXCRETORY    ORGANS.  871 

Histologically  and  anatomically  the  arrangement  of  the  sweat 
fibers  resembles  that  of  the  vasoconstrictor  fibers,  and,  reasoning 
from  analogy,  one  might  suppose  the  existence  of  a  general  sweat 
center  in  the  medulla  comparable  to  the  vasoconstrictor  center, 
but  positive  evidence  of  the  existence  of  such  an  arrangement  is 
lacking.  It  has  been  shown  that  when  the  medulla  is  separated 
from  the  cord  by  a  section  in  the  cervical  or  thoracic  region  the 
action  of  dyspnea,  or  of  various  sudorific  drugs  supposed  to  act  on 
the  central  nervous  system,  may  still  cause  a  secretion.  On  the 
evidence  of  results  of  this  character  it  is  assumed  that  there  are  spinal 
sweat  centers;  but  whether  these  are  few  in  number  or  represent- 
simply  the  various  nuclei  of  origin  of  the  fibers  to  different  regions 
is  not  definitely  known;  It  is  possible  that  in  addition  to  these 
spinal  centers  there  is  a  general  regulating  center  in  the  medulla. 
Sebaceous  Secretion. — The  sebaceous  glands  are  simple  or 
compound  alveolar  glands  found  over  the  cutaneous  surface,  usually 
in  association  with  the  hairs,  although  in  some  cases  they  occur 
separately,  as,  for  instance,  on  the  prepuce  and  glans  penis,  and 
on  the  lips.  When  they  occur  with  the  hairs  the  short  duct  opens 
into  the  hair  follicle,  so  that  the  secretion  is  passed  out  upon  the 
hair  near  the  point  at  which  it  projects  from  the  skin.  The  alveoli  are 
filled  with  cuboidal  or  polygonal  epithelial  cells,  which  are  arranged 
in  several  layers.  Those  nearest  the  lumen  of  the  gland  are  filled 
with  fatty  material.  These  cells  are  supposed  to  be  cast  off  bodily, 
their  detritus  going  to  form  the  secretion.  New  cells  are  formed 
from  the  layer  nearest  the  basement  membrane,  and  thus  the  glands 
continue  to  produce  a  slow  but  continuous  secretion.  The  sebaceous 
secretion,  or  sebum,  is  an  oily,  semiliquid  material  that  sets,  upon 
exposure  to  the  air,  to  a  cheesy  mass,  as  is  seen  in  the  comedones 
or  pimples  which  so  frequently  occur  upon  the  skin  from  occlusion 
of  the  opening  of  the  ducts.  The  exact  composition  of  the  secretion 
is  not  known.  It  contains  fats  and  soaps,  some  cholesterin,  albu- 
minous material  (part  of  which  is  a  nucleo-albumin  often  described 
as  a  casein),  remnants  of  epithelial  cells,  and  inorganic  salts.  The 
cholesterin  occurs  in  combination  with  a  fatty  acid,  and  is  found  in 
especially  large  quantities  hi  sheep's  wool,  from  which  it  is  extracted 
and  used  commercially  under  the  name  of  lanolin.  The  sebaceous 
secretion  from  different  places,  or  in  different  animals,  is  probably 
somewhat  variable  hi  composition  as  well  as  in  quantity.  The 
secretion  of  the  prepuce  is  known  as  the  smegma  prceputii;  that  of 
the  external  auditory  meatus,  mixed  with  the  secretion  of  the  neigh- 
boring sweat  glands  or  ceruminous  glands,  forms  the  well-known 
earwax  or  cerumen.  The  secretion  in  this  place  contains  a  reddish 
pigment  of  a  bitterish-sweet  taste,  the  composition  of  which  has 
not  been  investigated.  Upon  the  skin  of  the  newly  born  the  se- 


872  PHYSIOLOGY    OF    DIGESTION   AND    SECRETION. 

baceous  material  is  accumulated  to  form  the  vernix  caseosa.  The 
well-known  uropygal  gland  of  birds  is  homologous  with  the  mam- 
malian sebaceous  glands,  and  its  secretion  has  been  obtained  in 
sufficient  quantities  for  chemical  analysis.  Physiologically  it  is 
believed  that  the  sebaceous  secretion  affords  a  protection  to  the 
skin  and  hairs.  Its  oily  character  doubtless  serves  to  protect  the 
hairs  from  becoming  too  brittle,  or,  on  the  other  hand,  from  being 
too  easily  saturated  with  external  moisture.  In  this  way  it  prob- 
ably aids  in  making  the  hairy  coat  a  more  perfect  protection  against 
the  effect  of  external  changes  of  temperature.  Upon  the  surface  of 
the  skin,  also,  it  forms  a  thin,  protective  layer  that  tends  to  prevent 
undue  loss  of  heat  from  evaporation  of  the  sweat  and  possibly  is 
important  in  other  ways  in  maintaining  the  physiological  integrity 
of  the  external  surface. 

Excretion  of  C02. — In  some  of  the  lower  animals — the  frog, 
for  example — the  skin  takes  an  important  part  in  the  respiratory 
exchanges,  eliminating  CO2  and  absorbing  O.  In  man,  and  pre- 
sumably in  the  mammalia  generally,  it  has  been  ascertained  that 
changes  of  this  kind  are  very  slight.  Estimates  of  the  amount  of 
CO  2  given  off  from  the  skin  of  man  during  twenty-four  hours  vary 
greatly,  but  the  amount  is  small,  about  7  to  8  gms.  in  twenty-four 
hours,  unless  there  is  marked  sweating,  in  which  case  the  amount  is 
noticeably  increased, 


CHAPTER  XLVL 

SECRETION    OF  THE    DUCTLESS    GLANDS-INTERNAL 

SECRETION, 

The  term  "internal  secretion"  is  used  to  designate  those  secre- 
tions of  glandular  tissues  which,  instead  of  being  carried  off  to  the 
exterior  by  a  duct,  are  eliminated  in  the  blood  or  lymph.  The  idea 
that  secretory  products  may  be  given  off  in  this  way  has  long  been 
held  in  reference  to  the  ductless  glands,  such  as  the  thyroid,  pitui- 
tary body,  etc.,  the  absence  of  a  duct  suggesting  naturally  such  a 
possibility.  The  term,  however,  seems  to  have  been  employed 
first  by  Claude  Bernard,  who  emphasized  the  distinction  between 
the  ordinary  secretions,  or  external  secretions,  and  this  group  of 
internal  secretions.  Modern  interest  in  the  latter  is  due  largely  to 
work  done  by  Brown-Sequard  (1889)  upon  testicular  extracts,  work 
which  itself  was  of  doubtful  value.  This  author  was  led  to  amplify 
the  conception  of  an  internal  secretion  by  the  assumption  that  all 
tissues  give  off  a  something  to  the  blood  which  is  characteristic, 
and  is  of  importance  in  general  nutrition.  This  idea  led  in  turn  to 
a  revival  of  some  old  notions  regarding  the  treatment  of  diseases 
of  the  different  organs  by  extracts  of  the  corresponding  tissue, 
a  therapeutical  method  usually  designated  as  opotherapy.  Brown- 
Sequard's  extension  of  the  idea  of  internal  secretion  has  not  been 
justified  by  subsequent  work,  and  to-day  we  must  limit  the  term 
to  tissues  that  have  a  glandular  structure.  Experience  has  shown, 
that  not  only  the  ductless  glands,  but  some  at  least  of  the  typical 
glands  provided  with  ducts  may  give  rise  to  internal  secretions, 
the  pancreas,  for  example.  The  work  done  since  1889  has  demon- 
strated fully  that  some,  perhaps  all,  of  the  the  ductless  glands  play 
a  role  of  the  very  greatest  importance  in  general  nutrition.  They 
yield  internal  secretions  of  one  kind  or  another,  and  modern  inves- 
tigations have  demonstrated  that  there  is  a  complicated  interrela- 
tion among  the  secretions  as  regards  their  action  on  body  metabo- 
lism. In  view  of  these  facts,  the  entire  group  of  ductless  glands  or  of 
glands  furnishing  definite  internal  secretions  is  sometimes  united 
under  the  designation  of  the  endocrin  system  (endon,  within,  krino, 
I  separate).  The  conception  that  certain  glandular  organs  may 
give  rise  to  chemical  products  which  on  entering  the  circulation 
influence  the  activity  of  one  or  more  other  organs  has  recently 

873 


874  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

found  a  fruitful  application  in  the  study  of  the  digestive  secretions. 
The  gastric  and  pancreatic  secretins  may  be  regarded  as  examples 
of  internal  secretions.  Chemical  products  of  this  kind  which 
stimulate  the  activity  of  special  organs  Starling  designates  as 
hormones*  From  this  point  of  view  the  active  substances  formed 
in  the  thyroids,  adrenal  glands,  etc.,  may  all  be  classified  as  specific 
hormones.  Starling  suggests  that  this  means  of  coordinating  the 
activities  of  the  various  parts  of  a  complex  organism  may  be 
regarded  as  the  most  primitive,  while  the  better-known  coordina- 
tion through  the  medium  of  a  nervous  system  is  of  later  develop- 
ment. In  the  mammalian  body  both  methods,  as  we  have  seen, 
are  employed. 

Schafer  calls  attention  to  the  fact  that  some  hormones  inhibit  functional 
activity  while  others  act  as  a  chemical  stimulant.  The  term  "hormone" 
(hormao,  I  excite),  etymologically  considered,  is  not  applicable  to  the  former 
class.  He  suggests,  therefore,  the  general  term  "autacoid  substances"  for  both 
groups  to  indicate  their  drug-like  action  (acos,  a  remedy),  and  subdivides 
them  into  two  groups  according  as  they  stimulate  or  inhibit. 

\,,4   *~j  O,,KO*  (Hormones — stimulating  action. 

Autacoid  substances  {  Chalones-inhibitory  action. 

Liver. — We  do  not  usually  regard  the  liver  as  furnishing  an 
internal  secretion.  As  a  matter  of  fact,  it  does  form  two  products 
within  its  cells — glycogen  (sugar)  and  urea — which  are  subsequently 
given  off  to  the  blood  for  purposes  of  general  nutrition  or  for  elim- 
ination. The  processes  in  this  case  fall  under  the  general  defini- 
tion of  internal  secretion,  and,  in  fact,  may  be  used  to  illustrate 
specifically  the  meaning  of  this  term.  The  history  of  glycogen  and 
urea  has  been  considered. 

Internal  Secretion  of  the  Thyroid  Tissues. — The  most  im- 
portant and  definite  outcome  of  the  work  on  internal  secretions  has 
been  obtained  with  the  thyroids.  Recent  experimental  work  on 
this  organ  makes  it  necessary  for  us  now  to  distinguish  between  the 
thyroid  and  the  parathyroid  tissues.  The  thyroids  proper  form 
two  oval  bodies  lying  on  the  sides  of  the  trachea  at  its  junction  with 
the  larynx.  They  have  no  ducts,  and  are  composed  of  vesicles  of 
different  sizes,  which  are  lined  by  a  single  layer  of  cuboidal  epithe- 
lium and  contain  in  their  interior  a  material  known  as  colloid.  A 
number  of  histologists  have  traced  the  formation  of  this  colloid  to 
the  lining  epithelial  cells,  and  have  stated,  moreover,  that  the  vesicles 
finally  rupture  and  discharge  the  colloid  into  the  surrounding  lym- 
phatic spaces.  Accessory  thyroids  varying  in  size  and  number  may 
be  found  along  the  trachea  as  far  down  as  the  heart.  They  possess 
a  vesicular  structure  and  no  doubt  have  a  function  similar  to  that 
of  the  thyroid  body. 

*  For  general  discussion,  consult  Starling,  "Recent  Advances  in  the 
Physiology  of  Digestion,"  Chicago,  1906. 


SECRETION  OF  THE  DUCTLESS  GLANDS.          875 

The  parathyroids  are,  according  to  most  authors,  quite  different 
structures.  Four  of  these  bodies  are  usually  described,  two  on  each 
side,  and  their  positions  vary  somewhat  in  different  animals  or, 
indeed,  in  different  individuals.*  In  man  the  superior  (or  internal) 
parathyroids  are  found  upon  the  posterior  surface  of  the  thyroid, 
at  the  level  of  the  junction  of  its  upper  with  its  middle  third.  They 
may  be  imbedded  in  the  thyroid  tissue.  The  inferior  (or  external) 
parathyroids  lie  near  the  lower  margin  of  the  thyroid  on  its  poster- 
ior surface  and  in  some  cases  lower  down  on  the  sides  of  the  trachea. 
The  tissue  has  a  structure  quite  different  from  that  of  the  thy- 
roids, being  composed  of  solid  masses  or  columns  of  epithelial 
cells  which  are  not  arranged  in  vesicles  and  contain  no  colloid. 

Extirpation  of  the  Thyroids  and  Parathyroids. — In  1856 
Schiff  showed  that  extirpation  of  the  thyroids  (and  parathyroids)  in 
dogs  is  followed  by  the  death  of  the  animal  in  one  to  four  weeks. 
The  animal  exhibits  certain  characteristic  symptoms,  such  as 
muscular  tremors,  which  may  pass  into  convulsions,  cachexia, 
emaciation,  and  a  condition  of  apathy  This  result  was  con- 
firmed by  subsequent  observers,  but  many  exceptions  were  noted. 
Great  interest  was  shown  in  these  results,  because  on  the  surgical 
side  reports  were  made  showing  that  after  complete  removal  of  the 
thyroids  in  cases  of  goiter  evil  consequences  might  ensue,  either 
acute  convulsive  attacks  or  chronic  malnutrition.  On  the  other 
hand,  it  became  known  that  atrophy  of  the  thyroids  in  the  young 
is  responsible  for  the  condition  of  arrested  growth  and  deficient 
mental  development  designated  as  cretinism,  and  in  the  adult  the 
same  cause  gives  rise  to  the  peculiar  disease  of  myxedema,  character- 
ized by  distressing  mental  deterioration,  an  edematous  condition 
of  the  skin,  loss  of  hair,  etc.  Schiff  and  others  found  that  the  evil 
results  of  complete  thyroidectomy  in  dogs  might  be  obviated  by 
grafting  pieces  of  the  thyroid  in  the  body,  and  this  knowledge  was 
quickly  applied  to  human  beings  in  cases  of  myxedema  and  cretinism 
with  astonishingly  successful  results.  Instead  of  grafting  thyroid 
tissue  it  was  found,  in  fact,  that  injection  of  extracts  under  the 
skin  or  better  still  simple  feeding  of  thyroid  material  gave  similar 
favorable  results:  the  individuals  recovered  their  normal  appear- 
ance and  mental  powers.!  It  is  stated  that  in  cases  of  myxedema 
the  patient  maybe  kept  in  perfect  health  by  the  administration  of  as 

*  Thompson,  "Philosophical  Transactions,  Roy.  Soc.,"  London,  B.  201 
91,  1910. 

t  For  a  general  account  of  the  development  of  the  subject  and  the  liter- 
ature see  "Transactions  of  the  Congress  of  American  Physicians  and  Sur- 
§eons"  (Howell,  Chittenden,  Adami,  Putnam,  Kinnicutt,  Osier),  1897;  Jean- 
elize,  "Insuffisance  thyroidienne  et  parathyroidienne,"  Nancy,  1902;  Vincent, 
"Internal  Secretions,"  etc.,  Lancet,  Aug.  11  and  18,  1906;  also  "Ergebnisse  der 
Physiologic,"  11,  1911;  Biedl,  "Innere  Sekretion,"  Berlin,  1913. 


876  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

little  as  60  to  130  mgm.  every  three  or  four  days.  Later  Baumann  * 
succeeding  in  isolating  from  the  glands  a  substance  designated  as 
iodothyrin  or  thyroiodin,  which  shows  in  large  measure  the  beneficial 
influence  exerted  by  thyroid  extracts  in  cases  of  myxedema  and 
parenchymatous  goiter.  This  substance  is  characterized  by  con- 
taining a  large -amount  of  iodin  (9.3  per  cent,  of  the  dry  weight). 
It  is  contained  in  the  gland  in  combination  with  protein  bodies, 
from  which  it  may  be  separated  by  digestion  with  gastric  juice  or 
by  boiling  with  acids. 

The  Function  of  the  Parathyroids. — Most  of  the  results  des- 
cribed above  were  obtained  before  the  existence  of  the  parathy- 
roids was  recognized.  Early  in  the  history  of  the  subject  it  was 
discovered  that  complete  removal  of  the  thyroids  proper  in  herbiv- 
orous animals  (rats,  rabbits)  is  not  attended  by  a  fatal  result. 
Gley  and  others,  however,  proved  that  if  the  parathyroids  also  are 
removed  these  animals  die  with  the  symptoms  described  in  the 
case  of  dogs,  cats,  and  other  carnivorous  animals.  This  result 
attracted  attention  to  the  parathyroids.  Numerous  experiments 
by  Moussu,  Gley,  Vassale  and  Generale,  and  others  have  seemed 
to  show  a  marked  difference  between  the  results  of  thyroi- 
dectomy  and  parathyroidectomy.  When  the  parathyroids  alone  are 
removed  the  animal  dies  quickly  with  acute  symptoms,  muscular 
convulsions  (tetany),  etc.;  when  the  thyroids  alone  are  removed 
the  animal  may  survive  for  a  long  period,  but  develops  a  condition 
of  chronic  malnutrition, — a  slowly  increasing  cachexia  which  may 
exhibit  itself  in  a  condition  resembling  myxedema  in  man.  This 
distinction  has  been  generally  accepted,  and  it  throws  much  light 
upon  the  discrepancy  in  the  results  obtained  by  some  of  the  earlier 
observers.  Complete  thyroidectomy  with  the  acutely  fatal  results 
usually  described  includes  those  cases  in  which  both  thyroids  and 
parathyroids  were  removed,  while  probably  many  of  the  apparently 
negative  results  obtained  after  excision  of  the  thyroids  are  expli- 
cable on  the  supposition  that  one  or  more  of  the  parathyroids  were 
left  in  the  animal.  It  should  be  stated,  however,  that  two  recent 
observers,  Vincent  and  Jolly,  as  the  result  of  numerous  experi- 
ments made  upon  different  varieties  of  animals,  throw  some  doubt 
upon  these  conclusions.  They  contend  that  in  herbivorous  animals 
fully  half  of  those  operated  upon  survive  complete  removal  of  all 
thyroid  tissue,  showing  no  evil  symptoms  except  perhaps  a  di- 
minished resistance  to  infection.  Carnivorous  animals,  on  the  con- 
trary, usually  die  after  such  an  operation.!  In  spite  of  such  con- 
tradictory results  in  the  hands  of  some  observers  the  general  opinion 


1910. 


'  "Zeitschrift  f.  physiolog.  Chemie,"  21,  319,  and  481,  1896. 

t  See  also  Halpenny  in   "Surgery,  Gynecology,  and  Obstetrics,"  May, 


SECRETION    OF    TEE    DUCTLESS    GLANDS.  877 

prevails  that  complete  removal  of  the  parathyroids  is  followed  by 
acutely  toxic  results  which  develop  rapidly,  and  the  most  common 
symptom  of  which  is  muscular  tetany.  This  tetany  exhibits 
itself  as  fibrillar  contractions  of  the  muscles,  a  general  muscular 
tremor,  tonic  and  clonic  spasms  of  the  muscles  or  "  intention 
spasms,"  that  is,  spasmodic  or  uncoordinated  contractions  follow- 
ing upon  an  effort  to  make  a  voluntary  movement  *  As  is  well 
known,  similar  symptoms  are  often  observed  under  other  condi- 
tions, infantile  tetany,  gastro-intestinal  tetany,  etc.,  and  it  has 
been  suggested  that  in  all  such  cases  the  initial  difficulty  may 
consist  in  the  insufficiency  of  active  parathyroid  tissue.  Several 
observers  have  reported  that  injections  of  extract  of  the  parathy- 
roids cause  the  tetany  to  disappear  without,  however,  protecting 
the  animal  from  a  fatal  outcome.  Macallum  and  Voegtlinf 
find  that  injection  or  ingestion  of  solutions  of  calcium  salts  removes 
completely  the  symptoms  of  tetany  and  restores  the  animal  to 
an  apparently  normal  condition.  They  have  obtained  similar 
results  upon  human  beings  suffering  from  tetany  as  a  result  of 
unintentional  removal  of  the  parathyroids.  The  experimental 
evidence  in  the  case  of  the  parathyroids  tends  to  support  the 
view  that  their  function  consists  in  neutralizing  in  some  way 
toxic  substances  formed  elsewhere  in  the  body,  and  that,  therefore, 
after  removal  of  these  glands  death  occurs  from  the  accumulation 
of  such  toxic  bodies  in  the  blood  and  tissues.  Thus  Macallum 
states  that  in  animals  in  which  tetany  has  developed  as  a  conse- 
quence of  extirpation  of  the  parathyroids,  bleeding  and  infusion 
of  salt  solution  causes  the  tetany  to  disappear,  a  result  which  may 
be  explained  by  supposing  that  some  toxic  substance  has  been 
removed.  One  specific  hypothesis  along  this  line  has  been  suggested 
by  Patont  and  his  co-workers.  They  found  that  the  symptoms 
observed  after  extirpation  of  the  parathyroids  may  be  produced 
also  by  injections  of  salts  of  guanidin,  and  since  after  parathyroid- 
ectomy  there  is  a  marked  increase  of  guanidin  compounds  in  the 
blood  and  urine  they  come  to  the  conclusion  that  the  parathyroids 
are  concerned  in  the  regulation  of  the  metabolism  of  the  guanidin 
compounds  in  the  body.  When  these  bodies  are  removed  the 
guanidin  accumulates  in  the  blood  and  gives  rise  to  the  tetany 
and  fatal  result.  The  view  that  the  parathyroids  are  simply  im- 
mature thyroid  tissue  is  still  supported  by  some  observers,  being 
based  chiefly  on  the  histological  finding  that  after  removal  of  the 
thyroids  the  parathyroids  may  hypertrophy  and  show  thyroid 

*  For  literature  and  summary,  see  Bing,  "Zentralblatt  f.  d.  Physiol.  u. 
Pathol.  d.  Stoffwechsels,"  1908,  Nos.  1  and  2;  also  Biedl,  loc.  cit. 

f  Macallum  and  Voegtlin,  "Johns  Hopkins  Hospital  Bulletin,"  March. 
1908. 

t  Paton,  et.  al,  "Quarterly  Journal  of  Exp.  Physiology,"  1917,  10,  203. 


878  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

cysts  containing  colloidal  material.  Most  observers,  however, 
take  the  view  outlined  above,  that  the  parathyroids  have  a  func- 
tional significance  essentially  different  from  that  of  the  thyroids, 
and  that  the  parathyroids  as  they  exist  in  the  body  are  not  simply 
undeveloped  or  immature  thyroid  tissue. 

The  Function  of  the  Thyroid. — According  to  the  opinion 
of  most  writers  on  the  subject,  removal  of  the  thyroid  alone, 
leaving,  at  least,  the  external  parathyroids  uninjured,  is  followed 
by  the  development  of  a  state  of  chronic  malnutrition  which 
expresses  itself  finally  in  a  condition  of  cachexia.  Following  a 
terminology  sometimes  used  in  medical  literature,  this  cachectic 
condition  maybe  designated  as  "cachexia  thyreopriva,"  whereas 
the  convulsive  condition  or  tetany,  formerly  also  described  as  a 
symptom  of  loss  of  the  thyroid,  is  due  rather  to  removal  of  the 
parathyroid,  and  may  be  characterized  as  "tetania  parathyreo- 
priva."  No  adequate  explanation  has  been  furnished  of  the  in- 
fluence exercised  by  the  thyroid  on  the  nutrition  of  the  body.  It 
is  usually  assumed  that  the  thyroid  cells  form  an  internal  secretion 
containing  a  specific  hormone  which  acts  as  a  chemical  stimulus  to 
other  tissues,  causing  an  augmentation  of  their  metabolism. 
Justification  for  this  view  is  found  in  the  effect  of  feeding  thyroid 
tissue  to  normal  individuals.  The  result  in  such  cases  is  a  marked 
increase  in  the  excretion  of  nitrogen  and  an  augmentation  of  the 
oxidations  of  the  body,  as  shown  by  an  increase  in  the  output  of 
carbon  dioxid.  On  this  basis  the  tissue  has  been  administered  for 
the  purpose  of  reducing  the  body  fat  in  cases  of  adiposity,  but  the 
details  of  its  influence  on  the  metabolic  processes  are  for  the  most 
part  unknown,  and  when  used  beyond  certain  limits  it  may  cause 
heart  effects  and  other  disturbances  of  a  pathological  nature.  More 
striking  results  have  been  obtained  from  calorimetric  observations 
upon  cases  of  exophthalmic  goiter  and  cretinism.  In  the  former 
condition  it  is  supposed  that  there  is  a  hypersecretion  of  the  thyroid 
bodies,  and  Du  Bois*  reports  that  in  such  cases  the  basal  metab- 
olism is  greatly  augmented,  the  increase  amounting  to  75  per  cent, 
or  more  when  reckoned  on  the  basis  of  calories  of  heat  produced  per 
square  meter  of  skin  area.  Expressed  in  this  unit  the  metabolism 
of  a  normal  person  is  39.7  calories  per  square  meter;  that  of  a  case 
of  exophthalmic  goiter  as  much  as  75  calories.  On  the  other  hand, 
in  cretinism  and  in  myxedema,  in  which  there  is  a  reduced  activity 
of  the  thyroid  body,  the  basal  metabolism  is  reduced  below  normal. 
It  would  seem  to  follow  from  these  facts  that  the  internal  secretion 
of  this  gland  must  have  a  profound  and  probably  variable  influence 
on  metabolism.  The  way  in  which  this  influence  is  exerted  and 

*  Du  Bois,  "Archives  of  Internal  Medicine,  17,  915,  1916. 


SECRETION    OF   THE    DUCTLESS  GLANDS.  879 

regulated  remains  to  be  discovered.  Cannon  and  Cattell*  have 
given  some  evidence  to  show  that  the  thyroids  possess  secretory 
nerves  supplied  through  the  sympathetic  autonomies,  and,  on  the 
other  hand,  that  adrenalin  injected  into  the  blood  stimulates  the 
thyroid  to  greater  activity.  In  line  with  this  latter  result  several 
observers  f  report  an  interrelation  in  the  activity  of  the  thyroid 
and  adrenal  bodies.  Thyroid  extracts  or  stimulation  of  the  nerves 
supplying  the  thyroid  gland  greatly  augments  the  effect  of  a  sub- 
sequent injection  of  adrenalin.  According  to  these  results  thyroid 
secretion  increases  the  efficacy  of  adrenalin,  and,  on  the  other  hand, 
adrenalin  augments  the  secretion  of  the  thyroid  hormone.  The 
nature  of  the  thyroid  hormone  has  been  studied  with  success.  As 
was  stated  above,  Baumann  isolated  from  the  thyroid  a  peculiar 
substance,  iodothyrin,  which  is  characterized  chemically  by  a  large 
percentage  of  iodin,  and  physiologically  by  the  fact  that  when  used 
upon  patients  suffering  from  a  deficiency  in  functional  activity  of 
the  thyroid  (myxedema,  goiter)  it  gives  beneficial  results.  Recently 
Kendall  |  has  isolated  from  the  gland  a  simpler  crystalline  com- 
pound containing  iodin  which  possesses  the  physiological  proper- 
ties of  thyroid  extracts.  He  gives  to  this  compound  the  formula 
of  CiiHioOsNIa,  and  designates  it  as  thyro-oxy-indol,  or  thyroxin. 
It  is  stated  by  Kendall  that  this  substance  is  as  efficacious  as 
desiccated  thyroid  in  the  treatment  of  myxedema  and  cretinism. 
There  has  been  much  discussion  regarding  the  iodin  constituent 
of  the  thyroid  tissue.  Extensive  observations  have  shown  that 
in  some  entirely  healthy  animals  iodin  is  absent  or  is  present  only 
in  traces,  and  in  animals  in  which  it  is  present  the  amount  may 
vary  greatly  with  the  character  of  the  food.  Hunt  gives  the  fol- 
lowing table : 

Per  cent,  of  iodin. 

Children's  thyroid none. 

Maltese  kid  thyroid none. 

Guinea-pig  thyroid 0.05 

Dog  thyroid 0.061 

Cat  thyroid 0.08 

Sheep  thyroid 0.176 

Beef  thyroid 0.25 

Hog  thyroid 0.33 

Human  (Wells) 0.236 

Human  (goitre) 0.04 

Opinions  in  regard  to  the  significance  of  the  iodin  have  varied 
from  the  view,  on  the  one  hand,  that  it  is  an  essential  constituent 
of  the  physiologically  active  substance  secreted  by  the  gland,  to 

*  Cannon  and  Cattell,  "American  Journal  of  Physiology,"  41,  pp.  39,  58, 
74, 1916. 

t  Asher,  "Deutsch.  Med.  Wochenschrift,"  34,  1,  1916,  and  Levy,  "Ameri- 
can Journal  of  Physiology,"  41,  492,  1916. 

J  Kendall,  "Jour.  Amer.  Med.  Assoc.,"  66,  811,  1916;  also  "American 
Journal  of  Physiology,"  Proc.  Physiolog.  Soc.,  vol.  45,  No.  4,  1918. 


880  PHYSIOLOGY   OF    DIGESTION    AND    SECRETION. 

the  opposite  extreme  that  it  is  an  injurious  substance  which  is 
bound  and  made  innocuous  by  the  thyroid  cells.  The  balance 
of  evidence  seems  to  favor  the  first  point  of  view.*  The  active 
substance  in  the  thyroid  secretion  is  an  iodin  compound,  the 
efficacy  of  which  is  dependent  not  upon  the  iodin  constituent 
alone,  since  other  organic  iodin  compounds,  iodin-protein  com- 
plexes, for  example,  are  inactive,  but  upon  the  special  form  in 
which  it  is  combined. 

Thymus. — The  physiology  of  the  thymus  gland  is  very  obscure, 
in  fact,  nothing  that  is  definite  can  be  said  about  its  functions,  ex- 
cept perhaps  that  the  gland  is  concerned  in  some  way  with  the 
processes  of  growth.  It  is  assumed  that  it  furnishes  an  internal 
secretion,  and  that  in  early  life  at  least  this  secretion  influences  in  an 
important  way  some  phases  of  the  body  metabolism.  Formerly, 
it  was  supposed  that  the  gland  reaches  its  maximum  size  at  birth 
and  afterward  undergoes  a  process  of  atrophy  or  involution  so  that 
it  is  entirely  absent  in  adult  life.  More  careful  observations  indi- 
cate, on  the  contrary,  that  the  gland  retains  its  size  and  presumably 
its  full  activity  until  the  period  of  puberty.  Thenceforward  it 
does  undergo  a  gradual  atrophy,  but  apparently  throughout  life 
some  remnants  of  the  gland  tissue  persist  embedded  in  fat.  It 
appears  also  that  under  pathological  conditions  there  may  be  a 
persistence  of  more  of  this  tissue  than  is  normal,  or  there  may  be 
a  real  hypertrophy  together  with  an  overactivity,  a  condition 
which  might  be  designated  as  hyperthymusism.  It  is  recognized 
now  that  this  activity  may  be  a  complicating  factor  in  exophthal- 
mic goiter  (Graves'  disease).  The  anatomical  facts  in  regard  to 
the  involution  of  the  gland  after  puberty  justify  the  suggestion 
that  the  function  it  exercises  is  of  especial  importance  in  the  period 
preceding  the  maturation  of  the  sexual  glands,  but  that  in  post- 
pubertal  life  it  continues  to  play  some  r61e,  although  of  subordinate 
importance.  Very  many  experiments  have  been  made  to  deter- 
mine the  nature  of  the  function  of  this  tissue,  but  at  present  it  is 
not  possible  to  interpret  the  results  in  a  satisfactory  manner,  f 
Removal  of  the  gland  in  young  dogs  (Basch)  is  said  to  cause  a 
retarded  growth  of  the  bony  tissues  and  to  induce  a  condition  re- 
sembling rickets.  At  the  same  time  the  peripheral  nervous  sys- 


1910,  and  Kendall,  1916,  loc.  cit. 

t  References:  Friedleben,  "Die  Physiologic  der  Thymusdriise,"  1858: 
Verdun  "Derives  branchiaux  chez  les  vertebres,"  1898;  Henderson,  "Journal 
of  Physiology  "  1904,  xxxi.,  222;  Basch,  "Jahrbuch  f.  Kinderheilkunde,"  64, 
1906,  and  68/1908;  Klose  and  Vogt,  "Klinik  u.  Biologie  d  Thymusdriise  " 
Tubingen  1910;  Halsted,  "Johns  Hopkins  Hospital  Bulletin,"  August,  1914; 
Hart,  "Virchow's  Archiv,"  214,  1,  1913. 


SECRETION   OF   THE    DUCTLESS    GLANDS.  881 

tern  shows  an  increased  excitability  as  determined  by  the  response 
of  the  nerves  to  galvanic  stimulation.  Somewhat  similar  but  more 
extensive  experiments  have  been  reported  by  Klose  and  Vogt. 
When  thymectomy  is  performed  on  quite  young  dogs  (10  days), 
very  serious  consequences  result,  ending  perhaps  in  a  condition  of 
coma  and  death.  These  results  develop  slowly:  there  is  first  a 
stage  of  increased  fat  formation  and  later  one  of  malnutrition  or 
cachexia  which  manifests  itself  strikingly  in  an  atrophic  and 
undeveloped  condition  of  the  bones,  although  there  is  besides  a 
general  asthenic  or  adynamic  condition  and  mental  deterioration. 
Injections  of  extract  of  the  gland  (Svehla)  cause  a  fall  of  blood- 
pressure  and  some  quickening  of  the  heart-beat,  but  these  effects 
are  not  specific.  Unlike  the  thyroid  and  parathyroid  glands,  the 
thymus  contains  no  iodin  (Mendel) .  One  suggestion  made  regard- 
ing its  influence  is  that  there  is  some  sort  of  reciprocal  relationship 
between  it  and  the  reproductive  glands.  Castration  (Henderson) 
causes  a  persistent  growth  and  retarded  atrophy  of  the  thymus, 
while  removal  of  the  thymus  (Paton)  hastens  the  development  of 
the  testes.  Another  more  specific  hypothesis  is  the  one  advo- 
cated by  Klose  and  Vogt  in  the  work  referred  to  above,  namely, 
that  the  thymus  is  concerned  especially  in  the  processes  of  syn- 
thesis of  nucleic  acid. 

Gudernatsch  *  finds  that  young  tadpoles  fed  upon  thymus  gland 
are  stimulated  to  excessive  growth,  while  the  changes  of  meta- 
morphosis to  the  frog-stage  are  correspondingly  delayed.  When 
thyroid  gland  is  fed,  contrary  results  are  obtained.  Further 
growth  is  inhibited  and  the  changes  of  metamorphosis  are  acceler- 
ated, so  that  dwarf  frogs  are  produced.  This  apparently  direct 
proof  that  the  thymus  is  connected  with  growth  falls  in  very  well 
with  what  is  stated  above  in  regard  to  the  importance  of  this 
organ  during  the  prepubertal  period. 

Adrenal  Bodies. — The  adrenal  bodies — or,  as  they  are  frequently 
called  in  human  anatomy,  the  suprarenal  capsules — belong  to  the 
group  of  ductless  glands.  It  was  shown  first  by  Brown-Se*quard 
(1856)  that  removal  of  these  bodies  is  followed  rapidly  by  death. 
This  result  has  been  confirmed  by  many  experimenters,  and  so  far 
as  the  observations  go  the  effect  of  complete  removal  is  the  same 
in  all  animals.  The  fatal  effect  is  more  rapid  than  in  the  case  of 
removal  of  the  thyroids,  death  following  the  operation  usually  in 
two  to  three  days,  or,  according  to  some  accounts,  within  a  few 
hours.  The  symptoms  preceding  death  are  great  prostration,  mus- 
cular weakness,  and  marked  diminution  in  vascular  tone.  These 
symptoms  resemble  those  occurring  in  Addison's  disease  in  man, — 
a  disease  which  clinical  evidence  has  shown  to  be  associated  with 

*  Gudernatsch,  "Zentralblatt  fur  Physiology,"  1912,  No.  7. 
56 


882  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

pathological  lesions  in  the  suprarenal  capsules.  These  older  ob- 
servations indicated  clearly  enough  that  the  adrenal  glands  are  of 
essential  importance  to  the  life  of  the  organism,  but  the  first  precise 
indication  as  to  the  nature  of  its  activity  was  furnished  by  the  dis- 
covery, made  by  Oliver  and  Schafer,*  of  the  remarkable  effects 
observed  when  an  extract  of  the  medulla  of  the  gland  is  injected 
into  the  circulation  of  a  living  animal.  Briefly  stated,  the  effect 
of  such  an  injection  is  a  pronounced  slowing  of  the  heart-beat 
together  with  a  rise  of  pressure.  The  slowing  of  the  heart-beat  is 
due  to  a  stimulation  of  the  cardio-inhibitory  center,  for  if  the 
vagi  are  cut  before  making  the  injection  this  result  drops  out; 
the  blood-pressure,  on  the  contrary,  not  being  restrained  by  the 
slowing  of  the  heart,  rises  rapidly  and  may  reach  an  extraordinary 
height.  The  explanation  of  the  effect  of  the  extracts  on  blood- 
pressure  is  given  below. 

Since  effects  of  this  kind  were  not  obtained  from  extracts  of  the 
cortex  of  the  gland,  it  was  apparent  from  these  initial  experiments 
that  in  the  adrenal,  as  in  the  thyroid  tissue,  there  are  two  organs 
or  tissues  to  be  considered  whose  functions  may  be  very  different. 
Subsequent  investigations  have  served  to  strengthen  this  belief,  f 
The  cortical  and  medullary  tissues  are  separate  anatomically  from 
each  other  in  some  of  the  fishes,  and  embryologically  have  different 
origins.  It  has  been  proposed  to  speak  of  the  cortical  tissue  as  the 
interrenal  system  and  of  the  medulla  as  the  adrenal  or  the  chro- 
ma ffin  or  chromaphil  system,  but  for  our  purpose  it  will  be  simpler 
to  state  briefly  the  main  facts  that  have  been  obtained  under  the 
headings  cortex  and  medulla. 

Physiology  of  the  Medulla. — The  Active  Principle,  Epinephrin. 
— Chemical  investigations  of  the  substance  in  the  medulla  which 
causes  the  inhibition  of  the  heart  and  the  rise  of  blood-pressure 
have  been  very  successful.  The  substance  has  been  prepared  in 
pure  form,  its  chemical  structure  is  known,  and  it  has  been  made 
synthetically  outside  the  body.  J  The  credit  for  the  most  impor- 
tant initial  work  is  due  to  Abel,  while  the  final  isolation  in  pure  form 
as  crystals  was  accomplished  by  Takamine  and  independently  by 
Aldrich.  The  last-named  observer  determined  the  correct  formula 
for  the  active  substance,  namely,  C9Hi3NO3,  and  later  workers 
(Stolz  and  Dakin)  succeeded  in  demonstrating  its  chemical  struc- 
ture as  a  dioxyphenyl — ethylol-methylamin,  C6H3(OH)2CHOH- 
CH2NHCH3.  The  presence  of  the  oxyphenyl  group  in  the  com- 
pound would  suggest  that  in  the  body  it  is  probably  derived  from 

*  Oliver  and  Schafer,  "Journal  of  Physiology,"  18,  230,  1895. 

t  See  Swale  Vincent,  "  Transactions  of  the  American  Gynecological  So- 
ciety, 1917. 

JFor  description  of  chemistry  and  references,  see  Barger,  "The  Simpler 
Natural  Bases"  (Monographs  on  Biochemistry),  1814. 


SECRETION    OF    THE    DUCTLESS   GLANDS.  883 

tyrosin.  This  active  substance  is  designated  in  the  literature 
under  a  variety  of  names,  those  commonly  used  being  epinephrin, 
adrenalin,  and  adrenin.  It  is  a  basic  body  which  gives  a  number  of 
characteristic  color  reactions,  and  in  alkaline  solutions  is  readily 
oxidized  to  a  substance  that  fails  to  exhibit  the  characteristic  epi- 
nephrin reaction  on  heart-rate  and  blood-pressure. 

Distribution  of  the  Epinephrin. — The  Chromaffin  Tissues. — As 
stated  above,  the  epinephrin  occurs  in  the  adrenal  gland  in  the  cells 
of  the  medulla,  but  not  in  those  of  the  cortex.  When  the  medullary 
cells  are  treated  with  chromates  they  give  a  characteristic  yellow 
or  brown  reaction,  which  is  spoken  of  as  a  chromaffin  reaction  and 
has  been  used  to  locate  similar  cells  in  other  tissues.  It  would  seem 
that  cells  of  this  variety  may  be  found  generally  or  frequently  in 
the  sympathetic  ganglia,  so  that  it  has  been  suggested  that  primi- 
tively each  such  ganglion  contained  two  varieties  of  cells,  the  nerve 
cell  or  ganglion  cell  and  the  chromaffin  or  paraganglion  (Elliott) 
cell.  Clumps  or  strings  of  such  cells  occur  also  along  the  course  of 
the  abdominal  aorta  below  the  level  of  the  adrenal  glands,  and,  as 
was  stated  above,  in  some  of  the  fishes  the  medullary  cells  of  the 
adrenal  gland  are  separated  anatomically  from  the  cortical  cells. 
On  account  of  the  color  reaction  and  the  demonstration,  in  some 
cases  at  least,  that  this  color  reaction  indicates  the  presence  of 
epinephrin,  it  has  become  customary  to  group  all  the  cells  exhibit- 
ing the  chromate  reaction  under  the  general  term  of  chromaffin  or 
chromaphil  system*  and  to  suppose  that  all  this  tissue,  wherever 
found,  has  a  common  physiological  significance.  The  medulla  of 
the  adrenal  gland  is  the  most  conspicuous  and  important  group  of 
these  cells,  but  it  is  assumed  that  in  case  of  removal  by  disease  or 
experiment  its  functions  may  be  supplied  more  or  less  perfectly 
by  the  outlying  cells  belonging  to  the  same  tissue. 

Physiological  Action  of  the  Epinephrin. — As  stated  above, 
solutions  of  epinephrin  give  a  marked  effect  upon  the  heart-rate 
and  blood-pressure.  The  great  slowing  of  the  heart-rate  is  due  to 
an  action  of  the  epinephrin  on  the  cardio-inhibitory  center,  since 
it  disappears  when  the  vagi  are  cut  or  after  the  administration  of 
atropin.  When  this  influence  of  the  cardio-inhibitory  center  is 
removed  it  can  be  shown  that  the  epinephrin  causes  a  stronger  and 
more  rapid  contraction  of  the  heart,  and  a  similar  effect  can  be  ob- 
tained upon  the  isolated  heart  maintained  by  an  artificial  circula- 
tion. It  seems  probable  that  this  effect  of  the  epinephrin  is  due  to 
a  stimulating  action  upon  the  endings  of  the  accelerator  nerve  in 
the  heart.  In  addition  to  the  heart  effect  the  epinephrin  causes  a 
strong  contraction  of  the  arterioles  in  certain  areas,  and  experiments 
demonstrate  that  this  effect  is  due  mainly  to  a  peripheral  action.  It 

*  See  Vincent,  "Proceedings  of  the  Royal  Society,"  B,  82,  502,  1910. 


884  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

is  this  action  that  produces  the  great  rise  in  blood-pressure,  seen 
especially  after  the  antagonistic  influence  of  the  cardio-inhibitory 
center  is  thrown  out  by  section  of  the  vagi.  Under  usual  conditions 
this  effect  on  blood-pressure  is  short-lasting.  The  arterial  pres- 
sure after  reaching  a  maximum  falls  off  rapidly  to  normal,  but  a 
new  rise  can  be  produced  by  a  new  injection.  The  effect  of  the 
epinephrin  on  blood-pressure  is  so  constant  and  is  produced  by 
such  small  doses  that  it  may  be  used  quantitatively  in  estimating 
the  amount  of  epinephrin  in  various  extracts.  Investigation  has 
shown  that  not  all  of  the  arterioles  are  stimulated  to  contraction  by 
epinephrin,  and  the  results  of  many  experiments  of  this  kind  have 
led  to  the  generalization  (Langley)  that  the  epinephrin  acts  only 
upon  the  plain  muscle  which  receives  its  innervation  from  the  sym- 
pathetic autonomic  system,  and  that  its  effect  upon  the  muscula- 
ture, whether  of  stimulation  or  of  inhibition,  is  the  same  as  that  ob- 
tained by  direct  stimulation  of  the  sympathetic  nerve-supply.  This 
selective  action  of  the  epinephrin  finds  some  explanation  in  the  hy- 
pothesis that  it  does  not  affect  the  muscular  substance  directly,  but 
acts  upon  a  specialized  receptive  substance,  the  myoneural  junction 
(Elliott)  at  the  point  where  the  sympathetic  nerve-fiber  unites  with 
the  muscle-fiber.  On  the  basis  of  this  generalization,  perfusion  with 
solutions  containing  epinephrin  has  been  used  as  a  method  for 
determining  whether  or  not  the  blood-vessels  of  any  given  organ  are 
supplied  with  vasoconstrictor  nerve-fibers.  These  fibers  all  belong 
to  the  sympathetic  autonomic  system,  and  those  blood-vessels 
which  exhibit  a  contraction  under  the  influence  of  epinephrin  prob- 
ably are  supplied  with  vasoconstrictor  nerve-fibers.  The  use  of  this 
method  is  referred  to  in  connection  with  the  discussion  regarding 
the  presence  or  absence  of  such  nerve-fibers  to  the  arteries  of  the 
brain,  the  lungs,  and  the  heart.  On  the  same  generalization  it  will 
be  noted  that  plain  muscle  receiving  inhibitory  fibers  from  the 
sympathetic  autonomic  system  ought  to  exhibit  a  relaxation  instead 
of  a  contraction  when  acted  upon  by  epinephrin.  This,  in  fact, 
seems  to  be  the  case.  The  plain  muscle  in  the  intestinal  walls 
receives  inhibitory  fibers  from  the  sympathetic  autonomies 
(splanchnics),  and  on  this  musculature  epinephrin  does  cause  loss 
of  tone  and  relaxation  instead  of  contraction,  and  another  beautiful 
example  of  the  same  kind  is  obtained  from  the  iris.  The  dilator 
muscle  of  the  iris  is  supplied  by  nerve-fibers  from  the  sympathetic 
autonomies,  and  in  correspondence  with  this  fact  the  epinephrin  in 
very  minute  doses  causes  a  dilatation  of  the  pupil.  The  blood- 
vessels of  the  heart  and  the  skeletal  muscles*  are  said  to  be  dilated 
by  doses  of  epinephrin  which  would  cause  constriction  in  the  arteries 

*  Hoskins,  Gunning,  and  Berry,  "American  Journal  of  Physiology,"  41, 
513,  1916. 


SECRETION    OF   THE    DUCTLESS    GLANDS.  885 

of  the  skin  or  the  intestine.  In  accordance  with  the  generalization 
that  epinephrin  acts  only  or  mainly  upon  the  endings  of  the  sym- 
pathetic autonomic  fibers,  this  result  is  interpreted  to  mean  that 
the  heart  muscle  and  the  skeletal  muscle  are  supplied  with  vaso- 
dilator fibers.  Stimulation  of  the  endings  of  these  fibers  by  the 
epinephrin  causes  therefore  vascular  inhibition  or  dilatation.  On 
the  plain  muscle  in  other  organs  epinephrin  has  a  somewhat  variable 
effect,  differing  with  conditions  or  with  the  animal  selected.  The 
uterine  musculature,  for  example,  in  the  pregnant  cat  is  made  to 
contract,  but  in  the  non-prgenant  condition  it  shows  relaxation. 
The  plain  muscle  of  the  bronchioles  exhibits  relaxation  under  the  in- 
fluence of  the  epinephrin,  and  since  these  muscles  probably  receive 
their  nerve-supply  through  the  bulbar  autonomies  (vagus)  their  re- 
action to  epinephrin  indicates  that  the  above  generalization  in  re- 
gard to  the  sympathetic  autonomies  must  not  be  understood  to 
mean  that  the  epinephrin  acts  only  on  the  musculature  innervated 
by  the  sympathetics,  but  rather  that  the  muscle  so  innervated 
shows  a  special  response  to  epinephrin  action.  Even  skeletal  mus- 
cles are  distinctly  affected  by  epinephrin.  Under  the  influence  of 
appropriate  doses,  the  contractions  are  increased  in  size  and  the  sub- 
sequent relaxation  seems  to  be  more  rapid  and  complete.  In  addi- 
tion to  its  influence  on  the  muscular  or  neuromuscular  mechanisms 
epinephrin  has  an  effect  upon  the  -body  metabolism,  especially  as 
regards  the  carbohydrates.  When  injected  it  causes  an  output  of 
sugar  in  the  urine,  which  may  last  for  some  days.  Evidently  the 
epinephrin,  in  these  overdoses,  interferes  in  some  way  with  the 
sugar-regulating  mechanism  of  the  body.  Along  with  the  glyco- 
suria  there  is  hyperglycemia,  that  is,  an  increase  in  the  sugar- 
content  of  the  blood,  and  the  usual  explanation  for  this  action  of 
the  epinephrin  is  that  it  stimulates  the  process  of  glycogenolysis, 
the  process  by  which  the  stored  glycogen  of  the  liver  is  converted  to 
sugar  and  given  to  the  blood.  This  production  of  epinephrin 
glycosuria  has  been  observed  not  only  under  experimental  condi- 
tions, but  also  under  what  may  be  called  normal  conditions  in  which 
there  is  evidence  of  an  increased  secretion  or  hypersecretion  of  the 
gland.  Cannon  has  described,  for  example,  what  he  calls  emotional 
glycosuria,  a  condition  in  which  in  consequence  of  emotional 
excitement  there  is  an  increased  secretory  activity  of  the  adrenal 
gland  and  an  accompanying  glycosuria.  Results  of  this  kind  would 
seem  to  indicate  that  the  normal  secretion  of  epinephrin  may  play 
a  part  in  the  complex  sugar-regulating  mechanism  of  the  body, 
and  there  is  evidence,  which  will  be  referred  to  briefly  later,  that 
the  other  glands  of  internal  secretion,  or  some  of  them  at  any  rate, 
are  also  concerned  in  the  regulation  of  the  sugar  supply  and  sugar 
consumption.  When  administered  in  large  doses  epinephrin  has  a 


886  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

distinct  toxic  effect.  The  lethal  dose  varies  with  the  animal  used 
and  the  mode  of  administration.  When  given  intravenously  a 
dose  of  as  much  as  1  mgrm.  per  kilogram  of  body  weight  may  be 
followed  by  a  rapid  paralysis  of  respiration  or  of  the  heart,  or  by 
a  more  gradual  intoxication  accompanied  by  hemorrhages  from 
the  intestinal  mucosa. 

The  Secretory  Nerves  of  the  Adrenal  Gland. — The  adrenal  glands 
receive  a  supply  of  sympathetic  autonomic  nerve-fibers  by  way  of 
the  splanchnic  nerves.  Dreyer*  first  demonstrated  that  the  produc- 
tion of  epinephrin  in  the  gland  may  be  increased  upon  stimulation 
of  these  fibers  and  that  in  all  probability  the  output  of  epinephrin 
is  regulated  through  definite  secretory  fibers.  This  conclusion  has 
been  corroborated  by  more  recent  work.  Sensory  stimulations  of 
various  kinds,  strong  emotional  excitement,  and  other  conditions 
seem  to  cause  a  reflex  stimulation  of  the  gland  and  a  consequent  in- 
crease in  the  concentration  of  epinephrin  in  the  blood.  In  fact,  it 
would  appear  that  some  of  the  variations  in  arterial  pressure,  which 
have  been  explained  heretofore  as  the  immediate  result  of  direct  or 
reflex  stimulation  of  vasoconstrictor  fibers,  may  be  due  rather  to  a 
reflex  stimulation  of  the  adrenal  glands  which  brings  about  a  vaso- 
constriction  through  an  increased  amount  of  epinephrin.  When 
the  splanchnic  nerves  (peripheral  end)  are  stimulated,  for  example, 
a  marked  vasoconstriction  is  produced  throughout  the  so-called 
splanchnic  area.  Analysis  seems  to  show  than  in  this  case  there  is 
a  primary  constriction  due  to  the  action  of  the  vasomotor  fibers, 
but  this  is  followed  and  sustained  by  an  additional  constriction 
caused  by  the  increased  output  of  epinephrin. 

The  Functional  Significance  of  the  Medullary  Tissue. — The 
normal  functional  value  of  the  medullary  tissue  and  of  the  other 
chromaffin  tissues  consists,  so  far  as  we  know,  in  the  production  and 
secretion  of  epinephrin,  and  discussions  upon  this  question  have 
centered,  therefore,  upon  the  normal  occurrence  and  significance 
of  the  epinephrin.  Examination  of  the  venous  blood  flowing  from 
the  adrenal  gland  discloses  the  fact  that  it  contains  epinephrin. 
The  presence  of  the  base  is  shown  most  satisfactorily  by  its  physio- 
logical reactions.  When  the  blood  from  the  adrenal  vein  is  col- 
lected and  injected  into  another  animal  it  produces  the  character- 
istic epinephrin  effect  upon  blood-pressure;  other  similar  tests, 
such  as  the  dilatation  of  the  pupil  in  an  excised  eye  of  the  frog 
(Meltzer  reaction),  the  contraction  of  rings  of  arteries  (Meyer's 
test),  or  the  relaxation  of  strips  of  intestine  (Cannon-Hoskin),  all 
agree  in  indicating  that  the  venous  blood  flowing  from  the  adrenal 
gland  contains  epinephrin.  The  amount  is  small,  so  small  that 
attempts  to  demonstrate  its  existence  in  the  general  circulation 

*  Dreyer,  "American  Journal  of  Physiology,"  2,  283,  1899. 


SECRETION    OF    THE    DUCTLESS    GLANDS.  887 

have  not  been  entirely  satisfactory;  some  claim  to  have  shown  its 
presence,  while  others  get  negative  results.  It  is  generally  believed, 
however,  that  the  blood  does  receive  constantly  a  supply  of  epi- 
nephrin  from  the  adrenal  glands  and  that  this  constitutes  the  inter- 
nal secretion  of  the  medullary  cells.  As  regards  the  function  of  the 
epinephrin  under  normal  conditions  there  is  some  difference  of 
opinion.  The  usual  view  is  that  it  serves  to  maintain  a  condition 
of  tonicity  in  the  musculature  of  the  heart  and  blood-vessels  inner- 
vated by  the  sympathetic  autonomic  system  and  thus  insures  a 
normal  cardiovascular  tone.  If  the  amount  of  epinephrin  falls 
below  normal  or  fails  entirely,  a  condition  of  hypotension  results  in 
consequence  of  general  vascular  dilatation.  When  epinephrin  is 
secreted  in  excess  the  opposite  condition  of  hypertension  prevails. 
This  theory  is  not  accepted  by  some  of  the  workers  in  this  field.* 
They  state  that  experimental  injections  of  epinephrin  in  concen- 
trations equivalent  to  those  that  may  be  considered  normal  in  the 
blood,  cause  a  lowering  of  pressure  rather  than  an  increase,  possibly 
because  in  such  low  dosage  it  acts  upon  the  vasodilators  rather  than 
the  vasoconstrictors.  In  the  second  place  complete  removal  of  the 
adrenal  bodies  is  not  followed  by  a  prompt  loss  of  vascular  tone  as 
might  be  expected  on  the  theory  given  above.  An  alternative  or 
supplementary  theory  that  has  been  proposed  is  that  the  secretion 
of  epinephrin  constitutes  a  reserve  mechanism  that  comes  into  ac- 
tion at  times  of  stress.  Under  the  emotional  excitement  at  such 
times  there  is  a  reflex  excitation  of  the  sympathetic  autonomic  sys- 
tem, including  the  nerve  supply  to  the  adrenal  glands.  The  in- 
creased secretion  of  epinephrin  thus  produced  is  of  benefit  in  that 
it  facilitates  or  augments  the  response  of  the  sympathetic  nerves, 
giving  a  more  rapid  heart-beat,  a  greater  flow  of  blood  to  the  mus- 
cles, central  nervous  system,  and  heart,  and  also  by  increasing  the 
output  of  sugar  from  the  liver,  f  In  spite  of  the  large  amount  of 
experimental  work  upon  the  action  of  epinephrin,  it  seems  neces- 
sary at  present  to  recognize  the  fact  that  our  knowledge  is  too 
incomplete  to  justify  any  positive  statements  in  regard  to  its 
normal  role  in  the  organism. 

As  stated  above,  the  rise  of  blood-pressure  and  the  slow  heart- 
beat caused  by  injections  of  epinephrin  last  but  a  few  minutes. 
Apparently  the  excess  above  the  normal  concentration  in  the  blood 
is  quickly  destroyed  in  some  way.  Possibly  it  is  absorbed  and  oxi- 
dized or  otherwise  changed  by  the  tissues,  but  on  this  point  also 
experiments  as  yet  have  not  given  a  decisive  result.  { 

The  Functional  Significance  of  the  Cortical  Tissue. — Most  ob- 

*  Hoskins  and  McClure,  "Archives  of  Internal  Medicine,"  10,  343,  1912. 

t  See  Cannon,  "American  Journal  of  Psychology,"  25,  256,  1914. 

t  For  general  reviews  of  literature,  consult  Biedl,  "Innere  Sekretion,"  1913. 


888  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

servers  agree  that  the  cortex  does  not  contain  epinephrin.  This 
and  the  additional  fact  that  the  cortical  cells  have  a  different 
origin  embryologically  make  it  probable  that  its  functions  are 
different  from  those  of  the  medulla.  Biedl  has  shown  that  in 
those  fishes  in  which  the  cortical  substance  exists  as  a  sep- 
arate structure,  the  interrenal  body,  extirpation  of  this  organ 
is  followed  by  'a  condition  of  progressive  muscular  weakness 
ending  in  death.  This  result  would  indicate  that  the  corti- 
cal tissues  have  some  specific  and  essential  internal  secretion, 
and  it  would  seem  possible,  moreover,  that  the  fatal  result  al- 
ways following  extirpation  of  the  adrenal  bodies  is  due  to  loss  of 
the  cortical  rather  than  the  medullary  substance.  Some  experi- 
menters, who  have  studied  carefully  the  effects  of  partial  or  com- 
plete removal  of  the  adrenals  in  mammals,  record  their  opinion  that 
it  is  the  cortex  rather  than  the  medulla  that  is  essential  to  life.* 
The  nature  of  the  secretion  furnished  by  the  cortex  and  its  normal 
functional  value  are  matters  of  speculation  only  at  present. 
Chemical  examination  of  the  cortex  shows  the  presence  of  much 
lipoid  material,  particularly  of  the  cholesterin  esters,  and  it  may  be 
that  through  this  material  the  tissue  influences  the  metabolism  in 
other  parts  of  the  body. 

Observers  have  also  called  attention  repeatedly  to  the  fact  that 
the  cortex  has  some  relation  to  the  activity  of  the  sexual  glands. 
During  pregnancy  the  cortex  undergoes  hypertrophy,  and  in  some 
cases  pathological  changes  affecting  the  cortex  alone  have  been  fol- 
lowed by  precocious  development  of  the  sexual  organs.  On  the 
other  side,  castration  causes  changes  in  the  adrenal  bodies  and, 
indeed,  the  various  phases  of  sexual  life  are  accompanied  by  histo- 
logical  changes  in  the  adrenals.  But  others  of  the  glands  of  inter- 
nal secretion  have  some  similar  functional  relation  with  the  repro- 
ductive glands  or  their  contained  interstitial  tissue,  and  no  specific 
suggestion  can  be  offered  at  present  in  regard  to  the  particular  part 
taken  by  the  adrenal  cortex.f 

Pituitary  Body  (Hypophysis). — This  body  is  usually  described 
as  consisting  of  two  parts — a  large  anterior  lobe  of  distinct  glandu- 
lar structure  and  a  much  smaller  posterior  lobe  of  nervous  origin 
and  composed  chiefly  of  neuroglia  cells  and  fibers.  Embryologic- 
ally the  two  lobes  are  entirely  distinct.  The  anterior  lobe  arises 
from  an  invagination  (Rathke's  pouch)  of  the  buccal  ectoderm.  A 
portion  of  this  epithelium  soon  develops  into  a  glandular  structure, 
belonging  to  the  type  of  glands  which  have  no  excretory  duct  and 

*  Crowe  and  Wislocki,  "Johns  Hopkins  Hospital  Bulletin,"  October,  1914, 
and  Swale  Vincent,  "Endocrinology,"  1,  140,  1917. 

t  For  details  and  references  to  literature  on  this  and  other  points  in  inter- 
nal secretion  consult  the  excellent  work  by  Biedl,  "Innere  Sekretion,"  Berlin, 
1913,  and  "The  Endocrine  Organs,"  Schafer,  London,  1916. 


SECRETION    OF    THE    DUCTLESS    GLANDS. 


889 


which  probably,  therefore,  form  an  internal  secretion.  The  pos- 
terior lobe  arises  as  an  outgrowth  from  the  floor  of  the  third  ven- 
tricle of  the  brain,  the  infundibulum,  which  comes  into  contact 
with  the  epithelial  pouch  forming  the  anterior  lobe.  The  epithelial 
cells  of  the  latter  soon  show  a  differentiation  into  two  parts,  one  of 
which  gives  rise  to  the  anterior  lobe,  while  the  other  invests  the 
body  and  neck  of  the  posterior  or  nervous  lobe.  To  this  latter  the 
special  name  of  the  pars  intermedia  has  been  given.  When  fully 
formed  the  posterior  lobe  consists  of  two  parts,  the  pars  nervosa, 
composed  of  neuroglia  cells  and  fibers  and  ependymal  cells,  and  an 
investing  layer  of  epithelial  cells,  derived  from  the  buccal  ectoderm 
and  known  as  the  pars  intermedia  (see  Fig.  299). 


Fig.  299. — Median  sagittal  section  through  pituitary  of  monkey;  semidiagrammatic 
(Herring):  a,  Optic  chiasma;  b,  third  ventricle;  c,  g,  pars  intermedia;  d,  epithelium  of  pars 
intermedia  extending  round  neck  of  pars  nervosa;  e,  pars  glandularis  seu  epithelialis;  /,  intra- 
glandular  cleft,  lying  between  pars  glandularis  (e)  and  pars  intermedia  (g) ;  h,  pars  nervosa. 

In  the  pars  nervosa  characteristic  hyaline  or  colloid  bodies 
occur  and  histological  work  makes  it  probable  that  this  material 
constitutes  an  internal  secretion.  According  to  Herring,*  it  is 
formed  from  the  epithelium  of  the  pars  intermedia.  The  cells  of 
the  latter  invade  the  pars  nervosa,  undergo  a  hyaline  degeneration, 
and  are  finally  discharged  into  the  cerebrospinal  liquid  of  the  third 
ventricle.  Investigations  upon  the  physiology  of  the  pituitary 

*  Herring,  "Quarterly  Journal  of  Experimental  Physiology,"  1,  121,  161, 
281,  1908. 


890  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

gland  have  taken  the  two  usual  directions,  namely,  a  study  of  the 
effects  of  removal  and  a  study  of  the  effects  of  extracts,  and  obser- 
vations of  this  character  have  been  made  upon  this  gland  as  a 
whole  and  upon  the  anterior  and  posterior  lobes  taken  separately. 

Extracts  of  the  Posterior  Lobe. — Extracts  of  this  lobe  contain  ma- 
terial from  both  the  pars  nervosa  and  the  pars  intermedia,  but  on 
the  evidence  stated  above  it  may  be  assumed  that  the  results  ob- 
tained are  attributable  in  reality  to  the  pars  intermedia,  which  has 
a  glandular  structure  and  is  responsible  for  the  hyaline  material 
found  in  the  nervous  part.  When  extracts  of  the  posterior  lobe 
are  injected  into  the  circulation  several  distinct  results  have  been 
observed  to  follow.  In  the  first  place  there  is  a  characteristic  effect 
on  the  circulation — the  heart-rate  is  slowed  and  the  blood-pressure 
is  raised.  Both  effects  are  less  marked  than  in  the  case  of  epi- 
nephrin,  but  they  persist  for  a  longer  time.*  Further  examination 
has  shown  that  the  extracts  seem  to  exercise  a  stimulating  effect 
on  all  or  most  of  the  involuntary  muscles  in  the  body.  The  in- 
testine, bladder,  and  uterus  are  all  made  to  contract,  and  this  ef- 
fect is  perhaps  especially  marked  in  the  case  of  the  uterine  mus- 
cle, so  much  so  in  fact  that  it  has  been  proposed  to  use  such  ex- 
tracts in  obstetrical  practice  to  promote  the  contractions  of  the 
uterus.  While  the  epinephrin  acts  mainly  at  least  on  plain  muscle 
innervated  by  the  sympathetic  autonomies  and  gives  contraction  or 
relaxation  according  as  the  nerve-fibers  are  motor  or  inhibitory,  the 
hormone  from  the  posterior  lobe  of  the  pituitary  gland  appears  to 
act  directly  on  the  muscle  and  to  cause  contraction  or  increased 
tone  in  all  cases.  In  addition  to  this  effect  on  plain  muscle  the 
extracts  have  a  stimulating  action  on  several  kinds  of  glandular 
tissue,  f  They  cause  a  distinct  diuresis  by  an  effect  on  the  kidneys; 
they  act  as  a  galactogogue  to  the  mammary  glands  when  in  func- 
tional activity,  and  it  is  stated  that  they  accelerate  the  rate  of 
formation  of  cerebrospinal  liquid.  Lastly,  these  extracts  influence 
the  general  metabolism,  particularly  in  regard  to  the  carbohydrates. 
Like  the  epinephrin,  they  cause  a  glycosuria,  and  apparently  in  the 
same  way,  that  is,  by  accelerating  the  process  of  glycogenolysis  in 
the  liver. 

Extracts  of  the  Anterior  Lobe. — In  marked  contrast  to  the  effects 
obtained  from  the  posterior  lobe,  extracts  of  the  anterior  lobe  when 
injected  yield  no  immediate  results.  As  will  be  seen  below  this  lobe 
undoubtedly  furnishes  an  important  secretion,  but  the  specific 

*  Howell,  "Journal  of  Experimental  Medicine,"  3,  245,  1898;  also  Schafer 
and  Vincent,  "Journal  of  Physiology,"  25,  87,  1899. 

t  Schafer  and  Herring,  "Philosophical  Transactions  Royal  Society/' 
London,  B,  199,  1;  Ott  and  Scott,  "Proceedings  Society  of  Exp.  Biol.  and 
Med.,"  8,  28, 1910-11;  Weed  and  Gushing,  "American  Journal  of  Physiology," 
36,  77,  1915. 


SECRETION    OF    THE    DUCTLESS    GLANDS.  891 

action  of  this  secretion  is  not  revealed  by  the  method  of  injection. 
Robertson  has  isolated  a  substance  from  this  lobe  which  he  desig- 
nates as  tethelin.  It  contains  nitrogen  and  phosphorus  in  the 
ratio  of  4  to  1,  and  is  soluble  in  alcohol,  ether,  and  chloroform, 
although  it  may  be  precipitated  from  alcoholic  solution  by  the 
addition  of  ether.  The  author  states  that  administration  of  this 
material  to  mice,  like  the  use  of  extracts  of  the  entire  lobe,  has 
a  stimulating  effect  on  growth. 

Removal  of  the  Pituitary  >  Body. — Very  contradictory  reports 
were  made  by  the  earlier  observers  upon  the  result  of  the  complete 
removal  of  the  pituitary  body,  but  since  the  work  of  Paulesco  it 
has  been  generally  accepted  that  hypophysectomy  is  essentially  a 
fatal  operation.  *  The  animal  dies  in  a  few  days  after  exhibiting 
a  series  of  premonitory  symptoms,  such  as  a  fall  in  temperature, 
unsteady  gait,  rapid  emaciation,  and  diarrhea.  Further  examina- 
tion has  shown  that  this  fatal  outcome  happens  when  the  anterior 
lobe  alone  is  removed,  and  we  may  conclude,  therefore,  that  the 
secretion  of  this  gland  exercises  some  profoundly  important  influ- 
ence upon  metabolism,  although  the  nature  of  this  influence  is  not 
as  yet  understood.  Removal  of  the  posterior  lobe  alone  is  not 
fatal,  but  it  is  followed  by  characteristic  effects.  The  animal 
exhibits  a  greater  tolerance  to  carbohydrate  food,  that  is  to  say,  a 
larger  quantity  of  carbohydrate  can  be  taken  without  causing 
alimentary  glycosuria.  There  is  also  a  marked  increase  in  the 
processes  of  fat  formation,  so  that  a  tendency  to  obesity  is  one 
indication  of  a  diminished  activity  of  the  posterior  lobe.  When  the 
operation  is  performed  upon  young  animals  the  development  of  the 
sexual  glands  is  arrested,  and  the  animal  later  exhibits  a  eunuchoid 
condition.  On  the  clinical  side  observations  have  been  collected 
which  corroborate  and  extend  the  conclusions  that  might  be  drawn 
from  the  results  of  animal  experimentation,  although  in  such  cases 
it  has  been  more  difficult  to  separate  the  effects  due  to  the  anterior 
and  the  posterior  lobes  respectively.  When  the  hypophysis  is 
hypertrophied  and  is  presumably  in  a  condition  of  hyperactivity, 
the  resulting  effects  are  exhibited  chiefly  in  the  matter  of  the 
growth  of  the  skeleton.  In  early  life  such  an  effect  leads  to  marked 
overgrowth  or  gigantism,  while  in  later  life  it  occasions  an  enlarge- 
ment of  the  bones  of  the  face  and  extremities,  a  condition  known  as 
acromegaly.  It  is  assumed  that  in  such  cases  there  is  a  hyperseore- 
tion  of  the  anterior  lobe.  On  the  other  hand,  when  there  is  reason 
to  believe  that  there  is  a  diminished  activity  of  the  pituitary  body, 
for  example,  from  pathological  growths  pressing  upon  the  gland, 
the  effects  usually  observed  are  the  production  of  obesity  and  sexual 

*  See  Gushing,  "The  Pituitary  Body  and  Its  Disorders,"  1912;  also  Goetsch, 
"The  Quarterly  Journal  of  Medicine,"  January,  1914. 


892  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

infantilism,  together  with   increased  tolerance  to  carbohydrates. 
These  effects  are  attributed  to  a  hyposecretion  of  the  posterior  lobe. 

The  Functions  of  the  Pituitary  Body. — It  seems  evident  from  the 
above  brief  statement  of  the  results  of  experiments  and  clinical 
observations  that  the  pituitary  body  is  essential  in  some  way  to 
normal  body-metabolism,  and  moreover  that  the  anterior  and  pos- 
terior lobes  exercise  different  functions.*  The  differentiation  in 
function  between  the  two  parts  or  two  glands  cannot  be  made 
completely  at  present,  but  so  far  as  our  knowledge  goes  it  would 
seem  that  the  anterior  lobe  furnishes  a  secretion  that  stimulates 
the  growth  of  the  skeleton  and  possibly  the  connective  tissues  in 
general,  and  in  addition  exercises  some  deeper  influence  on  metabo- 
lism of  an  unknown  but  essential  nature.  The  posterior  lobe,  on 
the  contrary,  furnishes  one  or  several  hormones  that  have  a  stimu- 
lating effect  upon  several  processes — the  tone  of  plain  muscle,  the 
secretory  activity  of  several  glands,  and  the  process  of  glycogeno- 
lysis.  In  addition,  this  portion  of  the  gland  shares  with  others  of 
the  ductless  glands  (thymus,  cortex  of  the  adrenal  glands)  a  regu- 
lating influence  upon  the  normal  development  of  the  reproductive 
organs.  Its  influence  in  this  respect  resembles  and  may  be  con- 
nected with  the  activity  of  the  interstitial  tissue  within  the  sub- 
stance of  the  ovary  or  testis. 

The  Pineal  Body  (Epiphysis  Cerebri). — This  small  body 
projects  from  the  roof  of  the  third  ventricle  and  embryologically 
develops  as  an  outgrowth  from  this  vesicle  of  the  brain.  In  early 
life  it  has  a  glandular  structure  which  seems  to  reach  its  greatest 
development  at  about  the  seventh  year.  After  this  period  and 
particularly  after  puberty  it  undergoes  a  process  of  involution 
during  which  the  glandular  structure  gradually  disappears  and  its 
place  is  taken  by  fibrous  tissue.  The  gland  is  noteworthy  also  for 
the  appearance  of  calcareous  concretions,  the  so-called  brain  sand, 
which  may  appear  even  in  early  life.  Intravenous  injections  of  ex- 
tracts of  this  gland  seem  to  cause  a  distinct  fall  in  blood-pressure, 
indicating  the  presence  of  a  depressor  substance.  On  the  patho- 
logical side  it  is  stated  that  in  young  children  invasion  of  the  gland 
by  pathological  growths  results  in  distinctive  effects.  Under  such 
conditions  there  is  presumably  a  diminished  activity  of  the  gland, 
and  the  results  observed  are  an  accelerated  development  of  the 
reproductive  organs,  with  an  attending  mental  precocity  and  an 
increased  growth  of  the  skeleton.  The  inference  made,  therefore, 
from  these  observations  is  that  in  the  young  child  the  gland  fur- 
nishes a  secretion  which  inhibits  growth  and  particularly  restrains 
the  development  of  the  reproductive  glands,  but  it  should  be 
noted  that  this  conclusion  is  not  well  supported  by  experimental 
*  Consult  Schafer,  "The  Endocrine  Organs,"  London,  1916. 


SECRETION    OF    THE    DUCTLESS    GLANDS.  893 

evidence.  Total  extirpation  of  the  gland  gives  no  decisive  effect 
upon  dogs  (Dandy).  On  guinea-pigs  it  is  stated  (Horrax)  that 
pinealectomy  causes  an  accelerated  development  of  the  sexual 
organs  in  the  male. 

Organs  of  Reproduction. — Some  of  the  earliest  work  upon  the 
effect  of  the  internal  secretions  of  the  glands  was  done  upon  the 
reproductive  glands,  especially  the  testis,.  by  Brown-Sequard.* 
According  to  this  observer,  extracts  of  the  fresh  testis  when  in- 
jected under  the  skin  or  into,  the  blood  may  have  a  remarkable 
influence  upon  the  nervous  system.  Mental  and  physical  vigor, 
and  the  activity  of  the  spinal  centers,  are  greatly  improved,  not 
only  in  cases  of  general  prostration  and  neurasthenia,  but  also  in 
the  case  of  the  aged.  It  cannot  be  said  that  his  assertions  have 
been  corroborated  by  later  work.  Zothf  and  also  Pregel  seem  to 
have  obtained  exact  objective  proof,  by  means  of  ergographic 
records,  of  the  stimulating  action  of  the  testicular  extracts  upon  the 
neuromuscular  apparatus  in  man.  They  find  that  injections  of 
the  testicular  extracts  cause  not  only  a  diminution  in  the  muscular 
and  nervous  fatigue  resulting  from  muscular  work,  but  also  lessen 
the  subjective  fatigue  sensations.  The  natural  direction  in  which 
we  would  look  for  evidence  of  the  existence  of  an  internal  secretion 
on  the  part  of  the  testes  would  be  in  their  influence  upon  the  sexual 
characteristics  and  sexual  appetite.  Most  of  the  recent  work 
has  indicated  quite  clearly  that  the  reproductive  glands  control 
the  development  of  the  sexual  characteristics,  not  by  way  of  a 
reflex  nervous  effect  but  by  way  of  the  blood ;  that  is  to  say,  through 
an  internal  secretion.  This  work  however,  tends  to  show  that  the 
internal  secretion  is  formed  not  by  the  reproductive  elements 
proper,  the  spermatozoa  or  the  spermatogonia,  but  rather  by  the 
so-called  interstitial  cells  of  Leydig,  which  lie  outside  of  the  seminal 
tubules.  When  a  young  animal  is  castrated  completely  the  sec- 
ondary sexual  characters  and  the  sexual  appetite  do  not  develop. 
If,  however,  the  vas  deferens  is  ligated,  the  sexual  elements  may 
disappear  while  the  interstitial  cells  remain  and  increase  in  num- 
ber. In  such  animals  the  sexual  instincts  and  characteristics 
develop  normally.  The  clearest  proof  of  the  importance  of  the 
interstitial  cells  in  this  regard  is  furnished  by  the  experiments  of 
Steinach.J  Making  use  of  very  young  animals  this  observer  has 
transplanted  the  testes  from  their  normal  position  to  other  regions. 
Such  annuals  develop  normally,  show  all  of  the  usual  secondary 
sexual  characteristics,  and  manifest  full  sexual  desire  and  potency 
at  the  proper  period.  When  the  transplanted  glands  are  examined 

*  "Archives  de  physiologic  normals  et  pathologique,"  1889-92. 
t"Pfliiger's  Archiv  f.  die  gesammte  Physiologic,"  62,  335,  1896;  also  69, 
386,  1897. 

t  Steinach,  "Pflugef's  Archiv,"  144,  71,  1912. 


894  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

it  is  found  that  the  sexual  elements  are  lacking,  but  the  interstitial 
cells  are  increased  in  amount.  It  would  appear  from  this  work 
that  sexual  puberty  is  dependent  upon  the  internal  secretion 
furnished  by  these  cells,  and  Steinach  proposes  to  designate  them 
collectively  as  the  "puberty  gland."  This  observer  reports  further 
remarkable  experiments  in  which  young  males  (rats,  guinea  pigs) 
were  first  castrated  and  then  had  transplanted  under  the  skin  or 
in  the  peritoneal  cavity  the  ovary  from  a  female  of  the. same 
species.  Under  such  conditions  the  graft  of  the  ovary  takes,  and 
unlike  the  grafted  testicle  both  the  reproductive  cells  and  the 
interstitial  cells  survive.  In  such  animals  the  secondary  male 
characteristics  do  not  develop,  his  genital  organs  remain  infantile; 
he  exhibits,  on  the  contrary,  the  female  characteristics,  as  shown  by 
his  size,  the  character  of  the  hair,  and  especially  by  the  develop- 
ment of  mammae  and  nipples.  So  far  as  the  external  charac- 
teristics are  concerned  the  animal  is  completely  feminized,  and 
Steinach  states  that  such  an  animal  is  sought  by  the  male  as 
though  it  were  a  true  female.  It  would  follow  from  these  experi- 
ments that  the  internal  secretion  of  the  interstitial  cells  in  the  ovary 
and  in  the  testis  has  each  its  specific  influence  in  guiding  the  de- 
velopment of  the  sexual  characteristics,  one  causing  the  formation 
of  male,  the  other  of  female  characteristics.  Many  experiments 
and  observations  indicate  that  the  internal  secretions  of  the  ovaries 
and  testes  are  important,  not  only  as  regards  so-called  secondary 
sexual  characteristics,  but  also  in  regard  to  the  body-metabolisms  in 
general.  Some  evidence  for  this  general  view  is  found  in  the 
functional  relationship  that  appears  to  exist  between  these  organs 
and  other  ductless  glands.  This  relationship  is  most  clearly 
marked  with  the  thymus,  the  pituitary,  and  the  cortical  portion  of 
the  adrenal  glands.  Castration  or  spaying  causes  an  enlargement 
of  the  thymus  gland,  even  in  the  mature  animal  in  which  this  gland 
has  undergone  considerable  involution.  The  same  operation 
affects  the  hypophysis  and  adrenals,  although,  according  to  Hatai,* 
the  effect  in  this  case  varies  with  the  sex.  In  the  male  castration 
causes  a  marked  increase  in  the  weight  of  the  hypophysis,  while  in 
the  female  the  effect  is  less  distinct.  As  regards  the  adrenal  glands, 
castration  in  the  male  causes  an  increased  weight  of  the  adrenals, 
while  spaying  in  the  female  causes  a  decrease  in  weight  in  these 
glands.  On  the  other  hand,  as  has  been  stated  above,  thymectomy 
seems  to  accelerate  the  development  of  the  reproductive  glands, 
and  removal  of  the  posterior  lobe  of  the  hypophysis  retards  their 
development.  The  nature  of  these  reciprocal  relationships  can- 
not be  explained  at  present,  but  it  may  be  assumed  that  they  are 
concerned  with  modifications  of  the  nature  of  some  of  the  processes 

*  Hatai,  "The  Journal  of  Experimental  Zoology,"  18,  1,  1915. 


SECRETION    OF    THE    DUCTLESS    GLANDS.  895 

of  body-metabolism  and  that  the  effects  produced  depend  upon 
definite  hormones  or  internal  secretions.  Further  evidence  of  the 
same  character  may  be  found  in  observations  like  the  following: 
In  gynecological  practice  it  has  been  observed  that  complete 
ovariotomy  with  its  resulting  premature  menopause  is  often 
followed  by  distressing  symptoms,  mental  and  physical.  In 
such  cases  many  observers  have  reported  that  these  symptoms 
may  be  alleviated  by  the  use  of  ovarian  extracts.  Similar  results 
have  been  reported  upon  the  lower  animals.  After  complete  ovari- 
otomy a  condition  of  "heat"  may  be  reproduced  by  grafting  ovarian 
tissue,  *  and  several  observers  agree  in  stating  that  removal  of  the 
ovaries  in  young  animals  prevents  the  normal  development  of  the 
uterus,  while  in  adult  animals  it  causes  the  organ  to  undergo  a 
fibrous  degeneration  (see  section  on  Reproduction).  In  the 
natural  menopause,  as  well  as  in  the  premature  menopause  follow- 
ing complete  removal  of  the  ovaries,  it  is  a  frequent,  though  not 
invariable,  result  for  the  individual  to  gain  noticeably  in  weight. 
An  effect  of  the  ovaries  on  general  nutrition  is  indicated  also  by 
the  interesting  fact  that  in  cases  of  osteomalacia,  a  disease  charac- 
terized by  softening  of  the  bones,  removal  of  the  ovaries  may 
exert  a  favorable  influence  upon  the  course  of  the  disease.  These 
indications  have  found  some  experimental  verification  in  a  research 
by  Loewy  and  Richterf  made  upon  dogs.  These  observers 
report  that  complete  removal  of  the  ovaries,  although  at  first 
apparently  without  effect,  resulted  in  the  course  of  two  to  three 
months  in  a  marked  diminution  in  the  consumption  of  oxygen  by 
the  animal,  measured  per  kilogram  of  body  weight.  If  now  the 
animal  in  this  condition  was  given  ovarian  extracts  (oophorin  tab- 
lets), the  amount  of  oxygen  consumed  was  not  only  brought  to 
its  former  amount,  but  considerably  increased.  A  similar  result 
was  obtained  when  the  extracts  were  used  upon  castrated  males. 
Schafer  states  that  extracts  of  the  ovaries  contain  two  substances, 
one  of  which  (interstitial  cells)  inhibits  contractility  of  plain  muscle, 
especially  the  muscle  of  the  uterus,  while  the  other  augments  this 
contractility .  J  While  the  effects  described  above  may  be  re- 
ferred mainly  to  the  internal  secretion  of  the  interstitial  cells  of 
the  ovaries,  other  facts  indicate  that  other  elements  in  the  gland 
may  also  furnish  a  specific  secretion.  Thus,  the  implantation 
of  the  fertilized  ovum  in  the  uterine  mucous  membrane  and  the 
development  of  the  placenta  have  been  supposed  to  be  effected 
through  the  agency  of  some  chemical  stimulus  arising  in  the  cells 
of  the  corpus  luteum  (see  section  on  Reproduction). 

*  Marshall  and  Jolly,  "Physiological  Transactions,"  B.  cxxvii.,  99,  1905. 
t  Loewy  and  Richter,  "Archiv  f.  Physiologic,"  1889,  suppl.  volume,  p.  174. 
j  Schafer,  "The  Endocrine  Organs,"  p.  141,  1917. 


PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

Pancreas. — The  importance  of  the  external  secretion,  the  pan- 
creatic juice,  of  the  pancreas  has  long  been  recognized,  but  it  was 
not  until  1889  that  von  Mering  and  Minkowski*  proved  that  it  fur- 
nishes also  an  equally  important  internal  secretion.     These  observers 
succeeded  in  extirpating  the  entire  pancreas  without  causing  the 
immediate  death  of  the  animal,  and  found  that  in  all  cases  this 
operation  was  followed  by  the  appearance  of  sugar  in  the  urine  in 
considerable  quantities.     Further  observations  of  their  own  and  of 
other  experimenters  have  corroborated  this  result  and  added  a  num- 
ber of  interesting  facts  to  our  knowledge  of  this  side  of  the  activity 
of  the  pancreas.    It  has  been  shown  that  when  the  pancreas  is  com- 
pletely removed  a  condition  of  glycosuria  inevitably  follows,  even 
if  carbohydrate  food  is  excluded  from  the  diet.    Moreover,  as  in 
the  similar  pathological  condition  of  glycosuria  or  diabetes  mel- 
litus  in  man,  there  is  an  increase  in  the  quantity  of  urine  (polyuria) 
and  of  urea,  and  an  abnormal  thirst  and  hunger.    Acetone  also  is 
present  in  the  urine,  but  not  to  the  same  extent  as  is  found  in 
human  diabetes.     These  symptoms  in  cases  of  complete  extir- 
pation of  the  pancreas  are  followed  by  emaciation  and  muscular 
weakness,  which  finally  end  in  death  in  two  to  four  weeks.     If  the 
pancreas  is  incompletely  removed,  the  glycosuria  may  be  serious, 
or  slight  and  transient,  or  absent  altogether,  depending  upon  the 
amount  of  pancreatic  tissue  left.  .  According  to  the  experiments 
of  von  Mering  and  Minkowski  on  dogs,  a  residue  of  one-fourth  to 
one-fifth  of  the  gland  is  sufficient  to  prevent  the  appearance  of  sugar 
in  the  urine,  although  a  smaller  fragment  may  suffice  apparently 
if  its  physiological  condition  is  favorable.    The  portion  of  pancreas 
left  in  the  body  may  suffice  to  prevent  glycosuria,  partly  or  com- 
pletely, even  though  its  connection  with  the  duodenum  is  entirely 
interrupted,  thus  indicating  that  the  suppr<^ion  of  the  pancreatic 
juice  is  not  responsible  for  the  glycosuria.    The  same  fact  is  shown 
more  conclusively  by  the  following  experiments:   Glycosuria  after 
complete  removal  of  the  pancreas  from  its  normal  connections  may 
be  prevented  partially  or  completely  by  grafting  a  portion  of  the 
pancreas  elsewhere  in  the  abdominal  cavity  or  even  under  the  skin. 
So  also  the  ducts  of  the  gland  may  be  completely  occluded  by  liga- 
ture or  by  injection  of  paraffin  without  causing  a  condition  of  per- 
manent glycosuria. 

On  the  basis  of  these  and  similar  results  it  is  believed  that  the 
pancreas  forms  an  internal  secretion  which  passes  into  the  blood 
and  plays  an  important,  indeed,  an  essential  part  in  the  metabolism 
of  sugar  in  the  body.  Moreover,  considerable  evidence  has  been 
accumulated  to  show  that  the  tissue  concerned  in  this  important 

*  Minkowski,  "Archiv  f.  exper.  Pathologic  u.  Pharmakologie,"  31,  85, 
1893. 


SECRETION    OF    THE    DUCTLESS    GLANDS.  897 

function  is  not  the  pancreatic  tissue  proper,  but  that  composing  the 
so-called  islands  of  Langerhans.  In  man  these  islands  are  scattered 
through  the  pancreas,  forming  spherical  or  oval  bodies  that  ma}' 
reach  a  diameter  of  as  much  as  one  millimeter.  The  cells  in  these 
bodies  are  polygonal;  their  cytoplasm  is  pale,  finely  granular,  and 
small  in  amount.  The  nuclei  possess  a  thick  chromatin  network 
which  stains  deeply.  Each  island  possesses  a  rich  capillary  network 
that  resembles  somewhat  the  glomerulus  of  the  kidney. 

According  to  Ssbolew,*  ligation  of  the  pancreatic  duct  is  followed 
by  a  complete  atrophy  of  the  pancreatic  cells  proper,  while  those 
of  the  islands  of  Langerhans  are  not  affected.  Since  under  these 
conditions  no  glycosuria  occurs,  while  removal  of  the  whole  organ 
including  the  islands  is  followed  by  pancreatic  diabetes,  the  obvious 
conclusion  is  that  the  diabetes  is  due  to  the  loss  of  the  islands. 
This  conclusion  is  strengthened  by  reports  from  the  pathological 
side.  A  number  of  observers  (Opie,  Ssbolew,  Herzog,  et  al.) 
find  that  in  diabetes  mellitus  in  man  the  islands  may  be  markedly 
affected.  They  show  signs  of  hyaline  degeneration  or  atrophy,  or 
in  severe  cases  may  be  absent  altogether.  It  should  be  added  that 
this  connection  of  the  islands  of  Langerhans  with  the  internal 
secretion  of  the  pancreas  is  not  accepted  by  all  writers.  Cases 
of  diabetes  are  reported  in  which  the  islands  were  apparently  not 
affected,  f  and  several  observers  }  contend  that  the  islands  represent 
stages  in  the  development  of  the  ordinary  secreting  alveoli  of  the 
pancreas.  The  most  complete  histological  work  seems  to  show 
clearly  that  the  islets  are  permanent  organs  which  persist  as  such  in 
the  pancreas,  and  presumably  have,  therefore,  some  specific  func- 
tional importance,  but  the  nature  of  this  function  and  its  relation 
to  that  of  the  acinar  cells  must  be  considered  at  present  as  open 
questions.  § 

Several  theories  have  been  advanced  to  explain  the  action  of 
the  internal  secretion  of  the  pancreas.  It  has  been  suggested  that 
the  secretion  contains  an  enzyme  which  is  necessary  in  the  hydrol- 
ysis or  oxidation  of  the  sugar  of  the  body,  and  in  the  absence  of 
this  enzyme  the  sugar  accumulates  in  the  blood  and  is  drained  off 
through  the  kidney.  In  support  of  this  explanation  it  is  found 
that  the  respiratory  quotient  of  the  depancreatized  dog  is  low,  as 
would  be  expected  if  the  sugar  escaped  oxidation.  Apparently 
something  is  lacking  in  the  normal  process,  but  as  the  nature 

*  "Virchow's  Archiv,"  168,  91,  1902;  also  Romans,  "The  Journal  of  Med- 
ical Research,"  30,  49,  1914. 

t  See  Pratt,  "Journal  of  the  American  Medical  Association,"  December  17, 
1910. 

t  Dale,  "Philosophical  Transactions,"  B,  cxcvii.,  1904;  also  Vincent  and 
Thompson,  "Journal  of  Physiology,"  1906,  xxvii.,  xxxiv. 

§  Bensley,  "American  Journal  of  Anatomy,"  12,  297,  1912. 

57 


898  PHYSIOLOGY    OF    DIGESTION    AND    SECRETION. 

of  the  normal  process  is  itself  incompletely  known,  the  defect 
caused  by  the  failure  of  the  pancreatic  hormone  becomes  cor- 
respondingly difficult  to  define.  Clark*  reports  some  recent  ex- 
periments in  which  he  perfused  the  heart  and  pancreas,  singly  and 
together,  with  a  Ringer  solution  containing  dextrose,  the  per- 
fusion  being  carried  out  under  aseptic  conditions.  When  the 
pancreas  alone  was  perfused  the  dextrose  suffered  a  change  in 
optical  rotation  without  any  alteration  in  reducing  power. 
When  the  heart  and  pancreas  were  perfused  together  or  in  sequence 
the  dextrose  suffered  a  diminution  in  both  optical  rotation  and  re- 
ducing power.  Since  both  of  these  properties  were  restored  in 
part  toward  normal  on  subsequent  hydrolysis  of  the  perfused 
liquid  it  would  seem  that  the  dextrose  had  undergone  a  con- 
densation to  some  form  of  polysaccharid.  The  author  suggests 
that  the  pancreas  furnishes  some  substance,  presumably  an  enzyme, 
which  causes  a  preliminary  change  in  the  dextrose  of  an  unknown 
nature,  but  probably  a  condensation.  When  this  material  is 
brought  to  the  heart  or  other  tissues  there  is  a  further  change  to  a 
form  of  carbohydrate  which  is  especially  adapted  for  utilization. 
This  action  of  the  pancreas  seems  to  be  limited  to  dextrose; 
levulose,  at  least,  is  not  affected  in  a  similar  way.  Other  investi- 
gators adopt  an  entirely  different  view  of  the  relation  of  the  pancreas 
to  carbohydrate  metabolism.  They  believe  that  the  internal  secre- 
tion of  the  pancreas  regulates  in  some  way  the  output  of  sugar 
from  the  liver.  In  the  absence  of  this  secretion  the  liver  gives  off  its 
glycogen  as  sugar  too  rapidly,  the  sugar  contents  of  the  blood  are 
thereby  increased  (hyperglycemia)  above  normal,  and  the  excess 
passes  out  in  the  urine.  The  large  amount  of  work  that  has  been 
done  upon  pancreatic  diabetes,  as  well  as  diabetes  mellitus  in  man, 
seems  to  favor  the  general  view  that  in  these  conditions  the  dif- 
ficulty lies  not  in  the  processes  of  glycogenesis  or  glycogenolysis, 
but  in  the  consumption  of  sugar  by  the  tissues.  In  pancreatic 
diabetes  certainly  the  balance  of  evidence  supports  the  theory  of 
an  internal  secretion  on  the  part  of  the  pancreas,  which  plays  an 
essential  r61e  in  the  normal  process  of  sugar  consumption  in  the 
tissues.  One  very  striking  bit  of  evidence  in  this  direction  is 
furnished  by  Carlson  f  and  his  co-workers.  They  find  that  if 
extirpation  of  the  pancreas  is  effected  in  a  pregnant  dog  near  term, 
the  animal  does  not  exhibit  glycosuria  until  the  pups  are  born  or 
are  removed  by  cesarean  section.  The  internal  secretion  from  the 
fetal  pancreas  suffices  to  protect  the  mother. 

*  Clark,  "Journal  of  Exp.  Medicine,"  1917. 

t  Carlson  and  Drennan,  "American  Journal  of  Physiology,"  28,  391,  1911; 
also  36,  217,  280,  1915,  and  "Journal  of  Biological  Chemistry,"  13,  465,  and 
17,  19. 


SECTION  VIII. 

NUTRITION  AND  HEAT  PRODUCTION  AND 
REGULATION. 


CHAPTER  XLVII. 
GENERAL  METHODS-HISTORY  OF  THE  PROTEIN  FOOD. 

Under  the  head  of  nutrition  or  general  metabolism  we  include 
usually  all  those  changes  that  occur  in  our  foodstuffs  from  the  time 
that  they  are  absorbed  from  the  alimentary  canal  until  they  are 
eliminated  in  the  excretions.  In  many  of  these  processes  the  oxygen 
absorbed  from  the  lungs  takes  a  most  important  part,  and  the 
changes  directly  due  to  this  element,  the  physiological  oxidations 
of  the  body,  can  not  be  separated  from  the  general  metabolic  phe- 
nomena of  the  tissues.  As  was  said  in  another  place,  the  respiratory 
history  of  oxygen  ceases  after  this  element  has  reached  the  tissues; 
its  subsequent  participation  in  the  chemical  changes  of  the  organ- 
ism forms  an  integral  part  of  the  nutritional  processes.  These  latter 
processes  are  varied  and  complex  and  only  partially  understood. 
For  the  sake  of  simplicity  in  presentation  it  is  convenient  to  con- 
sider separately  each  of  the  so-called  foodstuffs, — the  proteins, 
carbohydrates,  fats,  water,  and  inorganic  salts, — and  attempt  to 
trace  its  nutritive  history  from  the  time  it  is  absorbed  into  the 
blood  until  it  is  eliminated  from  the  body  in  the  form  of  excretory 
products.  Before  undertaking  this  description  it  is  desirable  to 
call  attention  to  certain  general  methods  and  conceptions  that 
have  been  developed  in  connection  with  this  part  of  physiology. 

Nitrogen  Equilibrium. — Among  our  main  foodstuffs  the  pro- 
teins are  characterized  by  containing  nitrogen.  After  this  ma- 
terial is  metabolized  in  the  body  the  nitrogen  is  eliminated  in 
various  forms,  chiefly  in  the  urine,  but  to  a  smaller  extent  in 
the  feces  and  sweat.  In  the  feces,  moreover,  there  may  be  pres- 
ent some  undigested  protein  which,  although  taken  with  the 
food,  has  never  really  entered  the  body.  It  is  evident  that  the 
urine,  feces  (and  sweat)  may  be  collected  during  a  given  period  and 
analyzed  to  determine  their  contents  in  nitrogen.  The  sweat  is 

899 


900  NUTRITION    AND    HEAT    REGULATION. 

usually  neglected  except  in  observations  upon  conditions  in  which 
muscular  activity  has  been  a  prominent  feature.  As  a  rule,  the 
amount  of  nitrogen  is  determined  by  some  modification  of  the  Kjel- 
dahl  method.  In  principle  this  method  consists  in  heating  the 
material  to  be  analyzed  with  strong  sulphuric  acid.  The  nitrogen 
is  thereby  converted  to  ammonia,  which  is  distilled  off  and  caught 
in  a  standardized  solution  of  sulphuric  acid.  By  titration  the 
amount  of  ammonia  can  be  determined,  and  from  this  the  amount  of 
nitrogen  is  estimated.  Nitrogen  forms  a  definite  percentage  of  the 
protein  molecule  (about  16  per  cent.) ;  so  that  if  the  weight  of  nitro- 
gen is  multiplied  by  6.25  the  weight  of  protein  from  which  it  is  de- 
rived is  obtained.  If,  on  the  other  hand,  the  nitrogen  is  determined 
in  the  food  eaten  during  the  period  of  the  experiment  it  is  evident 
that  a  balance  may  be  struck  which  will  determine  whether  the 
body  is  receiving  or  losing  nitrogen.  If  the  balance  is  even  the  body 
is  in  nitrogen  equilibrium — that  is,  it  is  receiving  in  the  food  as 
much  protein  nitrogen  as  it  is  metabolizing  and  eliminating  in 
the  excreta.  If  there  is  a  plus  balance  in  favor  of  the  food  it  is 
evident  that  the  body  is  laying  on  or  storing  protein,  while  if 
the  balance  is  minus,  the  body  must  be  losing  protein.  During 
the  period  of  growth,  in  convalescence,  etc.,  the  body  does  store 
protein,  and  under  these  conditions  the  balance  is  in  favor  of  the 
food  nitrogen.  But  throughout  adult  life  under  normal  conditions 
our  diet  is  so  regulated  by  the  appetite  that  a  nitrogen  equilibrium 
is  maintained  through  long  periods.  Under  experimental  condi- 
tions, involving,  for  instance,  a  special  diet,  it  often  becomes  neces- 
sary to  make  the  analyses  for  nitrogen  in  order  to  determine  whether 
or  not  the  individual  is  losing  or  gaining  protein  or  is  in  equilibrium. 
It  is  important  also  to  bear  in  mind  that  nitrogen  or  protein 
equilibrium  may  be  established  at  different  levels.  If,  for  instance, 
a  man  is  in  nitrogen  equilibrium  on  a  diet  containing  10  gms.  of 
nitrogen  per  day,  what  will  happen  if  the  protein  in  this  diet  is 
doubled?  Our  experience  teaches  us  that  the  extra  10  gms.  of  nitro- 
gen or  62.5  gms.  of  protein  are  not  stored  in  the  body  indefinitely. 
As  a  matter  of  fact,  the  extra  protein  is  metabolized  in  the  body  and 
nitrogen  equilibrium  becomes  established  at  a  higher  level.  Where- 
as under  the  first  condition  10  gms.  of  nitrogen  entered  the  body 
in  the  form  of  protein  and  10  gms.  of  nitrogen  left  the  body  in  the 
form  of  nitrogenous  excreta,  under  the  second  condition  20  gms. 
of  nitrogen  are  consumed  per  day  in  the  food  and  20  gms.  are 
lost  per  day  in  the  excretions.  The  total  mass  of  protein  tissue  in 
the  body  may  remain  the  same,  or  if  any  increase  takes  place  at  the 
beginning  of  the  change  in  diet  it  soon  ceases.  Experimentally  it  is 
found  that  there  is  a  certain  low  limit  of  protein  which  just  suffices 
to  maintain  nitrogen  equilibrium,  and  between  this  level  and  the 


GENERAL    METHODS — HISTORY    OF    PROTEIN    FOOD.  901 

capacity  of  the  body  to  digest  and  absorb  protein  food,  nitrogen 
equilibrium  may  be  maintained  upon  any  given  amount  of  protein. 

Carbon  Equilibrium  and  Body  Equilibrium. — The  term  "car- 
bon equilibrium"  is  sometimes  used  to  describe  the  condition  in 
which  the  total  carbon  of  the  excreta  (in  the  carbon  dioxid,  urea, 
etc.)  is  balanced  by  the  carbon  of  the  food.  It  is  possible  that  an 
individual  may  be  in  nitrogen  equilibrium  and  yet  be  losing  or  gain- 
ing in  weight,  since,  although  the  consumption  of  proteins  may  just 
be  covered  by  the  proteins  of  the  food,  so  far  as  the  nitrogen  is  con- 
cerned, the  supply  of  food  may  be  greater  than  the  body  needs  or 
can  destroy,  and  the  excess  may  be  stored  in  the  body  in  the  form  of 
glycogen  or  fat,  or,  on  the  other  hand,  the  supply  of  energy-yielding 
food  may  be  less  than  is  necessary  to  cover  the  needs  of  the  body 
and  some  of  the  fat  of  the  body  may  be  oxidized.  In  the  first  case 
the  carbon  absorption  would  exceed  the  carbon  excretion — there 
would  be  a  plus  carbon  balance;  in  the  second  case  the  reverse 
would  hold.  In  the  same  way  we  may  speak  of  a  water  equilibrium 
or  a  salts  equilibrium,  although  these  terms  are  not  generally  used. 
An  adult  under  normal  conditions  lives  so  as  to  maintain  a  gen- 
eral body  equilibrium;  his  ingestaof  all  kinds  are  balanced  by  the 
corresponding  excretions,  and  the  individual  maintains  a  practi- 
cally constant  body-weight. 

Complete  Balance  Experiments — Respiration  Chamber. — 
According  to  the  statements  made  in  the  last  paragraph,  it  is  obvious 
that  if  the  analytical  work  is  properly  done,  an  exact  balance  may 
be  drawn  between  the  proteins/  fats,  and  carbohydrates  eaten  as 
food  and  the  proteins,  fats,  and  carbohydrates  destroyed  in  the 
body  as  represented  by  the  nitrogen  and  carbon  contained  in  the 
excreta.  Complete  experiments  of  this  kind  were  attempted  first 
by  Voit  *  and  Pettenkofer,  to  whose  work  much  of  our  fundamental 
knowledge  is  due.  In  the  experiments  of  these  authors,  made  upon 
men  as  well  as  animals,  the  total  nitrogen  of  the  urine  and  feces  was 
determined  and  the  total  quantity  of  C02  given  off  from  the  lungs 
was  estimated.  This  last  determination  was  made  possible  by 
placing  the  individual  in  a  specially  constructed  chamber  or  respi- 
ration apparatus.  Air  was  drawn  through  this  room  by  means  of 
a  pump.  The  total  quantity  of  air  passing  through  the  room  was 
measured  by  a  gasometer  and  definite  fractions  were  drawn  off 
from  time  to  time,  which  were  analyzed  for  CO2.  From  the 
figures  thus  obtained  it  was  possible  to  estimate  the  entire  CO2 
given  off  during  the  period  of  observation.  Knowing  the  total 
nitrogen  and  carbon  eliminated,  it  was  possible  to  estimate  the 
amount  of  protein  and  fat  or  carbohydrate  destroyed  in  the  body. 
From  the  nitrogen  the  quantity  of  protein  metabolized  was 
*  See  Hermann's  "  Handbuch  der  Physiologic,"  vol.  vi.,  1881. 


902  NUTRITION    AND    HEAT    REGULATION. 

obtained  by  multiplying  by  6.25,  as  explained  above.  If  then 
the  carbon  belonging  to  the  amount  of  protein  metabolized  was 
deducted  from  the  total  carbon  excreta,  what  was  left  represented 
either  fat  or  carbohydrate  burnt  in  the  body,  and,  knowing  the 
amount  of  these  materials  taken  in  the  diet,  it  was  possible  to 
ascertain  whether  the  corresponding  amount  of  carbon  had  all 
been  excreted.  By  experiments  of  this  kind  a  nearly  perfect 
balance  may  be  struck  between  the  income  and  the  outgo  of  the 
body.  Absolute  accuracy  is  not  sought  for,  since  the  materials 
eaten  vary  somewhat  in  composition  and  some  little  of  the  carbon 
or  nitrogen  excreted  is  found  in  the  secretions  from  the  skin,  the 
saliva,  etc.,  which  are  not  usually  examined. 

More  recent  experiments  made  in  this  country  under  the  direc- 
tion of  Atwater*  have  attempted  to  balance  not  only  the  material 
income  and  outgo  of  the  body  during  a  given  period,  but  also  the 
income  and  outgo  of  energy.  For  this  purpose  the  individuals  ex- 
perimented upon  were  placed  in  a  very  carefully  constructed  respi- 
ration chamber  so  that  their  expired  air  could  be  analyzed  as  well 
as  the  urine  and  feces.  .The  chamber,  however,  was  also  arranged 
to  act  as  a  calorimeter  (see  p.  963)  by  means  of  which  the  heat  given 
off  by  the  person  could  be  measured.  The  heat  value  of  the  diet 
being  known,  it  is  possible  in  this  way  to  ascertain  whether  or  not 
this  theoretical  amount  of  heat  is  actually  given  off  from  the  body. 
Atwater's  respiration  chamber  is  described  as  a  respiration  calorim- 
eter; some  of  the  results  obtained  from  its  use  are  referred  to 
later  on. 

The  Effect  of  Non-protein  Food  on  Nitrogen  Equilibrium. — 
By  use  of  the  methods  referred  to  above  the  general  influence  of 
the  non-protein  foods  (fats,  carbohydrates)  upon  the  protein 
consumption  of  the  body  has  been  made  evident.  An  animal 
may  be  brought  into  nitrogen  equilibrium  on  protein  food  alone, 
the  amount  of  protein  required  being  relatively  large.  If  now 
non-protein  foodstuffs  are  added  to  the  diet  it  is  found  that  the 
amount  of  protein  necessary  to  maintain  nitrogen  equilibrium  may 
be  reduced  correspondingly.  With  reference  to  the  consumption 
of  protein  in  the  body  the  non-protein  foods  are  all  protein-spar ers, 
and  herein  lies  one  great  peculiarity  of  their  nutritional  value. 
On  a  mixed  diet  of  protein  and  non-protein  food  the  proportion  of 
the  latter  may  be  increased  and  that  of  the  former  decreased  to  a 
marked  extent  without  breaking  down  nitrogen  equilibrium — • 
that  is,  without  causing  a  loss  of  protein  tissue  from  the  body. 
This  fact  is  explained  by  the  consideration  that  in  our  body  the 
food  fulfils  two  great  functions.  First,  it  furnishes  the  material 
for  the  formation  of  new  living  matter  or  the  replacement  of 
*  Atwater,  Bulletins  45,  63,  69,  United  States  Department  of  Agriculture. 


GENERAL    METHODS — HISTORY    OF    PROTEIN    FOOD.  903 

the  loss  of  this  matter  that  is  continually  going  on;  second, 
it  furnishes  a  supply  of  energy  for  the  heat  of  the  body  and  for  the 
work  done  by  the  various  cells,  the  contraction  of  the  muscle,  the 
secretion  of  the  gland,  the  discharges  of  the  nerve-cells,  etc.  This 
second  function,  the  energy  requirement,  is  met  by  any  of  the  three 
energy-yielding  food-stuffs,  carbohydrates,  fats,  or  proteins,  es- 
pecially, as  we  shall  find,  by  the  carbohydrates.  For  the  first 
function  protein  (or  its  split-products)  is  absolutely  needed,  and 
perhaps  is  alone  needed.  In  any  event,  if  the  supply  of  non-pro- 
tein is  sufficiently  large,  then  the  amount  of  protein  can  be  lowered 
to  a  certain  irreducible  minimum,  which  is  required  for  purposes 
of  genuine  assimilation,  that  is,  the  construction  of  living  material. 

The  Nutritive  History  of  the  Protein  Food. — The  digestive 
changes  undergone  by  protein  and  its  subsequent  absorption  have 
been  described  in  the  section  on  Digestion.  It  will  be  remembered 
that  the  view  adopted  was  that  the  proteins  are  completely  hydro- 
lyzed  into  their  amino-acids  and  in  this  form  are  absorbed  into  the 
blood  and  distributed  to  the  tissues.  The  blood  from  the  intes- 
tines passes  first  through  the  liver  before  reaching  the  general  cir- 
culation, and  a  question  to  be  determined  is  whether  the  amino- 
acids  are  acted  upon  in  any  specific  way  by  the  liver.  On  this 
point  opinions  have  differed  greatly.  After  a  meal  the  amino- 
acids  in  the  blood  and  in  the  tissues  generally  are  increased  in 
amount,  and  this  fact  would  indicate  that  these  substances  pass 
through  the  liver  without  undergoing  any  intermediate  metabolism. 
They  are  disseminated  over  the  body  at  large  and  undergo  their 
subsequent  metabolic  changes  in  the  several  tissues;  but  it  is 
probable,  as  is  explained  below,  that  one  stage  in  the  metabolism  of 
some  of  these  amino-acids  may  be  carried  out  especially  in  the  liver. 

Concerning  the  further  history  of  the  amino-acids  or  the  nature 
of  the  processes  of  protein  metabolism  in  the  tissues  there  have 
been  many  different  theories  and  points  of  view.*  It  would  be 
confusing  to  give  summaries  of  these  diverging  theories,  and  it  may 
suffice  to  indicate  briefly  the  conception  that  seems  to  be  most 
in  accord  with  recent  work.  It  may  be  accepted  as  a  necessary 
conclusion  that  some  of  these  amino-acids  are  recombined  by  syn- 
thetic processes  to  form  organized  protein,  of  the  kind  character- 
izing the  particular  tissue,  for  only  in  this  way  can  we  understand 
how  the  wear  and  tear  of  the  tissue  is  replaced  or  how  new  protein 
is  made  in  the  growing  animal.  Whether  this  synthetic  combina- 
tion is  effected  by  endo-enzymes  or  under  the  influence  of  the  living 
protein  of  the  cells  cannot  be  stated,  but  we  may  assume  that  the 
several  amino-acids  which  enter  into  the  structure  of  that  particular 

*  For  a  review  of  these  theories  consult  Mendel,  "Ergebnisse  der  Phys- 
iologie,"  11,  418,  1911. 


904  NUTRITION    AND    HEAT    REGULATION. 

kind  of  protein  are  combined  in  general  after  the  manner  of  the 
formation  of  polypeptids  (p.  1026).  This  portion  of  the  nitrogenous 
material  that  is  used  to  replace  tissue  waste  or  to  provide  new  tissue 
has  long  been  designated  as  tissue  protein,  and  in  the  adult  ani- 
mal a  relatively  small  fraction  of  the  nitrogenous  food  may  suffice 
for  this  purpose.  Considering  the  varying  composition  of  proteins 
in  amino-acids  it  is  probable  that  in  this  matter  of  replacing  tissue 
or  providing  material  for  new  tissue  some  protein  food-stuffs 
may  be  more  effective  than  others,  since  they  may  contain  more 
nearly  the  particular  proportions  of  amino-acids  essential  in  the 
construction  of  human  tissue  protein.  Experiments  seem  to  bear 
out  this  a  priori  probability.  Thomas,*  in  experiments  upon  him- 
self, found  in  general  that  the  proteins  furnished  by  animal  foods 
are  more  efficient  in  this  respect  than  those  obtained  from  vege- 
table foods.  Designating  the  efficiency  of  cows'  milk  as  100,  he 
finds  that  ox  meat  has  a  value  of  104;  fish,  95;  crab  meat,  79; 
peas,  56;  wheat  flour,  40;  cornmeal,  30.  These  numbers  represent 
what  he  calls  the  biologic  value  of  the  several  sources  of  protein 
commonly  used  in  our  diets  The  amino-acids  not  employed  in 
the  construction  of  tissue  protein  are  utilized  presumably  as  a 
source  of  energy.  When  the  protein  food  is  large  in  amount 
the  greater  portion  no  doubt  fulfils  this  function.  When  the 
protein  food  is  reduced  to  minimal  proportions  the  amount  left  for 
energy  purposes  is  diminished  correspondingly.  It  will  be  shown 
later  that  ordinarily  we  eat  more  protein  daily  than  is  required  to 
cover  our  tissue  wastes,  that  is,  to  provide  the  necessary  tissue- 
protein,  so  that  on  a  customary  diet  it  is  probable  that  a  good  pro- 
portion of  the  products  of  protein-digestion  is  used  to  furnish  energy 
rather  than  to  construct  tissue.  The  further  history  of  the  por- 
tion used  for  energy  purposes  is  not  wholly  known,  but  the  main 
point  is  that  the  amino-acids  constituting  this  portion  undergo 
deaminization.  The  NH2  group  is  split  off  to  form  ammonia  that 
is  subsequently  converted  to  urea  and  excreted,  while  the  organic 
acid  radicle  which  is  left  is  oxidized  to  furnish  energy  or  is  built  into 
sugar  or  fat  and  oxidized  at  some  later  period.  This  portion  of  the 
amino-acid,  therefore,  may  be  regarded  as  a  source  of  energy 
entirely  equivalent  to  that  furnished  by  the  non-protein  elements 
of  the  food,  the  carbohydrates  and  the  fats.  If  we  grasp  the  funda- 
mental idea  that  from  the  supply  of  amino-acids  furnished  to  the 
tissues  by  the  digested  food-proteins  certain  ones  are  selected  to 
construct  the  peculiar  tissue-protein  of  the  animal,  so  far  as  this  is 
required  for  growth  or  tissue-repair,  then  it  is  evident  that  the 
balance  is  not  needed  as  nitrogenous  material,  and  its  nitrogen  is 
removed  by  deaminization,  while  the  remainder  of  the  molecule 

*  Quoted  from  Lusk,  "Science  of  Nutrition,"  3d  ed.,  1917,  p.  371. 


GENERAL    METHODS — HISTORY    OF    PROTEIN    FOOD.  905 

serves  for  purposes  of  energy-supply,  just  as  the  non-nitrogenous 
food-stuffs  might  do.  We  may  suppose  that  it  is  the  excess  amino- 
acids  not  used  in  tissue  construction  that  undergo  this  fate. 

A  third  possibility  in  regard  to  the  fate  of  the  amino-acids,  or  ratter  the 
absorbed  products  of  protein  digestion,  has  been  discussed  more  or  less  at 
times  in  physiology.  In  addition  to  the  portion  that  is  applied  to  the  repair 
or  construction  of  tissue,  it  has  been  held  that  another  portion  may  be  syn- 
thesized to  a  form  of  non-organized  or  non-living  protein  held  as  a  sort  of 
storage  supply  in  the  liquids  of  the  body,  that  is,  the  blood  and  lymph.  It 
has  been  supposed  that  this  material  is  called  upon  first  in  fasting  or  starva- 
tion, and  that  it  constitutes  an  easily  used  form  of  protein  food  of  limited 
amount  which  is  designated  as  circulating  or  storage  protein.  Our  knowledge 
in  regard  to  this  material  is  quite  indefinite  at  present.  Certainly  none  of  the 
known  proteins  of  blood  or  lymph  seem  to  discharge  this  function. 

It  was  supposed  formerly  that  the  process  of  deaminization 
of  the  excess  of  the  ammo-bodies  is  accomplished  mainly  in  the 
liver,  but  this  view  has  been  brought  into  question  lately.* 
That  the  process  takes  place  in  the  body  is  beyond  doubt,  and 
it  is  likely  that  the  liver  shares  in  this  activity  even  if  it  is  not 
the  chief  tissue  concerned.  That  the  body  is  able  to  build  up 
its  own  protein  from  a  mixture  of  amino-acids,  such  as  is  pro- 
duced in  a  complete  digestive  hydrolysis  of  protein,  has  been 
demonstrated  beyond  doubt  by  feeding  experiments  in  which 
the  nitrogenous  food  was  all  supplied  in  the  form  of  such  a  mix- 
ture. The  first  experiments  of  this  kind  were  made  by  Loewi.f 
He  fed  dogs  on  a  diet  consisting  of  fats,  carbohydrates,  and  protein 
which  had  been  submitted  previously  to  a  prolonged  pancreatic 
digestion  until  it  was  completely  hydrolyzed.  On  this  diet  the 
animal  was  maintained  in  nitrogen-equilibrium.  This  experiment 
has  been  verified  and  extended  by  others  on  man  as  well  as  upon 
dogs,  and  indeed  Abderhalden  and  Rona  report  that  they  have 
been  able  to  keep  a  dog  not  only  in  nitrogen-equilibrium  but  with 
a  plus  balance  of  nitrogen  when  fed  on  the  split  products  of  meat 
alone,  without  addition  of  fats  or  carbohydrates.  This  last 
experiment  would  indicate  that  the  amino-bodies  not  only  give  to 
the  body  material  from  which  it  can  reconstruct  its  own  protein, 
but  they  furnish  also  a  usable  source  of  energy  for  the  body 
needs,  a  result  which  we  can  understand  on  the  hypothesis  men- 
tioned above,  according  to  which  the  amino-acids,  after  removal 
of  the  NH2  group,  furnish  an  organic  acid  residue  capable  of  further 
oxidation  or  of  synthesis  to  fats  or  carbohydrates. 

We  may  accept  as  a  clear  result  of  modern  investigation  that  the  body  is 
capable  of  building  up  its  protein  from  such  relatively  simple  substances  as 
the  amino-acids,  in  fact  the  evidence  goes  to  show  that  normally  it  is  from  these 

*  See  Fiske  and  Summer,  "Journal  of  Biological  Chemistry,"  18,  285,  1914. 
t  For  the  literature  consult  Liithje,   "Ergebnisse  der  Physiologic, "  vii, 
1908,  or  Abderhalden,  "Synthese  der  Zellbausteine,"  etc.,  1912. 


906  NUTRITION    AND    HEAT    REGULATION. 

amino-acids  that  the  nitrogenous  material  of  the  body  protein  is  derived. 
This  striking  result  has  led  investigators  to  test  whether  the  body  may  utilize 
sources  of  nitrogen  of  even  simpler  construction,  such,  for  example,  as  the 
organic  or  inorganic  salts  of  ammonia.  It  has  long  been  known  that  the  plant 
organism  utilizes  inorganic  forms  of  nitrogen,  such  as  the  ammonia  salts  or  the 
nitrates,  in  building  up  its  protein,  and  it  has  long  been  believed  that  the 
animal  protoplasm  is  not  able  to  utilize  these  salts  in  the  same  way,  that,  in 
other  words,  its  processes  of  synthesis  so  far  as  the  protein  material  is  concerned 
are  more  limited  than  in  the  plants.  It  has  been  taught  universally  that  ani- 
mals for  the  construction  of  new  tissue  must  have  their  nitrogenous  food  in  the 
form  of  protein,  or,  a  recent  addition,  in  the  form  of  the  split-products  of  pro- 
tein. Several  observers  report  (see  Grafe,  "Zeitschrift  f.  physiolog.  chemie.," 
78,  485,  1912)  that  when  animals  are  fed  upon  an  abundance  of  carbohydrate 
food  together  with  some  ammonia  salt,  such  as  ammonium  citrate,  acetate,  or 
carbonate,  they  may  maintain  a  positive  nitrogen  balance  for  long  periods. 
In  the  metabolism  of  the  amino-acids  in  the  body  it  is  recognized  that  by 
deaminization  and  oxidation  an  oxyacid  or  ketonic  acid  may  be  produced, 
and  it  is  suggested  that  this  process  may  be  reversed,  that  an  oxyacid,  lactic 
acid  formed  from  sugar,  may  combine  with  ammonia,  furnished  by  an  am- 
monia salt  in  the  diet,  to  produce  an  amino-acid,  according  to  the  reversible 
equation — 

CH3CHNH2COOH  +  H2O  U  CH3CHOHCOOH  +  NH3. 

If  this  is  true,  then  it  might  follow  that  an  inorganic  salt  of  ammonia  could 
under  certain  conditions  supply  the  nitrogen  necessary  for  the  construction 
of  body-proteins,  or  at  least  for  some  of  the  amino-acids  concerned  in  this 
synthesis.  The  matter  is  still  under  investigation.  Some  observers  (Under- 
bill and  Goldschmidt,  "Journal  of  Biological  Chemistry,"  15,  341,  1913) 
state  that  there  is  a  difference  in  this  respect  between  the  inorganic  and 
organic  salts  of  ammonia  so  far  as  the  animal  body  is  concerned.  With  the 
inorganic  salts  (ammonium  chlorid)  and  non-protein  food  no  evidence  can 
be  obtained  of  the  utilization  of  the  ammonia.  With  the  organic  salts,  on  the 
contrary  (ammonium  citrate  or  acetate),  there  is  a  marked  decrease  in  the 
nitrogen  loss  when  the  animal  receives  in  addition  only  non-protein  food. 
Other  observers,  however,  doubt  the  application  of  these  results  to  normal 
nutrition.  It  is  possible,  for  example,  that  the  utilization  of  the  ammonia 
salts  may  be  effected  indirectly  through  bacterial  action  in  the  intestines. 

The  Amount  of  Protein  Necessary  for  Normal  Nutrition. — • 

As  was  stated  above,  nitrogen  equilibrium  may  be  maintained  on 
different  amounts  of  protein  food.  It  is  important,  irom  a 
scientific  and  from  an  economic  standpoint,  to  determine  the  low 
limit  for  this  equilibrium  and  to  ascertain  whether,  for  the  purpose 
of  the  best  as  well  as  the  most  economical  nutrition,  this  low 
limit  is  as  good  as  or  preferable  to  a  higher  amount  of  protein  in 
the  diet.  Examination  of  the  dietaries  of  civilized  races  shows 
that,  on  the  average,  100  to  120  gms.  of  protein  are  used  daily  by 
an  adult  man.  Voit  gives  118  gms.  of  protein  as  the  average 
daily  consumption.  A  variable  portion  of  this  amount  passes 
into  the  feces  in  undigested  form,  but  we  may  assume  that  about 
100  to  105  gms.  are  absorbed  and  actually  metabolized  in  the  body. 
If  we  take  into  account  the  weight  of  the  body,  this  amount  of 
protein  may  be  estimated  as  equivalent  in  round  numbers  to 
1.5  gms.  of  protein  (or  0.23  gm.  nitrogen)  per  kilogram  of  body- 
In  recent  years  serious  attempts  have  been  made  to 


GENERAL    METHODS — HISTORY    OF    PROTEIN    FOOD.  907 

ascertain  how  low  this  daily  quota  of  protein  may  be  reduced 
without  destroying  nitrogen  equilibrium  or  injuring  the  effective- 
ness of  the  body  for  muscular  or  mental  work.  Siven  was  able 
for  short  periods  to  reduce  his  daily  diet"  of  protein  to  as  little  as 
0.5  gm.  (0.08  gm.  N.)  per  kilo  of  body  weight,  but  probably  the 
most  important  experiments  of  this  kind  are  those  carried  out 
by  Chittenden.*  In  this  work  the  experiments  were  continued 
over  long  periods  of  time,  and  were  made  upon  three  different 
groups  of  men,  five  university  teachers,  a  detail  of  thirteen  men 
from  the  Hospital  Corps  of  the  Army,  and  eight  university  students 
classed  as  athletes.  The  general  result  of  the  investigation 
showed  that  the  body  can  be  maintained  in  protein  equilibrium 
and  in  a  normal  state  of  efficiency  upon  a  diet  containing  only 
30  to  50  gms.  of  protein  per  day,  according  to  the  weight  of  the 
individual — or,  expressed  in  more  general  terms,  the  daily  quota 
of  protein  per  kilo  of  weight  may  be  reduced  from  1.5  gms. 
(0.23  gm.  N.)  to  about  one-half,  that  is,  0.75  gm.  of  protein  or 
0.12  gm.  of  nitrogen  per  kilo.  This  general  result  has  been 
confirmed  on  a  large  scale  by  the  studies  made  by  McCayf  of 
the  metabolism  of  the  Bengalis  of  India.  He  finds  that  the 
average  Bengali  metabolizes  in  his  body,  so  far  as  may  be  judged 
from  the  nitrogen  excreted  in  the  urine,  only  about  37.5  gms.  of 
protein  daily,  corresponding  to  a  consumption  per  kilo  of  0.7  gm. 
of  protein  or  0.113  gm.  of  nitrogen.  A  corresponding  average 
amount  of  protein  is,  of  course,  eaten  daily,  and  on  this  low  pro- 
tein diet  they  exist  in  apparent  health.  RubnerJ  also  empha- 
sizes the  fact  that  milk,  which  forms  the  sole  diet  of  the  infant,  is 
a  protein  poor  food.  The  usual  daily  diet  of  the  adult  has  a  heat 
value  of  from  2400  to  3000  calories  (see  p.  952).  Of  this  total 
heat  value  the  protein  food  in  the  diets  usually  recommended 
forms  about  15  to  20  per  cent.  In  milk,  however,  according  to 
Rubner's  estimates,  the  protein  constitutes  only  about  10  per 
cent,  of  the  total  heat  value.  As  the  result  of  these  and  similar 
investigations,  the  practical  question  presents  itself  as  to  what 
constitutes  the  optimum  daily  quota  of  protein.  If  the  body  can 
be  kept  in  good  condition  upon  0.75  gm.  per  kilo  per  day,  will  an 
ingest  ion  of  more  than  this,  say  twice  as  much,  prove  injurious 
or  beneficial  or  indifferent  to  the  body?  Outside  its  hygienic 
aspect  the  question  is  important  from  an  economical  standpoint, 

*  Consult  Chittenden,  "Physiological  Economy  in  Nutrition,"  New  York, 
1905,  for  discussion  and  literature.  See  also  Hinhede,  "Skandinavisches  Ar- 
chiv.  f.  Physiol.,"  30,  97,  1913. 

t  McCay,  "The  Metabolism  of  the  Bengalis,  Calcutta,"  1908.  (Scientific 
Memoirs,  Medical  Department  Government  of  India,  No.  34.)  Also  later 
report  upon  Jail  Dietaries,  ibid.,  No.  37,  1910. 

t  Rubner,  "Das  Problem  des  Lebensdauer,"  1908;  Cohnheim,  "Die  Phys- 
iologic der  Verdauung  u.  Ernahrung,"  1908. 


908  NUTRITION    AND    HEAT    REGULATION. 

since  the  proteins  are  the  most  expensive  foods,  and  in  the  feeding 
of  large  masses  of  individuals — armies,  schools,  asylums,  etc. — 
it  is  not  desirable  to  waste  money  on  protein  food  if  it  is  not 
needed.  The  full  and  satisfactory  answer  to  this  question  must 
be  deferred  until  more  experience  is  obtained.  The  report  upon 
the  Bengalis,  noted  above,  would  seem  at  first  to  constitute  a 
satisfactory  demonstration  of  the  practicability  of  a  low  protein 
diet,  but  McCay  states  that  the  Bengali  is  inferior  physically  to 
the  average  European,  and  is  particularly  deficient  in  capacity 
for  muscular  work,  and  he  is  inclined  to  attribute  this  inferiority 
to  the  diet.  Moreover,  the  Bengali  is  quite  susceptible  to  kidney 
troubles,  a  fact  which  seems  to  destroy  one  prediction  often 
made  by  those  who  advocate  a  low  protein  diet,  namely,  that  the 
smaller  amount  of  work  thus  thrown  on  the  kidneys  would  result 
in  a  diminution  of  diseases  of  the  kidney.  The  newer  conceptions 
in  regard  to  the  digestion  and  nutritive  history  of  the  protein 
foods  certainly  seem  to  favor  the  adoption  of  a  low  protein  diet. 
If  protein  is  eaten  in  excess  of  the  real  assimilation  needs  of  the 
tissues,  all  the  excess,  so  far  as  we  can  see,  might  just  as  well  be 
substituted  by  carbohydrate  or  by  carbohydrate  and  fat.  The 
excess  nitrogen  thus  eaten  appears  to  be  so  much  useless  ballast 
which  the  body  very  promptly  gets  rid  of,  although  it  must  be 
remembered  that  the  ammonia  formed  in  the  process  of  deaminiza- 
tion  plays  a  most  useful  role  in  neutralizing  the  acids  formed  in  the 
body.  The  uncertain  point,  however,  is  what  constitutes  the  assimi- 
lation need  of  the  tissues.  The  experiments  given  above  would  place 
this  need  very  low,  according  to  the  lowest  estimate  at  about  5  per 
cent,  of  the  total  energy  value  of  the  food.  That  is  to  say,  if  the 
daily  diet  contains  heat  energy  equivalent  to  2400  calories,  only 
5  per  cent,  of  this,  120  calories,  needs  to  be  in  the  form  of  protein, 
an  estimate  which  would  bring  the  protein  to  about  30  gm. 
daily.  Many  objections  have  been  urged  against  the  attempt  to 
apply  this  apparently  logical  conclusion  to  public  dietaries.  We 
are  reminded  that  our  knowledge  of  the  details  of  the  metabolism 
of  protein  is  very  incomplete,  and  it  is  not  certain  yet  that  in 
the  long  run  a  low  protein  diet  would  be  entirely  without  injury. 
Emphasis  has  been  laid  also  upon  the  importance  of  providing 
what  Meltzer  has  named  a  "f actor  of  safety,"  that  is  to  say,  a 
certain  margin  beyond  a  bare  sufficiency  which  will  be  a  reserve 
against  unusual  demands,  but  this  objection  simply  serves  to  re- 
state the  question.  If  a  man  is  accustomed  to  eat  100  gm.  of 
protein  daily  and  science  demonstrates  that  he  can  maintain  a 
nitrogen  equilibrium  on  30  gm.,  does  a  reasonable  factor  of  safety 
require  the  use  of  the  additional  70  gm.,  or  would  perhaps  a 
total  of  50  or  60  gm.  per  day  meet  every  requirement?  It  seems 


GENERAL  METHODS —HISTORY  OF  PROTEIN  FOOD.     909 

obvious  that  we  must  find  out  the  truth  in  this  matter  by  obser- 
vation and  experiment.  There  is  one  consideration  that  should 
induce  us  to  be  cautious  in  making  a  radical  change  in  the  diet- 
ing of  collections  of  individuals,  such  as  armies,  institutions, 
etc.,  and  that  is,  that  our  instinctive  appetite  seems  to  lead  us 
to  seek  the  higher  protein  diet.  We  know  very  little,  indeed,  about 
the  mechanism  of  these  appetites,  but,  as  a  matter  of  fact,  they 
and  not  the  results  of  science  control  the  amount  and  kind  of 
food  that  we  eat.  Science 'is  rapidly  gaining  information  that 
enables  us  to  guide  or  control  the  appetite  for  food  in  a  conscious 
and  reasonable  way,  but  at  present  our  knowledge  is  not  sufficient 
to  warrant  disregarding  the  bodily  sensations  when,  as  in  the  case 
in  question,  they  seem  to  cause  a  similar  reaction  in  normal  men 
under  varying  conditions.  Studies  of  dietaries  seem  to  show  that 
mankind,  left  to  the  guidance  of  the  natural  appetites,  has  always, 
when  possible,  adopted  the  high  protein  level  of  90  to  100  gm.  per 
day.  Indeed,  the  uniformity  with  which  this  level  has  been  un- 
consciously maintained  is  a  striking  fact.  Among  the  rich  as  well 
as  the  poor,  and  in  races  very  differently  placed  as  regards  quantity 
of  available  food,  substantially  the  same  amount  of  protein  (80  to 
100  gms.)  is  consumed  daily  by  each  individual.  The  element  of 
the  diet  which  varies  most  widely,  as  Cohnheim  points  out  in  an 
interesting  discussion  of  this  question,  is  the  non-protein,  particu- 
larly the  carbohydrate  material.  Those  who  are  obliged  to  do 
much  muscular  work  to  earn  a  living  or  for  the  sake  of  pleasure 
(sports,  athletics)  add  to  their  daily  quota  of  protein  an  excess  of 
carbohydrate  food  to  furnish  the  requisite  energy.  On  the  con- 
trary, those  whose  daily  life  requires  but  little  muscular  exertion 
cut  down  the  carbohydrates  and  fats,  and  make  their  diet  relatively 
but  not  absolutely  richer  in  protein.  That  mankind  has  made  a 
mistake  in  adopting  instinctively  the  higher  protein  level  can  hardly 
be  claimed  on  the  basis  of  our  present  knowledge. 

Nutritive  Value  of  Different  Proteins. — If  we  consider  all  the 
different  kinds  of  animal  and  vegetable  foods  it  is  evident  that 
a  great  variety  of  proteins  must  be  utilized  in  nutrition.  For- 
merly, it  was  the  belief  that  all  these  different  proteins  (with  the 
exception  perhaps  of  gelatin)  have  an  equal  nutritive  value.  But 
the  knowledge  that  the  composition  of  these  proteins  varies  hi 
regard  to  the  number  and  character  of  their  constituent  amino- 
bodies,  and  the  fact  that  each  animal  out  of  the  complex  offered  to 
it  in  its  food  selects  certain  amino-acids  in  certain  proportions  from 
which  to  reconstruct  its  own  peculiar  body-proteins,  suggest  natu- 
rally the  thought  that  the  different  proteins  may  have  different 
values  hi  nutrition.  Experiments  have  demonstrated,  in  fact,  that 
this  is  the  case.  From  the  standpoint  of  supplying  the  energy 


910  NUTRITION    AND    HEAT    REGULATION. 

needs  of  the  body,  the  proteins  are,  so  far  as  we  know,  pretty  much 
of  the  same  value,  but  from  the  standpoint  of  supplying  material  for 
tissue  construction  they  may  differ  a  great  deal  (see  p.  955).  Some 
proteins,  when  fed  together  with  an  adequate  supply  of  non-pro- 
tein material  and  water  and  salts,  furnish  all  the  nitrogenous  com- 
pounds necessary  for  maintenance  and  growth;  others  under  the 
same  conditions  fail  to  support  growth  or  maintenance,  or  both. 
The  former  group  may  be  spoken  of  as  complete  or  adequate  pro- 
teins, the  latter  as  incomplete  or  inadequate  proteins.  The  differ- 
ence between  the  two  kinds  seems  to  lie  in  the  character  of  the 
amino-acids  of  which  they  are  composed.  Some  of  the  amino- 
acids  which  the  body  tissues  need  for  repair  or  growth  may  be  made 
in  the  body  from  other  amino-acids,  glycin,  for  example,  but  others 
apparently  must  be  furnished  in  the  protein  of  the  food,  and  if  they 
are  lacking,  tissue  construction  is  not  possible. 

It  has  long  been  known  that  gelatin  is  an  inadequate  protein 
in  this  sense.  It  is  digested  easily  and  absorbed  and  eventu- 
ally undergoes  oxidation  in  the  body  with  the  production  of  carbon 
dioxid,  water,  and  urea.  The  energy  liberated  by  this  metabolism 
is  utilized  no  doubt  in  the  body,  and  the  gelatin  constitutes  an 
"energy-food"  similar  in  a  general  way  to  the  carbohydrates  and 
fats,  although  its  various  amino-acids  must  give  it  to  some  extent 
a  special  significance.  The  important  point  in  this  connection  is 
that  gelatin  alone  or  with  carbohydrates  or  fats  does  not  suffice  to 
maintain  nitrogen  equilibrium.  It  does  not  supply  fully  the 
nitrogenous  material  needed  for  the  repair  of  tissue.  This  defi- 
ciency is  explained  by  the  fact  that  in  the  composition  of  the  gelatin 
certain  important  amino-acids  are  lacking,  tryptophan  (indolami-. 
nopropionic  acid),  tyrosin  (oxyphenylaminopropionic  acid),  and 
cystein  (thioaminopropionic  acid).  It  is  stated  that  if  a  dog  is  fed 
upon  a  diet  in  which  the  nitrogenous  material  is  represented  only 
by  the  split  products  of  a  gelatin-hydrolysis  he  will  show  a  minus 
nitrogen  balance,  but  if  the  above-named  missing  amino-acids  are 
added,  particularly  the  tryptophan,  he  will  then  maintain  his 
nitrogen  equilibrium. 

The  history  of  gelatin  as  a  food  is  very  interesting  and,  indeed,  instructive, 
since  it  serves  or  should  serve  as  a  warning  against  a  premature  application 
of  the  results  of  scientific  investigation.  A  condensed  account  of  the  subject 
is  given  by  Voit  in  Hermann's  Handbuch  der  Physiologie,  vol.  vi.,  p.  396. 
It  would  seem  that  on  account  of  the  high  nitrogen  content  of  the  gelatin,  and 
the  fact  that  it  is  soluble,  there  was  a  tendency  to  attribute  to  it  an  unusual 
nutritive  value.  The  fact,  too,  that  the  gelatin  could  be  obtained  from  bones 
which  otherwise  were  burned  or  thrown  away  was  important  hi  suggesting 
a  means  for  the  economical  feeding  of  the  poor.  The  matter  was  inquired 
into  by  a  committee  during  the  French  Revolution  and  subsequently  by  a 
commission  of  the  French  Academy,  who  made  favorable  reports.  The  success 
of  d'Arcet,  in  making  gelatin  economically  by  a  new  process,  led  the  Philan- 
thropic Society  of  Paris  to  request  the  Academy  of  Medicine  to  investigate 


GENERAL    METHODS HISTORY    OF    PROTEIN    FOOD.  911 

whether  gelatin  is  really  a  nutritious  and  healthy  food.  The  Academy 
appointed  a  commission  for  the  purpose  and  the  report  of  this  commission 
published  in  the  Annales  de  Chimie,  vol.  92,  1814,  was  most  enthusiastic. 
Ihey  recommended  gelatin  as  a  most  nutritious  and  healthful  food,  when  its 
natural  insipidity  was  corrected  by  the  addition  of  salts  and  savory  herbs. 
On  the  basis  of  this  report  the  article  was  largely  used  in  the  nourishment  of 
hospital  patients,  but  in  course  of  time  complaints  became  so  emphatic  that 
doubt  was  again  raised  as  to  its  real  value.  In  fact,  a  reaction  set  in.  The 
second  gelatin  commission  of  the  French  Academy,  1841,  a  commission  of 
the  Netherland's  Institute,  1844,  and  a  report  from  the  Academy  of  Medicine, 
Paris,  1850,  all  condemned  gelatin  as  useless  from  the  standpoint  of  nourish- 
ment, and  as  injurious  rather  than  beneficial.  Thus,  as  so  often  happens, 
public  opinion  oscillated  from  one  extreme  to  the  other.  The  true  value 
of  the  gelatin,  as  we  understand  it  to-day,  was  established  by  Voit's  experi- 
ments, but  it  is  evident  that  something  remains  to  be  explained.  It  is  not 
clear  why  it  cannot  be  borne  better  in  a  diet  when  used  in  quantity. 

Most  suggestive  results  on  this  question  of  the  nutritive  values 
of  the  different  proteins  have  been  obtained  in  a  series  of  experi- 
ments reported  by  Osborne  and  Mendel.*  These  observers  made 
use  of  rats,  which  were  fed  with  a  suitable  mixture  of  inorganic 
salts,  carbohydrate,  fats,  and  some  single  protein  representing  the 
sole  form  in  which  nitrogenous  material  was  supplied.  They 
found  that  in  addition  to  gelatin  the  protein  zein  obtained  from 
maize,  which  is  deficient  in  the  amino-acids,  tryptophan,  lysin,  and 
glycin,  is  also  an  inadequate  or  incomplete  protein.  Gliadin  and 
hordein  which  are  alcohol  soluble  proteins  obtained  from  wheat, 
rye,  and  barley  when  fed  alone  sufficed  for  maintenance,  but  not  for 
growth.  A  young  rat  fed  upon  gliadin  alone  ceased  to  grow,  but 
did  not  lose  in  weight,  although  the  power  of  growth  was  not  lost, 
since  at  any  time  satisfactory  growth  could  be  re-established  by 
substituting  a  suitable  dietary  for  the  gliadin  mixture.  By  the 
same  method  it  was  shown  that  the  leguminous  proteins  when 
fed  alone  are  inadequate  for  growth,  although  in  this  case  appa- 
rently the  defect  is  not  due  to  lack  of  necessary  amino-acids,  but 
to  some  other  undetermined  cause.  There  are,  however,  many 
single  proteins  which,  when  fed  alone,  seem  to  be  entirely  sufficient 
to  provide  all  the  necessary  nitrogenous  material  for  maintenance 
and  growth.  Such  proteins  are,  for  example,  casein  from  milk, 
edestin  from  hemp  seed,  glutein  from  wheat,  lactalbumin  from 
milk,  vitellin,  etc.  Experiments  of  this  kind  bring  out  in  a  decisive 
way  the  important  fundamental  fact  that  proteins  differ  among 
themselves  in  regard  to  their  utility  in  furnishing  material  for  cell 
repair  and  growth,  and  the  evidence  at  hand  goes  to  show  that  the 
qualitative  differences  are  dependent  upon  variations  in  the  amino- 
acids  of  which  they  are  composed.  A  protein-like  zein  is  inade- 
quate because  it  is  lacking  in  certain  essential  amino-acids,  namely, 

*  Osborne  and  Mendel,  "Carnegie  Institution  of  Washington,  Publication 
156,"  parts  I  and  II,  1911;  also  "Journal  of  Biological  Chemistry,"  12,  473, 
1912;  13,  233,  1912,  and  15,  311,  1913. 


912  NUTRITION    AND    HEAT    REGULATION. 

tryptophan  and  lysin.  Gliadin  and  hordein  are  also  inadequate, 
so  far  as  growth  is  concerned,  because  they  lack  lysin.  If  the  miss- 
ing amino-acids  are  supplied,  either  directly  or  by  using  other  pro- 
teins, then  the  functions  of  maintenance  and  growth  are  adequately 
supported.  In  an  ordinary  diet  we  do  not,  of  course,  use  single 
proteins.  Our  foods  contain  a  variety  of  proteins,  and  it  is  not  at  all 
probable  that  a  natural  diet  would  be  lacking  entirely  in  any  of  the 
essential  building-stones.  Work  of  the  kind  described  above  helps 
to  bring  out  important  data  in  regard  to  the  particular  role  played 
by  the  different  amino-acids.  One  evident  outcome  of  the  work 
reported  seems  to  be  that  some  of  these  amino-acids,  glycin,  for 
example,  may  be  formed  de  novo  in  the  animal  body  by  synthetic 
processes  or  by  transmutation  of  other  amino-acids,  while  others, 
such  as  tryptophan,  lysin,  and  probably  tyrosin,  cannot  be  so  man- 
ufactured, but  have  to  be  supplied  from  without  in  the  protein  food. 
From  this  point  of  view  a  protein  may  be  adequate  for  nutrition 
even  though  it  contains  no  glycin,  since  this  latter  amino-acid  can 
be  constructed  within  the  body  from  other  amino-acids.  A  pro- 
tein that  lacks  tryptophan,  tyrosin,  or  lysin  is  inadequate  if  supplied 
alone  in  the  diet,  since  these  building  stones  are  essential  in  the 
construction  of  tissue  protein  and  cannot  be  formed  within  the 
body  itself.  The  amino-acids  also  show  differences  in  nutritive 
value  when  they  are  deaminized  and  used  as  sources  of  energy, 
rather  than  as  building  stones  for  tissue  protein.  This  conclusion 
seems  justified  by  experiments  which  have  shown  that  certain 
of  these  amino-acids,  for  example,  glycin,  alanin,  aspartic  acid, 
glutaminic  acid,  prolin  and  arginin,  serve  as  a  source  of  sugar  within 
the  body;  while  others,  as  leucin,  lysin,  tyrosin,  and  tryptophan, 
do  not.  Some  of  these  latter,  in  fact,  in  their  metabolism  may  yield 
oxj^butyric  acid  after  the  manner  of  fats.  It  is  evident  from  these 
facts  that  one  important  result  to  be  expected  from  future  work 
is  the  history  of  each  of  the  known  amino-acids  furnished  by  the 
proteins  of  the  food.  Some  such  knowledge  will  be  necessary  in 
order  to  make  intelligent  use  of  these  substances  in  dietary  work. 

The  Unknown  Accessories  (Vitamines). — From  the  state- 
ments made  in  the  preceding  paragraphs  of  this  chapter  one  might 
conclude  that  a  perfect  food  would  be  one  which  supplied  enough 
non-protein  material  (fats  and  carbohydrates)  for  the  energy  needs, 
all  the  necessary  amino-acids,  and  the  essential  amounts  of  water 
and  inorganic  salts.  This  conclusion  has  been  made  doubtful  by 
much  recent  work,  which  tends  to  show  that  in  addition  to  these 
fundamental  requisites  there  are  certain  accessory  materials  that 
are  necessary,  either  because  they  play  some  essential  role  in  the 
syntheses  of  the  body  or  influence  in  some  more  indirect  way  the 
normal  direction  and  character  of  the  metabolism.  This  unex- 


GENERAL    METHODS — HISTORY    OF    PROTEIN    FOOD.  913 

pected  result  may  be  illustrated  best  by  reference  to  the  condition 
known  as  beriberi.  Beriberi  is  a  disease  that  occurs  chiefly  among 
oriental  nations  that  make  great  use  of  rice  as  a  food.  The  dis- 
ease takes  a  variety  of  forms,  but  the  characteristic  symptoms  are 
paralyses,  and  atrophy  and  contractures  of  the  limbs.  It  has  been 
shown  that  the  condition  is  caused  by  limiting  the  diet  exclusively 
or  mainly  to  polished  rice,  that  is,  to  rice  from  which  the  outer 
layers  of  the  grains  have  been  removed.  If  the  polishings  are 
restored  to  the  diet  the  condition  disappears,  or  if  other  materials, 
such  as  meat  and  barley,  are  used  with  the  polished  rice  the  disease 
does  not  occur.  The  interpretation  placed  upon  these  results 
is  that  the  polishings  contain  some  constituent  essential  to  body- 
metabolisms.  This  conclusion  has  been  much  strengthened  by 
experiments  on  fowls.  When  these  animals  are  fed  exclusively  on 
polished  rice  they  develop  a  condition  (polyneuritis)  similar  to 
beriberi  and  soon  die.  They  may  be  saved  by  adding  the  polishings 
to  the  diet  or  by  changing  the  diet.  Funk  has  shown  that  from 
the  polishings  of  rice,  and  from  many  other  of  the  ordinary  foods, 
there  can  be  isolated  a  relatively  simple  nitrogenous  base  which 
seems  to  resemble  in  structure  the  pyrimidin  bases  found  as  one 
component  of  nucleic  acid.*  He  designates  this  base  as  vitamine, 
and  experiments  show  that  when  administered  to  an  animal  or 
patient  exhibiting  the  symptoms  of  beriberi  these  symptoms  dis- 
appear. The  new  ideas  suggested  by  the  facts  known  in  regard 
to  beriberi  have  been  supplemented  by  much  interesting  work 
upon  the  effect  of  various  diets  upon  growth  and  maintenance, 
particularly  work  done  in  this  country  upon  white  rats  by  Osborne 
and  Mendel  f  and  by  McCollum  and  his  co-workers.  McCollum  { 
concludes  that  there  are  two,  and,  so  far  as  our  positive  knowledge 
goes,  only  two  of  these  essential  accessories  present  in  our  natural 
foodstuffs.  Inasmuch  as  their  chemical  nature  is  unknown  at 
present,  he  designates  them  provisionally  as  "fat-soluble  A"  and 
"water-soluble  B."  The  latter  corresponds  with  Funk's  vitamine. 
It  is  soluble  in  alcohol  as  well  as  water,  is  very  widely  distributed 
in  our  natural  foods,  but  is  absent  from  such  substances  as  purified 
sugar  or  starch.  It  is  the  lack  of  this  accessory  in  polished  rice 
which  makes  this  material,  when  taken  alone,  an  inadequate  diet. 
If  the  rice  is  used  together  with  other  foodstuffs,  animal  or  vege- 
table, the  water-soluble  accessory  is  provided  by  the  latter  and  the 

*  For  a  general  statement  with  literature  see  Funk,  "Ergebnisse  der  Phys- 
iologic," 13,  125,  1913. 

t  Osborne  and  Mendel,  "Journal  of  Biological  Chemistry,"  15,  311, 1913; 
16,  423,  1913,  and  Osborne  and  Wakeman,  ibid.>  21,  91,  1915. 

t  McCollum  and  Davis,  "Journal  of  Biological  Chemistry,"  23,  23,  1915; 
see  also  McCollum,  Harvey  Lecture,  1917,  "Journal  of  the  American  Medi- 
cal Association,  May  12,  1917. 

58 


914  NUTRITION    AND    HEAT    REGULATION. 

rice  furnishes  its  quota  of  carbohydrate  (and  protein)  for  the 
energy  needs  of  the  body.  According  to  this  conception-  a  diet 
made  up  mainly  or  exclusively  of  polished  rice  may  be  adequate 
from  an  energy  standpoint,  but  nevertheless  deficient  in  some  un- 
known particular.  Beriberi  or  polyneuritis  constitutes,  therefore, 
what  is  known  as  a  deficiency  disease.  The  second  accessory,  the 
fat-soluble  A,  is  equally  important.  In  our  natural  foods  it  is  found 
chiefly  in  animal  fats,  particularly  butter-fat  and  the  fat  of  the  egg- 
yolk,  and  in  the  foliage  of  plants.  The  usual  grains  in  cereals  con- 
tain insufficient  amounts  of  this  accessory,  but  it  occurs  in  larger 
quantity  in  the  leaves,  in  alfalfa,  for  example,  cabbage,  etc.  Young 
rats  fed  upon  a  diet  of  purified  protein,  starch  and  lard,  and  the 
proper  quota  of  inorganic  salts  do  not  grow  normally,  but  if  butter- 
fat  is  added  normal  growth  takes  place.  Chemical  examination 
of  this  fat-soluble  accessory  indicates  that  it  is  lacking  in  nitrogen 
and  phosphorus,  so  that  as  far  as  it  is  concerned  the  term  "vitamine" 
as  a  group  name  is  inappropriate.  As  stated  above,  feeding  experi- 
ments indicate  that  both  of  these  accessory  substances  are  essential 
to  normal  growth  and  maintenance.  The  part  that  they  play  in 
normal  metabolism  is  at  present  entirely  unknown.  Since  only 
very  small  amounts  are  needed  in  the  daily  diet,  it  has  been  sug- 
gested (Mendel)  that  they  act  after  the  manner  of  hormones. 

The  Specific  Dynamic  Action  of  Proteins. — This  somewhat 
indefinite  term  is  used  by  Rubner  to  designate  the  fact  that  pro- 
tein foods  seem  to  increase  the  metabolic  processes  of  the  body 
to  a  greater  extent  than  the  fats  or  carbohydrates.  This  pecu- 
liarity may  be  demonstrated,  for  instance,  in  the  case  of  an  animal 
that  has  been  starved  (eighteen  hours)  until  the  gastro-intestinal 
tract  is  free  from  food.  *  If  the  heat-  production  of  such  an  ani- 
mal is  determined  at  hourly  periods,  it  gives  an  index  of  what  may 
be  called  its  basal  metabolism  when  living  on  the  material  within 
its  body.  If  in  this  condition  the  animal  is  fed  with  carbohydrate 
(glucose)  there  will  be  an  increase  in  heat  production,  lasting  for 
three  or  four  hours,  which  may  amount  to  as  much  as  30  to  40 
per  cent.  Feeding  with  meat  or  with  some  of  the  amino-acids 
(glycin,  alanin)  causes  a  similar  but  more  marked  increase  in 
metabolism.  After  a  large  diet  of  meat  the  increase  may  amount 
to  as  much  as  90  per  cent.  This  effect  upon  the  metabolism  is 
exhibited  especially  by  proteins.  Many  explanations  of  it  have 
been  proposed,  but  recent  experiments  indicate  that  it  is  probably 
due  to  some  direct  stimulating  action  of  the  intermediary  acids, 
such  as  lactic  or  pyruvic  acid,  which  are  formed  during  the  further 
metabolism  of  the  amino-acids  in  the  body.  This  stimulating 
effect  of  proteins  may  furnish  a  physiological  explanation  of  the 
fact  that  in  hot  summer  weather  it  is  advisable  to  avoid  a  meat  diet. 

*  See  Lusk,  "Jour,  of  the  Amer.  Med.  Association,"  September  5,  1914. 


CHAPTER  XLVIII. 
NUTRITIVE  HISTORY  OF  CARBOHYDRATES  AND  FATS, 

The  Carbohydrate  Supply  of  the  Body. — The  available  carbo- 
hydrate material  of  the  body  consists  of  the  glycogen  found  in  the 
tissues,  especially  in  the  liver  (1  to  4  per  cent,  or  more)  and  mus- 
cles (0.5  per  cent.),  and  the  sugar  formed  from  this  glycogen  and 
present  constantly  hi  the  blood  to  the  amount  of  0.1  to  0.15  per 
jent.  The  supply  of  glycogen  under  normal  conditions  is  main- 
tained chiefly  by  the  carbohydrate  food.  As  was  explained  in  the 
section  on  Digestion,  the  starches,  sugars,  gums,  etc.,  which  con- 
stitute the  carbohydrate  foodstuffs  are  eventually  absorbed  into 
the  blood  as  simple  sugars,  chiefly  dextrose,  but  probably  also 
some  levulose  and  galactose.  These  simple  sugars  constitute 
the  important  glycogen  formers.  With  regard  to  the  proteins 
there  is  still  some  difference  of  opinion  as  to  whether  all  of  them 
are  capable  of  yielding  glycogen  to  the  body.  Accepting  the 
modern  view  that  the  proteins  in  digestion  are  split  into  their 
constituent  amino-bodies  the  question  of  the  relation  of  the  pro- 
tein-food to  sugar-formation  may  be  approached  most  readily  by 
investigating  the  effect  of  feeding  the  different  ammo-acids  sepa- 
rately. A  convenient  method  of  studying  this  point  is  to  feed  the 
amino-acids  to  dogs  rendered  diabetic  by  the  use  of  phlorhizin  (p. 
921).  In  such  animals  the  amino-acids,  if  converted  to  sugar,  will 
appear  hi  the  urine  as  sugar  and  can  be  detected  without  difficulty. 
Experiments  of  this  kind*  indicate  clearly  that  a  number  of  amino- 
acids  can  yield  sugar  hi  the  body,  for  example,  glycin,  alanin,  as- 
partic,  and  glutaminic  acids  (p.  831).  We  may  believe,  therefore, 
that  the  proteins  giving  rise  to  these  amino-acids  during  digestion 
may  serve  as  glycogen-formers.  The  store  of  glycogen  in  the  body 
is  about  equally  divided  between  the  liver  and  the  muscular  tissues, 
and  it  is  estimated  that  in  man  each  of  these  depots  may  contain, 
at  a  maximum,  about  150  gms.  The  regulation  of  the  supply  of 
sugar  to  the  blood  is  usually  attributed  to  the  liver.  This  regu- 
lation is  adjusted  so  that  the  percentage  of  sugar  in  the  blood  is 
kept  astonishingly  constant,  between  0.1  and  0.2  per  cent.,  not 

*  Lusk,  "American  Journal  of  Physiology,"  22,  174, 1908;  also  Ringer  and 
Lusk,  "Zeit.  f.  physiol.  chem.,  66,"  106,  1910. 

915 


916'  NUTRITION    AND    HEAT    REGULATION. 

only  during  the  conditions  of  ordinary  living,  but  under  such  an 
abnormal  condition  as  prolonged  starvation.  It  is  assumed  that 
this  constancy  of  composition  is  effected  mainly  by  an  enzyme 
formed  in  the  liver  cells,  which  converts  the  glycogen  to  dextrose 
in  proportion  as  the  sugar  of  the  blood  is  used  up  by  the  tissues, 
and,  as  was  stated  in  the  chapter  on  Internal  Secretions,  this 
process  of  glycogenolysis  may  be  accelerated  or  retarded  by  the 
action  of  hormones  arising  in  the  ductless  glands. 

Intermediary  Metabolism  of  Carbohydrates. — The  ordinary 
carbohydrates  of  our  food  after  the  completion  of  the  processes 
of  digestion  and  absorption,  glycogenesis,  and  glycogenolysis  are 
found  in  the  blood  in  the  form  of  dextrose,  and  in  this  form  they 
are  presented  to  the  tissues  for  utilization.  Eventually  the  dextrose 
undergoes  oxidation  to  carbon  dioxid  and  water,  but  it  can  hardly 
be  supposed  that  this  oxidation  takes  place  directly  upon  the 
sugar  molecule.  The  general  assumption  at  present  is  that  the 
dextrose  undergoes  cleavage  and  other  intermediary  reactions 
before  the  oxidation  takes  place.  Numerous  suggestions  have  been 
made  in  regard  to  the  nature  of  these  intermediary  changes,  but 
our  positive  knowledge  at  present  on  this  point  is  scanty  and 
unsatisfactory.  In  the  first  place  there  is  considerable  evidence 
that  this  normal  destructive  metabolism  does  not  take  place  with 
the  dextrose  itself.  This  substance  undergoes  certain  preparatory 
changes  in  which  the  internal  secretion  of  the  pancreas  is  concerned. 
We  know  that  if  the  pancreas  is  extirpated  the  whole  process  of 
the  metabolism  of  the  dextrose  is  suspended — the  dextrose  formed 
in  the  body  is  excreted  unchanged  in  the  urine.  Observations 
upon  isolated  organs,  such  as  the  heart,  perfused  with  solutions 
containing  dextrose  indicate  (Clark)  that  the  muscular  tissue  can- 
not readily  use  the  dextrose  unless  it  is  first  perfused  through  the 
pancreas.  What  this  preparatory  change  is  and  how  the  pancreas 
is  concerned  in  it  are  matters  for  speculation.  Since  dextrose  solu- 
tions when  submitted  to  perfusion  through  the  pancreas  and  the 
heart  undergo  a  diminution  in  optical  rotation  and  in  reducing 
power  (p.  898)  it  maybe  assumed  provisionally  that  the  simple  sugar 
is  condensed  into  some  form  of  polysaccharide,  and  it  is  possible,  of 
course,  that  other  substances  may  enter  into  this  synthesis.  The 
several  chemical  theories  that  have  been  suggested  to  explain  the 
processes  involved  in  the  oxidation  of  sugar  in  the  body  do  not  take 
account  of  this  preliminary  synthesis,  but  consider  the  metabolism 
as  beginning  with  the  dextrose  molecule.  There  is  much  evidence 
of  a  varied  character  which  indicates  that  in  tissue  activity  lactic 
acid  is  formed  from  the  dextrose.  The  dextrose  molecule  may  yield 
two  molecules  of  lactic  acid. 

6  =  2(C3H603) 


CARBOHYDRATES   AND    FATS.  917 

But  laboratory  investigations  suggest  that  this  conversion  takes 
place  indirectly  with  the  intermediate  formation  of  glyceric 
aldehyde  or  methylglyoxal,  or  both,  according  to  the  following 
reactions  : 


—  2H20   =  2(CH3COCOH) 

Dextrose.  Methylglyoxal. 

C6Hi2O6  —  H2O   =  CHaCOGOH  +  C2H3(OH)2COH 

Dextrose.  Methylglyoxal.  Glyceric  aldehyde. 

The  methylglyoxal  may  then  be  converted  to  lactic  acid. 
CH3COCOH  +  H2O   =  CH3CHOHCOOH 

Methylglyoxal.  Lactic  acid. 

Many  of  the  tissues  of  the  body  contain  an  enzyme  (glyox- 
ylase)*  capable  of  giving  this  reaction.  Regarding  the  further  fate 
of  the  lactic  acid  there  is  also  much  uncertainty.  The  usual  sup- 
position is  that  it  undergoes  oxidation  to  carbon  dioxid  and  water, 
but  the  steps  in  this  reaction  are  unknown.  According  to  one 
hypothesis  the  conversion  takes  place  through  a  series  of  reactions 
involving  reduction  and  cleavage  with  the  final  formation  of 
acetic  aldehyde  (CH3COH),  which  then  by  oxidation  is  converted 
to  acetic  acid,  formic  acid,  and  then  to  carbon  dioxid  and  water. 

Other  authors  find  no  experimental  evidence  that  lactic  acid 
itself  is  readily  oxidized,  and  assume  that  the  oxidation  takes  place 
in  the  methylglyoxal  stage.  Lactic  acid  by  dehydration  may  be 
changed  to  methylglyoxal,  and  this,  in  turn,  to  acetic  aldehyde, 
which  then  undergoes  oxidation  f.  On  the  other  hand,  it  must  be 
remembered  that  there  is  clear  evidence  that  the  body  can  convert 
lactic  acid  back  to  dextrose  probably  through  the  intermediate 
formation  of  methylglyoxal.  The  change  from  dextrose  to  lactic 
acid  is  a  reversible  reaction  which  in  the  body  can  take  place  in 
either  direction  according  to  conditions.  Under  normal  circum- 
stances the  carbohydrate  of  our  food  is  all  oxidized  in  a  few  hours, 
and  we  may  assume,  therefore,  that  usually  the  lactic  acid  and  other 
intermediary  products  follow  the  path  of  oxidation. 

At  least  one  other  interesting  product  formed  from  sugar 
has  been  detected  in  the  body,  namely,  glycuronic  acid.  This 
substance  has  been  obtained  from  the  blood,  liver,  and  urine,  and 
exists  usually  combined  with  various  toxic  or  injurious  substances, 
such  as  the  phenols  or  camphor.  When  these  substances  are 
given  to  animals  or,  as  in  the  case  of  the  phenol,  are  formed  in  the 
body,  they  are  apparently  conjugated  with  glycuronic  acid  and 

*  Dakin  and  Dudley,  "Journal  of  Biological  Chemistry,"  14,  155,  1913. 
f  Lusk,  "The  Science  of  Nutrition/'  3d  ed.,  1917,  p.  260. 


918  NUTRITION    AND    HEAT    REGULATION. 

excreted,  somewhat  as  the  phenol,  indol,  etc.,  are  conjugated 
with  sulphuric  acid  and  excreted.  The  relationship  of  glycuronic 
acid  to  sugar  is  indicated  by  the  following  formulas: 

CH2OH  COOH 

(CHOH)4        (CHOH)4 

COH  COH 

Dextrose.          Glycuronic  acid. 

Whether  this  product  is  used  solely  for  protection  against  toxic 
substances,  or  constitutes  one  member  of  a  normal  series  of  metabo- 
lisms of  the  sugar  molecule  has  not  been  determined. 

Regulation  of  the  Sugar-supply  of  the  Body. — The  regulation 
of  the  sugar-supply  of  the  body  is  a  matter  of  the  greatest  im- 
portance. On  the  one  hand  we  have  the  process  of  the  conversion 
of  sugar  to  glycogen,  glycogenesis,  as  it  has  been  called,  and  the 
subsequent  gradual  reconversion  of  this  glycogen  to  sugar  (glyco- 
genolysis),  according  to  the  needs  of  the  body.  On  the  other  hand, 
we  have  the  processes  of  consumption  of  sugar  in  the  tissues  for 
energy  purposes,  a  process  designated  often  as  glycolysis,  the 
nature  of  which  is  discussed  in  the  preceding  paragraph.  It  is 
evident  that  these  various  processes  must  be  adapted  one  to  an- 
other, for  we  know  that  if  for  any  reason  the  percentage  of  sugar 
in  the  blood  rises  but  slightly  above  the  normal,  a  condition  desig- 
nated as  hyperglycemia,  there  occurs  an  escape  of  sugar  in  the 
urine  (glycosuria) .  Regulations  undoubtedly  exist  for  the  control 
and  adaptation  of  these  several  processes,  and  at  one  point  or 
another  these  regulations  may  break  down  with  a  resulting  dis- 
turbance in  sugar  consumption  that  manifests  itself  usually  by 
the  development  of  a  condition  of  glycosuria.  In  the  first  place 
it  may  be  recalled  that  glycosuria,  so-called  alimentary  glycosuria, 
may  result  from  eating  an  excess  of  carbohydrate.  In  this  case 
apparently  sugar  absorbed  from  the  alimentary  tract  is  sup- 
plied to  the  liver  more  rapidly  than  the  latter  organ  can  synthe- 
size it  to  glycogen.  The  breakdown  in  regulation  is  in  the  proc- 
ess of  glycogenesis.  Stimulation  of  sensory  nerves  or  lesions  of 
the  central  nervous  system  may  also  produce  glycosuria.  One  of 
the  most  interesting  experiments  in  this  connection  is  the  piqiire 
or  "sugar  puncture,"  first  noted  by  Claude  Bernard  (1855).  A 
slight  puncture  of  the  medulla,  made  between  the  levels  of  ori- 
gin of  the  vagus  and  auditory  nerves,  results  in  the  appearance  of 
sugar  in  the  urine.  The  phenomenon  has  been  much  investigated, 
and  opinions  have  differed  as  to  the  mechanism  of  the  reaction. 
According  to  the  older  view,  the  increased  sugar  production  is  due 
to  the  fact  that  the  puncture  stimulates  nerve-fibers  that  act  upon 
the  liver  cells  and  cause  an  augmentation  of  the  process  of  glyco- 
genolysis.  The  nerve-fibers  in  question  pass  down  the  cord  and, 


CARBOHYDRATES  AND  FATS.  919 

entering  the  splanchnic  nerves,  proceed  to  the  liver  by  way  of  the 
hepatic  plexus  and  nerves.  On  this  view  the  center  in  the  medulla 
constitutes  a  "sugar-regulating  center,"  which  may  be  acted  on 
reflexly  and  thus  control  the  process  of  the  conversion  of  glycogen 
to  sugar.  Others  have  held  the  view  that  the  effect  is  exercised 
indirectly  through  the  adrenal  glands.  They  believe  that  the 
sugar  puncture  results  in  a  reflex  stimulation  of  the  adrenal 
glands,  whereby  more  epinephrin  is  thrown  into  the  circulation, 
and  that  the  increase  in  glycpgenolysis  is  due  to  the  action  of  the 
epinephrin  on  the  liver  cells.  Recent  experiments  do  not  support 
wholly  either  one  of  these  views,  but  indicate  rather  that  while  the 
nerve-fibers  involved  act  directly  upon  the  liver  cells  the  presence 
of  the  adrenal  glands  is  in  some  way  necessary  for  the  reaction.* 
Just  how  this  mechanism  acts  under  normal  conditions  cannot, 
therefore,  be  determined.  It  is  known,  however,  that  under  condi- 
tions of  emotional  excitement  or  nervous  stress  glycosuria  is  apt  to 
occur,  and  the  explanation  usually  offered  is  that  the  secretion  of 
the  adrenals  is  increased  by  reflex  stimulation  with  a  resulting  in- 
crease in  sugar  output  from  the  liver.  In  both  of  these  possibilities, 
a  reflex  stimulation  of  the  hepatic  nerves  or  of  the  adrenal  glands, 
there  is  a  break  down  in  the  completeness  of  the  regulation  which 
affects  chiefly  the  process  of  glycogenolysis.  There  is  an  acceler- 
ated conversion  of  glycogen  to  sugar,  or,  as  it  is  sometimes  fig- 
uratively expressed,  a  mobilization  of  the  sugar  reserves.  Within 
certain  limits  this  reaction  may  be  regarded  as  a  provision  or 
adaptation  for  increasing  the  supply  of  energy-yielding  material  to 
the  muscles  under  conditions  which  usually  demand  great  muscular 
activity.  But  when  the  stimulus  is  excessive  the  output  of  sugar 
may  be  sufficiently  great  to  bring  about  an  approach  to  a  patho- 
logical condition  since  it  leads  to  hyperglycemia  and  glycosuria. 
In  this  connection  we  may  recall  also  the  severe  form  of  glycosuria 
following  upon  removal  of  the  pancreas,  the  so-called  pancreatic 
diabetes  (p.  896).  Here  also  the  trouble  is  referable  to  a  change  in 
one  of  the  internal  secretions,  but  in  this  instance  it  is  a  defective 
rather  than  an  excessive  secretion  which  induces  the  glycosuria. 
Whether  the  loss  of  the  internal  secretion  of  the  pancreas  affects 
the  stage  of  glycogenolysis  or  the  stage  of  glycolysis  is  perhaps  an 
open  question.  The  usual  view  has  been  that  this  secretion  is  con- 
cerned somehow  with  the  metabolism  of  sugar  in  the  tissues  in 
some  such  way  as  is  suggested  in  the  preceding  paragraph  upon 
the  intermediary  metabolism  of  the  carbohydrates. 

In  mankind  defective  sugar  metabolism  manifests  itself  chiefly 
in  the  disease  known  as  diabetes  mellitus.    In  this  severe  and  often 

*  For  review  and  literature  consult  Macleod,  Harvey  Lecture,  "Journal  of 
the  American  Medical  Association,"  April  18, 1914. 


920  NUTRITION   AND    HEAT    REGULATION. 

fatal  disease  the  amount  of  sugar  lost  daily  in  the  urine  may  be  very 
large.  In  severe  forms  of  the  disease  practically  all  the  carbohydrate 
of  the  food  may  be  excreted  in  the  urine  in  the  form  of  sugar, 
and  even  when  the  carbohydrate  in  the  diet  is  eliminated  com- 
pletely, sugar  continues  to  be  secreted  in  the  urine  in  consider- 
able amounts.  In  these  latter  cases  the  sugar  is  supposed  usually  to 
have  its  source  in  the  proteins  of  the  food  or  of  the  body,  a  view 
which  is  supported  by  the  fact  that  the  amount  of  nitrogen  and 
dextrose  excreted  in  the  urine  exhibit  a  constant  relation  to  each 
other.  The  ratio  of  dextrose  to  nitrogen  (D  :  N)  in  a  carbohydrate- 
free  diet  is  given  as  3.65  to  1.*  If  the  amount  of  protein  in  the  diet 
is  increased  there  is  an  increased  elimination  of  sugar  as  well  as 
nitrogen  in  the  urine,  the  proportion  of  3.65  grams  of  dextrose  to 
1  gram  of  nitrogen  remaining  practically  unchanged.  The  obvious 
explanation  of  this  constant  relationship  is  that  the  sugar  is  formed 
from  the  protein,  and  it  may  be  estimated  (Lusk)  on  the  basis  of 
the  ratio  3.65  to  1  that  58  per  cent,  of  the  metabolized  protein  is 
converted  to  sugar.  In  pancreatic  diabetes  in  dogs  a  lower  ratio 
of  2.8  to  1  is  reported.  The  general  and  specific  symptoms  ob- 
served in  diabetes  mellitus  closely  resemble  those  observed  upon 
dogs  suffering  from  pancreatic  diabetes.  It  seems  probable,  there- 
fore, that  in  man  the  condition  of  diabetes  may  also  be  due  in  the 
first  place  to  some  trouble  in  the  pancreas  which  prevents  it  from 
giving  off  its  normal  internal  secretion.  Whether  or  not  the  activity 
of  the  pancreas  is  impaired  in  all  these  cases,  the  majority  of  those 
who  have  studied  the  subject  agree  that  the  final  difficulty  lies 
in  the  fact  that  the  tissues,  especially  the  muscular  tissues,  can- 
not utilize  the  sugar  brought  to  them  by  the  blood,  f  Assuming  the 
correctness  of  the  usual  view,  it  has  been  a  question  as  to  what  part 
of  the  process  of  glycolysis  is  affected.  This  process  it  will  be  re- 
membered is  supposed  to  comprise  two  general  stages,  a  series  of 
preparatory  non-oxidative  changes  and  a  terminal  series  of  oxida- 
tions yielding  CO2  and  H2O.  Corresponding  to  this  general  point 
of  view,  some  authors  have  supposed  that  in  the  diabetic  individual 
the  activity  of  the  enzymes  responsible  for  the  preparatory  changes 
is  at  fault,  while  others  have  supported  the  opposite  theory.  At 
present  experiments  on  dogs  exhibiting  pancreatic  diabetes  seem  to 
favor  the  view  that  it  is  the  second  stage  that  is  interfered  with.  | 
In  addition  to  the  sugar  found  in  the  urine  in  diabetes,  this  secre- 
tion may  also  contain  considerable  amounts  of  the  acetone  bodies, 
namely,  /3-oxy butyric  acid,  aceto-acetic  acid,  and  acetone.  It 

*  Lusk,  "Elements  of  the  Science  of  Nutrition,"  Philadelphia,  3d  ed.,  1917. 

fFor  literature  on  the  Metabolism  of  Diabetes,  see  Lusk,  "Archives  of 
Internal  Medicine,"  Feb.,  1909;  Magnus-Levy,  "The  Medical  Record,"  Dec. 
3,  1910,  and  Minkowski,  ibid.,  Feb.  1,  1913. 

t  Verzar,  " Biochemische  Zeitschrift,"  66,  75,  1914. 


CARBOHYDRATES    AND    FATS.  921 

is  probable  that  these  bodies  represent  intermediary  products 
in  the  metabolism  of  the  fats  of  the  body  which  escape  oxidation. 
The  large  accumulation  of  these  acid  bodies  in  the  blood  and  tissues 
of  the  diabetic  is  responsible  for  the  production  of  the  serious  con- 
dition of  acidosis  shown  by  those  suffering  from  severe  forms  of 
this  disease.  There  is  no  wholly  satisfactory  explanation  of  the 
relationship  between  the  loss  of  power  to  metabolize  the  sugar  and 
this  accompanying  incompleteness  in  the  normal  processes  of  oxi- 
dation of  the  fat. 

Phlorhizin  Diabetes. — Phlorhizin  is  a  vegetable  glucoside  ob- 
tained from  the  roots  of  certain  trees — e.  g.,  apple,  pear.  When 
injected  into  an  animal  it  causes  a  glycosuria  which  is  temporary, 
but  which  may  be  renewed  by  repeated  injections.  Examination 
of  the  blood  in  this  case  reveals  the  fact  that  the  percentage  of 
sugar  is  not  increased,  so  that  the  immediate  cause  of  the  glycosuria 
is  different  from  that  responsible  for  the  diabetes  of  man  or  of 
animals  without  the  pancreas.  Sugar  given  to  a  phlorhinized 
animal  is  all  excreted  in  the  urine,  and  the  same  is  true  of  the  sugar 
formed  in  the  body  from  protein,  so  that  the  interference  with  sugar 
metabolism  is  complete  as  long  as  the  action  of  the  drug  continues. 
A  satisfactory  explanation  of  the  action  of  the  phlorhizin  has  not 
yet  been  obtained,  but  it  would  seem  that  the  drug  acts  primarily 
in  some  way  upon  the  kidney  itself.  It  has  been  suggested  (Stiles 
and  Lusk*)  that  the  sugar  exists  in  part  in  the  blood  in  a  colloidal 
combination  and  that  under  the  influence  of  the  phlorhizin  this 
combination  is  broken  up  in  the  kidney  and  the  sugar  is  liberated 
in  a  form  in  which  it  is  easily  excreted.  Experimental  work,  how- 
ever, has  failed  to  confirm  this  hypothesis,  f 

From  this  brief  description  of  the  fate  of  the  carbohydrate 
in  the  body  it  is  evident  that  its  history  as  a  food-stuff  might 
be  considered  conveniently  under  three  heads,  namely,  its  supply, 
its  storage,  and  its  consumption.  The  supply  is  regulated  by  the 
diet.  In  the  usual  diet  carbohydrate  constitutes  the  chief  and 
also  the  most  variable  factor.  Its  cheapness,  its  ease  of  digestion 
and  of  consumption  make  it  the  most  convenient  and  economical 
source  of  energy  to  the  body.  When  our  energy  needs  are  large, 
as  in  muscular  work,  the  carbohydrate  portion  of  the  diet  is 
increased;  when  the  energy  needs  are  small,  as  in  a  sedentary 
life,  the  amount  of  carbohydrate  is  reduced.  The  storage  of 
carbohydrate  in  the  body  is  provided  for  temporarily  by  the 
glycogenetic  function  of  the  liver  and  the  muscles.  This  function 
may  be  deranged  for  a  time  by  injuries  to  the  central  nervous 

*  Stiles  and  Lusk,  "American  Journal  of  Physiology/'  10,  67,  1903. 
f  See  Hess  and  McGuigan,"  Journal  of  Pharmacology  and  Exp.  Thera- 
peutics," 6,  45,  1914. 


922  NUTRITION    AND    HEAT    REGULATION. 

system  or  by  hypersecretion  of  the  adrenal  glands  or  the  hypophy- 
sis, in  which  case  hyperglycemia  and  glycosuria  result.  Or  the 
glycogenetic  tissues  may  be  inadequate  to  handle  all  the  sugar 
absorbed  from  the  alimentary  canal  (alimentary  glycosuria), 
and  in  this  case  also  there  is  a  temporary  hyperglycemia  and 
glycosuria.  At  the  consumption  end  the  amount  of  sugar  de- 
stroyed is  controlled  by  the  energy  needs  of  the  tissues,  especially 
of  the  muscles.  Failure  to  destroy  the  sugar  at  this  point  brings 
on  also  a  hyperglycemia  and  glycosuria  of  a  more  serious  nature. 
Our  sugar-regulating  mechanism  in  fact  may  prove  inadequate 
in  one  of  four  general  ways,  which  may  be  tabulated  briefly  as 
follows : 

1.  Conversion  of  sugar  to  glycogen  (liver)  breaks  down  in 
alimentary  glycosuria. 

2.  Conversion  of  glycogen  to  sugar  (liver)  breaks  down  hi 
injuries  to  the  central  nervous  system,  excessive  internal  secretion 
by  adrenal  gland,  etc. 

3.  Glycolysis  of  sugar  (muscles  and  other  tissues)  breaks  down 
in  diabetes  mellitus  and  pancreatic  diabetes. 

4.  The  normal  impermeability  of  the  kidney  breaks  down  in 
phlorhizin  diabetes. 

Functions  of  the  Carbohydrate  Food. — The  general  value  of 
the  carbohydrate  food  to  the  organism  may  be  summarized  as 
follows:  (1)  It  furnishes  a  source  of  energy  for  the  needs  .of  the 
tissue  cells  and  particularly  for  muscular  work.  It  will  be  remem- 
bered that  the  glycogen  of  a  muscle  disappears  in  proportion 
to  the  work  done  by  the  muscle,  and,  indeed,  prolonged  muscu- 
lar work,  especially  during  starvation,  may  wipe  out  quickly  the 
entire  store  of  glycogen  in  the  body,  in  the  liver  as  well  as  in 
the  muscles.  It  is  usually  believed,  therefore,  that  the  oxida- 
tion of  the  sugar  furnishes  energy  which  by  the  machinery  of 
the  muscles  is  utilized  to  do  work, — that  is,  to  cause  muscular 
contractions.  It  seems  probable  that  under  normal  conditions  this 
material  furnishes  the  main,  if  not  the  sole  source  of  energy  for 
muscular  work.  (2)  The  oxidation  of  the  sugar  furnishes  an  im- 
portant part  of  the  constant  supply  of  heat  needed  by  the  body. 
Each  gram  of  sugar  on  oxidation  yields  —  4  Calories  of  heat,  and, 
since  the  carbohydrates  form  the  largest  part  of  our  diet  and  are 
easily  oxidized  in  the  body,  they  must  be  regarded  as  an  especially 
available  material  for  keeping  up  the  supply  of  animal  heat.  The 
largest  part  of  the  energy  liberated  by  the  oxidation  of  sugar  in  the 
muscles  during  contraction  takes  the  form  of  heat,  and  even  dur- 
ing muscular  rest  the  condition  of  tone  is  probably  attended  by  a 
constant  oxidation  of  this  material.  (3)  The  oxidation  of  the  sugar 
protects  the  protein  of  the  body.  Attention  has  already  been 


CARBOHYDRATES   AND    FATS.  923 

called  to  the  fact  that  an  animal  may  be  kept  in  nitrogen  equilibrium 
on  a  relatively  small  protein  diet  provided  carbohydrates  (or  fats) 
are  also  eaten.  One  may  say,  in  fact,  that  as  the  carbohydrate  food 
is  increased  the  protein  food  may  be  diminished,  down  to  a  certain 
irreducible  minimum  which  is  probably  the  amount  necessary 
for  the  reconstruction  of  new  tissue.  From  the  chemical  com- 
position of  carbohydrates  it  is  evident  that  they  alone  cannot  serve 
to  build  up  protoplasm.  An  animal  fed  on  carbohydrate  food 
alone,  no  matter  how  abundant  the  supply,  would  eventually 
starve  to  death.  Within  certain  limits,  however,  the  carbohy- 
drates are  protein  sparers;  the  energy  provided  by  their  oxidation 
keeps  up  the  supply  of  heat  and  enables  the  muscles  and  the  other 
tissues  to  obtain  the  energy  necessary  for  their  special  kind  of 
work,  and  in  this  way,  chiefly,  the  carbohydrates  protect  the  living 
protein  from  consumption  and  enable  us  to  reduce  the  protein 
material  in  our  diet.  Experiments  show,  in  fact,  that  carbo- 
hydrate is  much  more  efficient  as  a  sparer  of  protein  than  fat. 
An  animal  fed  on  carbohydrates  alone  loses  less  protein  from  the 
body  than  when  kept  on  a  fat  diet  containing  the  same  amount  of 
heat  energy,  and  the  minimal  amount  of  protein  upon  which  the 
body  may  be  kept  in  nitrogen  equilibrium  is  much  lower  when 
the  protein  is  combined  with  an  abundant  supply  of  carbohydrate 
than  in  the  case  of  a  diet  of  protein  and  fat  together.  It  would 
seem  that  the  body  must  always  have  sugar  to  oxidize.  If  this 
material  is  not  furnished  in  the  food,  it  is  obtained  by  breaking 
down  the  body  protein  itself,  as  is  indicated  by  the  continued 
formation  of  sugar  in  diabetes  and  also  by  the  fact  that  even  in 
prolonged  starvation  the  sugar  contents  of  the  blood  are  kept  at 
a  normal  level.  (4)  Any  excess  of  carbohydrate,  taken  as  food, 
beyond  the  power  of  the  tissues  to  store  as  glycogen  may  be 
synthesized  to  form  fat.  Nutritional  experiments,  described 
below,  leave  no  doubt  that  the  fat  of  the  body  may  be  formed 
from  carbohydrate  food.  It  is  stated  that  the  fat  of  the  body 
having  this  origin,  so-called  carbohydrate  fat,  is  of  a  more  solid 
consistency  than  the  fat  derived  from  other  sources.  (5)  To  some 
extent  carbohydrate  may  be  utilized  in  constructive  processes. 
Nucleic  acid  contains  a  carbohydrate  group,  and  we  have  evidence 
from  the  experiments  of  Osborne  and  Mendel  on  growing  rats  that 
the  body  can  make  its  own  nucleic  acid.  A  carbohydrate  group 
forms  part  of  the  molecular  complex  of  some  proteins  and  is  a  con- 
stant constituent  of  the  cerebrosides  found  so  abundantly  in  the 
central  nervous  system.  A  carbohydrate,  lactose,  is  a  normal  con- 
stituent of  the  secretion  of  the  mammary  glands.  In  these  and 
similar  cases  it  is  not  clear  whether  the  carbohydrate  group  is 
derived  from  the  carbohydrate  of  the  food  or  is  constructed  from 


924  NUTRITION    AND    HEAT    REGULATION. 

other  sources,  but  the  former  view  must  be  reckoned  among  the 
possibilities  in  enumerating  the  various  functions  that  may  be  ful- 
filled by  the  carbohydrate  of  the  food. 

Nutritive  Value  of  Fats. — The  fats  of  food  are  absorbed  into 
the  lacteals,  chiefly  as  neutral  fats — the  so-called  chyle  fat.  The 
chyle  fat  is  transported  to  the  blood  by.  way  df  the  great  thoracic 
duct,  and  after  it  is  poured  into  the  blood  it  remains  in  the  cir- 
culation for  a  considerable  time,  being  slowly  picked  out  by  the 
tissues  which  can  use  it  in  their  metabolic  processes.  Within 
these  tissues  it  is  oxidized  to  supply  the  energy  needs  of  the  cells. 
The  final  products  of  the  oxidation  are  the  same  as  when  fat  is 
burnt  outside  the  body — namely,  CO2  and  H2O — and  a  corre- 
sponding amount  of  energy  must  be  liberated.  Speaking  generally, 
then,  the  essential  nutritive  value  of  the  fats  is  that  they  furnish 
energy  to  the  body,  and,  from  a  chemical  standpoint,  they  must 
contain  more  available  energy,  weight  for  weight,  than  the  proteins 
or  the  carbohydrates.  In  a  well-nourished  animal  a  large  amount 
of  fat  is  found  normally  in  the  adipose  tissues,  particularly  in  the 
so-called  "panniculus  adiposus"  beneath  the  skin,  in  the  folds 
of  the  peritoneum,  etc.  Physiologically,  this  body  fat  is  to  be 
regarded  as  a  reserve  supply  of  nourishment.  When  fatty  food 
is  eaten  and  absorbed  in  excess  of  the  actual  metabolic  processes 
of.  the  body,  the  excess  is  stored  in  the  adipose  tissue  as  fat,  to  be 
drawn  upon  in  case  of  need — as,  for  instance,  during  partial  or 
complete  starvation.  A  starving  animal,  after  its  small  supply 
of  glycogen  is  exhausted,  lives  entirely  upon  body  proteins  and 
fats;  the  larger  the  supply  of  fat,  the  more  effectively  will  the 
protein  tissues  be  protected  from  destruction.  In  accordance  with 
this  fact,  it  has  been  shown  that  when  subjected  to  complete 
starvation  a  fat  animal  survives  longer  than  a  lean  one.  Our 
supply  of  fat  is  called  upon  not  only  during  complete  abstention 
from  food,  but  also  whenever  the  diet  is  insufficient  to  cover  the 
oxidations  of  the  body,  as  in  deficient  food,  sickness,  etc. 

The  Intermediary  Metabolism  of  the  Fat. — The  fat  absorbed 
as  food  may  subserve  in  general  several  different  purposes:  (1)  It 
may  be  oxidized  with  the  formation  of  heat  energy.  (2)  It  may 
be  stored  in  the  tissues  as  part  of  the  body  fat.  (3)  It  may  be 
synthesized  with  other  substances  to  form  some  more  complex 
constituent  of  the  body,  such  as  lecithin.  (4)  According  to  some 
authors,  it  may  serve  under  certain  conditions  as  a  source  of  sugar. 
This  latter  suggestion  is  not  supported  by  convincing  experiments. 
The  final  fate  of  the  fat  in  the  body  is,  however,  to  be  oxidized  to 
water  and  carbon  dioxid.  The  nature  of  the  processes  involved 
is  not  understood.  It  is  generally  believed  that  the  first  step 
is  the  splitting  of  the  fat  into  fatty  acid  and  glycerin  under  the 


CABROHYDRATES    AND    FATS.  925 

influence  of  the  lipase  found  in  so  many  of  the  tissues  of  the  body. 
The  fat  that  lies  in  the  storage  tissues — skin,  peritoneum,  etc.— 
does  not  undergo  oxidation  in  these  places.  In  times  of  need  it  is 
absorbed  and  distributed  to  the  more  active  tissues,  and  in  this 
initial  process  of  solution  it  is  probable  that  a  regulative  influence  is 
exerted  by  the  lipase  as  suggested  by  Loevenhart  (see  p.  750); 
that  is,  by  its  reversible  action  this  enzyme  may  control  the  output 
of  fat  to  the  blood,  as  the  supply  of  sugar  in  the  blood  is  kept  con- 
stant by  the  diastatic  enzyme  of  the  liver.  After  the  action  of  the 
lipase  we  can  only  say  that  oxidation  takes  place,  but  through  how 
many  stages  is  not  known.  It  seems  probable  that  the  long  carbon 
chain  of  the  fats  (stearic  acid  =  CH3(CH2)i6COOH)  is  deprived 
in  succession  of  its  carbon  atoms  by  oxidation,  with  the  formation 
of  simpler  fatty  acids,  but  little  positive  evidence  has  been  obtained 
of  intermediate  products.  Perhaps  the  most  significant  fact  known 
bearing  upon  this  point  is  that  under  conditions  which  involve  a 
large  destruction  of  fat  in  the  body,  as  in  starvation,  fevers,  and 
especially  in  diabetes,  /3-oxybutyric  acid  together  with  aceto-acetic 
acid  and  acetone  are  excreted  in  the  urine.  These  three  substances 
are  designated  as  the  acetone  bodies,  and  their  appearance  in  the 
urine  makes  the  condition  known  as  acetonuria.  The  oxybutyric 
acid  is  usually  regarded  as  the  source  of  the  other  two,  as  may  be 
inferred  from  their  formulas.  /3-oxybutyric  acid  =  CH3CHOHCH2- 
COOH.  By  oxidation  this  yields  aceto-acetic  acid,  CHsCOCH^ 
COOH,  and  this  by  loss  of  CO2  is  converted  to  acetone,  CH3- 
COCH3.  Other  observers  incline  to  the  view  that  the  aceto- 
acetic  acid  is  the  primary  product  formed  in  the  metabolism  and 
that  the  oxybutyric  acid  arises  from  it  by  reduction.  The  occur- 
rence of  these  bodies  is  in  accord  with  the  view  of  a  serial  oxidation 
of  the  fatty  acids  furnished  by  the  fats.  Knoop*  has  given  experi- 
mental evidence  for  the  view  that  the  oxidation  takes  place  at  the 
beta-carbon,  and  that  by  a  series  of  such  beta-oxidations  the  long 
carbon  chain  may  be  reduced,  by  the  loss  of  two  carbon  atoms  at  a 
time,  to  simpler  fatty  acids.  Thus,  in  stearic  acid,  Ci5H3iCH2CH2- 
COOH,  oxidation  at  the  beta-carbon  may  be  assumed  to  give  first  a 
beta-ketonic  acid,  Ci5H3iCOCH2COOH,  which,  by  further  oxida- 
tion, loses  two  carbon  atoms,  with  the  production  of  C02  and  H2O, 
and  yields  a  saturated  fatty  acid,  CisHaiCOOH,  of  simpler  struc- 
ture. On  this  theory  if,  as  is  the  case  with  the  fatty  acids  of  animal 
fat,  there  is  an  even  number  of  carbon  atoms  in  the  molecule  to 
start  with,  all  of  the  simpler  acids  formed  by  the  process  of  beta- 
oxidation  will  also  have  an  even  number  of  carbon  atoms.  This  is 
the  case  with  the  butyric  acid  which  so  far  represents  the  concrete 
example  of  these  intermediate  stages,  and  the  same  fact  is  observed 

*  Knoop,  "Hofmeister's  Beitrage,"  6,  150,  1904. 


926  NUTRITION    AND    HEAT    REGULATION. 

for  the  fatty  acids  found  in  milk.  It  is  to  be  borne  in  mind  that 
butyric  acid  and  its  oxyacid  may  be  derived  theoretically,  at  least, 
from  proteins  as  well  as  fats.  As  has  been  shown  in  the  previous 
pages,  the  amino-acids  formed  from  the  proteins  may  suffer  deami- 
nization  in  the  body,  leaving  behind  an  oxy-  or  ketonic  acid  which 
may  then  behave  as  do  the  similar  acids  formed  by  oxidation  of  the 
higher  fatty  acids.  Experiments  have  demonstrated  that  in  this 
way  oxybutyric  acid  may  be  derived  from  a  protein  source. 

Origin  of  the  Body  Fat. — The  views  upon  the  origin  of  body 
fat  have  undergone  a  number  of  changes  in  the  last  fifty  or  sixty 
years,  illustrating  in  an  interesting  way  how  development  of  our 
experimental  methods  leads  often  at  first  to  half-truths  which  are 
corrected  later  by  more  extensive  work.  Dumas  and  others  (1840) 
held  to  the  natural  view  that  the  fat  of  the  body  originates  directly 
from  the  fat  of  the  food.  Liebig,  applying  his  more  exact  methods, 
demonstrated  that  in  some  cases  at  least  this  source  is  insufficient 
to  account  for  all  the  fat.  The  fat  yielded  by  the  milk  of  a  cow 
for  instance,  may  be  greater  in  quantity  than  the  fat  contained 
in  the  food.  He  also  pointed  out  that  the  fat  of  each  species  of 
animal  is  more  or  less  peculiar,  the  fat  of  the  sheep  having  a  higher 
melting  point  than  pork  fat,  and  both  differing  in  composition  from 
the  fat  taken  as  food.  "In  hay  or  the  other  fodder  of  oxen  no 
beef  suet  exists,  and  no  hog's  lard  can  be  found  in  the  potato  refuse 
given  to  swine."  He  was  led  to  attribute  the  source  of  body  fat 
chiefly  to  the  carbohydrate  food,  and  this  belief  agreed  well  with 
the  experience  of  agriculturists  as  to  the  use  of  such  foods  in  fatten- 
ing animals  for  market.  This  view,  in  turn,  was  displaced  by  the 
theory  of  Voit,  supported  by  elaborate  feeding  experiments.  Voit 
believed  that  the  fat  of  the  body  is  formed  mainly  or  entirely  from 
the  protein  of  the  food,  the  carbohydrate  and  the  fat  of  the  diet 
being  useful  only  to  protect  a  part  of  this  protein  from  oxidation. 
Voit's  experiments  have  been  shown  by  Pfliiger  to  have  been  based 
upon  erroneous  analyses  of  the  meat  used  in  his  experiments.  Voit 
assumed  that  in  this  meat  the  ratio  -Q-  is  equal  to  1.34  to  1.37,  while 
Pfliiger  showed  that  it  is  lower,*  1.33.  The  modern  point  of  view 
is  that  the  fat  of  the  body  originates  partly  from  the  fat  of  the  food, 
particularly  in  carnivora,  and  partly  from  the  carbohydrate  of  the 
food,  especially  in  herbivora,  in  whose  diet  this  foodstuff  forms 
such  a  large  part.  The  possibility  that  fat  may  also  be  formed 
from  protein  food  must  be  accepted  in  accordance  with  what  has 
been  stated  above  concerning  the  intermediary  metabolism  of 
the  protein.  So  far  as  the  amino-acids  formed  from  the  food  pro- 
tein during  digestion  are  not  reconstructed  into  the  body-protein 

*Pfluger's"Archiv  f .  die  gesammte  Physiologic,"  51,  229,  1892,  and  77, 
521,  1899. 


CARBOHYDRATES    AND    FATS.  927 

of  the  animal,  they  are  deaminized,  and  the  organic  acid  grouping 
left  may  be  converted  to  sugar  and  glycogen,  hence  probably  also 
to  fat.  Protein  constitutes  relatively  only  a  small  fraction  of 
the  daily  diet,  and  the  modern  point  of  view  is  that  body  fat  is 
formed  in  the  first  instance  from  food  fat  and  food  carbohydrates. 

Origin  of  Body  Fat  from  Food  Fat.— The  first  proofs  that 
the  food  fats  may  be  deposited  as  such  in  the  fat  tissues  of  the 
body  were  obtained  by  feeding  foreign  fats  to  dogs  and  demon- 
strating that  these  fats  can  afterward  be  recognized  in  the 
tissues  of  the  animals.*  Linseed  oil,  rape-seed  oil,  and  mutton-fat 
were  used  in  these  experiments.  Secondly,  it  has  been  made 
probable  by  feeding  experiments  that  the  normal  fat  of  the  food 
undergoes  a  similar  fate.  Thus,  Hofmann  used  a  dog  weighing 
26  kgms.  and  allowed  it  to  starve  until  its  weight  was  reduced  to 
16  kgms.  It  was  then  fed  for  five  days  on  a  little  meat  and  large 
quantities  of  fat.  At  the  end  of  that  time  it  was  killed  and  analyzed. 
The  body  contained  1353  gms.  of  fat,  of  which  only  131  gms.  could 
have  come  from  the  protein  used,  assuming  that  this  material 
can  serve  as  a  fat  former.  Much  of  the  fat  found,  therefore,  was 
probably  derived  from  the  fat  of  the  food. 

Origin  of  Body  Fat  from  Carbohydrates. — That  the  body 
fat  may  have  this  origin  has  been  made  probable  or  certain  by 
feeding  experiments.  Thus,  Rubner  fed  a  dog  (5.89  kgms.)  for 
two  days  on  a  diet  of  sugar,  starch,  and  fat  whose  total  carbon 
content  was  equal  to  176.6  gms.  During  this  period  the  animal 
excreted  87.1  gms.  of  carbon.  There  were  retained  in  the  body, 
therefore,  89.5  gms.  carbon.  The  fat  fed,  4.7  gms.,  contained 
(4.7  X  0.77)  3.6  gms.  C.  The  total  nitrogen  excreted  during  this 
period  was  2.55  gms.,  which  indicated  a  metabolism,  therefore,  of 
16  gms.  (2.55  X  6.25)  of  body  protein.  Making  the  improbable 
assumption  that  all  of  the  carbon  of  this  protein  was  retained  in 
the  body,  this  would  account  for  8.32  gms.  C  (16  X  0.52) ;  so  that 
3.6  -j-  8.32  or  12  gms.  C  might  have  originated  from  sources  other 
than  the  carbohydrate  of  the  food,  leaving,  therefore,  89.5  — 12 
or  77.5  gms.  of  C,  which  could  have  arisen  only  from  the  carbohy- 
drate. This  quantity  of  carbon  could  have  been  retained  only  as 
glycogen  or  fat.  Allowing  for  the  greatest  possible  storage  of 
glycogen,  78  gms.  or  34.6  gms.  C,  there  would  still  remain  42.9  gms. 
of  C,  which  could  have  been  retained  only  as  fat.  Numerous  other 
fattening  experiments  of  different  kinds  have  been  made  in  which 
it  has  been  shown  that  the  fat  laid  on  by  the  animal  could  not  be 
accounted  for  by  the  fat  of  the  food,  nor  by  assuming  with  Voit  that 
it  originated  from  the  protein.  The  combined  testimony  of  these 

*Lebedeff,  "Centralblatt  f.  die  med.  Wiss.,"  1881,  and  Munk,  "Vir- 
chow's  Archiv,"  95,  407,  1884. 


928  NUTRITION    AND    HEAT    REGULATION. 

experiments  have  satisfied  physiologists  that  the  tissues  can  pro- 
duce fat  from  sugar.  The  chemistry  of  the  change  is  not  under- 
stood and  cannot  be  imitated  in  the  laboratory,  but  it  is  evident 
that  in  the  long  run  it  involves  a  series  of  important  reductions, 
since  in  the  end  the  oxygen-rich  sugar  is  transformed  to  an  oxygen- 
poor  fat.  In  the  sugar  the  oxygen  constitutes  53  per  cent,  of  the 
molecule,  while  in  fat  it  forms  only  11.5  per  cent.  The  oxygen  split 
off  in  the  series  of  changes  should  appear  as  H2O  and  C02,  and  in 
accordance  with  this  view  it  is  found  experimentally  that  when 
carbohydrate  is  being  stored  as  fat  there  is  an  increase  in  the  respi- 

CO 
ratory  quotient,  that  is,  in  the  ratio  —  -A 

L>2 

The  Source  of  Body  Fat  in  Ordinary  Diets. — For  the  pur- 
poses of  demonstration  the  experiments  made  to  prove  the  origin 
of  body  fat  from  carbohydrate  or  the  fat  of  food  have  made  use 
of  abnormal  diets  and  conditions.  It  would  be  a  matter  of  practical 
interest  to  ascertain  whether  upon  normal  diets  the  fat  of  the 
body  arises  more  easily  from  the  fat  or  from  the  carbohydrate  of 
the  food.  While  the  question  is  one  to  which  a  positive  answer 
cannot  be  given,  it  seems  to  be  probable  that  the  result  varies  with 
conditions  and  the  nature  of  the  animal.  Experience  seems  to 
show  that  carnivorous  animals  can  be  fattened  more  easily  on  a 
fat  diet,  herbivora  on  a  carbohydrate  diet.  In  animals,  like  our- 
selves, there  is  reason  to  believe  that  the  carbohydrates  are  more 
easily  and  more  quickly  destroyed  in  the  body  than  the  fats,  and 
that,  therefore,  the  latter  may  be  more  readily  deposited  in  the  tis- 
sues, although  an  excess  of  carbohydrate  beyond  the  actual  needs 
of  the  bodv  will  also  be  preserved  in  the  form  of  fat  or  glycogen.* 

The  Cause  of  the  Deposit  of  Body  Fat — Obesity. — From  a 
nutritive  standpoint  fat  constitutes  a  storage  material  which  can 
be  called  upon  as  a  source  of  food-energy  during  starvation  or  when 
the  diet  is  inadequate.  It  is  to  be  assumed,  therefore,  that  body-fat 
is  formed  and  deposited  only  when  food  is  ingested  in  excess  of  the 
actual  expenditure  of  energy  by  the  tissues. 

Our  experience  shows  that  individuals  vary  greatly  in  the 
amount  of  body-fat  formed  under  the  ordinary  conditions  of  living. 
The  question  arises  whether  a  tendency  to  lay  on  fat  is  an  indica- 
tion of  a  marked  excess  in  eating,  or  whether  in  such  cases  the 
metabolizing  capacity  of  the  tissues  is  less  than  usual,  so  that  even 
a  moderate  diet  furnishes  an  excess  of  material  which  the  adipose 
cells  store  as  fat.  It  is  certainly  a  general  belief  that  on  one  and 
the  same  diet  some  individuals  lay  on  fat  and  others  do  not.  Our 
knowledge  is  not  sufficient  to  furnish  wholly  satisfactory  answers 

*  Consult  Rosenfeld,  "Ergebnisse  der  Physiologic,"  vol.  i.,  part  I,  1902. 
Complete  literature. 


CARBOHYDRATES    AND    FATS.  929 

to  these  questions,  but  our  present  position  in  regard  to  them  may 
be  indicated  briefly. 

By  observing  the  general  principle  that  an  excess  of  food  over 
the  energy  needs  will  be  converted  into  body-fat  we  can  change 
at  will  the  amount  of  this  fat  through  alterations  in  the  diet  and 
voluntary  variations  in  the  extent  of  the  energy  expenditure.  Indi- 
viduals whose  daily  occupation  requires  much  muscular  work, 
farmers,  laborers,  etc.,  rarely,  as  Voit  says,  show  any  tendency  to 
adiposity.  Their  energy  requirement  is  higher  than  the  average, 
and  even  an  abundant  diet  furnishes  little  or  no  excess.  In  per- 
sons whose  mode  of  living  is  less  active,  excessive  fat  formation  is 
quite  common.  In  such  persons  the  amount  of  fat  may  be  reduced 
by  cutting  down  the  diet  and  by  increasing  the  body  metabolism 
through  muscular  exercise.  The  usual  procedure  is  to  select  a 
diet  containing  from  one-half  to  three-fifths  of  the  calories 
of  the  usual  diet  and  to  see  that  the  reduction  is  made  chiefly 
in  the  fats  and  carbohydrates  which  are  the  fat-forming  con- 
stituents of  the  food.  On  such  a  regimen  there  is  insufficient 
energy  for  the  body  needs  and  the  storage  fat  is  called  upon  to 
make  up  the  deficiency.  By  consulting  the  tables  giving  the  com- 
position of  the  various  common  foods  it  is  easy  to  construct  such 
dietaries  and  to  vary  them  to  suit  the  taste  of  the  individual  con- 
cerned. On  the  other  hand,  it  is  possible,  by  reversing  this  pro- 
cedure, to  fatten  up  a  thin  person.  Muscular  and  mental  rest 
combined  with  an  abundant  diet  containing  much  fat  and  carbo- 
hydrate in  an  easily  assimilable  form  suffices  to  bring  about  an 
excess  of  food  material  in  the  body  which  the  tissues  change  over 
into  fat. 

These  facts  are  true  in  general  and  can  be  demonstrated  on  man 
and  the  domestic  animals.  We  can  reduce  fat  by  muscular  exer- 
cise and  partial  starvation  and  we  can  increase  body-fat  by  mus- 
cular repose  and  stuffing. 

Nevertheless  it  seems  to  be  true  that  individuals  vary  greatly 
in  the  response  that  they  make  to  such  treatment.  We  must  recog- 
nize that  there  are  other  factors  concerned  about  which  we  know 
very  little.  As  suggested  above,  it  is  possible  that  the  energy  re- 
quirements of  the  body  at  rest  may  vary  so  that  a  diet  which  in 
one  person  would  just  cover  these  requirements  might  in  another 
provide  a  considerable  excess.  And  the  level  of  these  energy  re- 
quirements or  energy  expenditures  may  change,  in  the  same  person, 
under  different  conditions  of  health  or  disease.  Some  experimental 
investigations  have  been  made  upon  this  point.  Calorimetric 
studies  on  thin  and  fat  people  of  the  basal  metabolism,  that  is  to 
say,  the  heat  production  of  the  resting  individual  eighteen  hours 
after  a  meal,  show  that  there  is  substantially  no  difference  between 
59 


930  NUTRITION    AND    HEAT    REGULATION. 

the  two  groups  when  the  figures  are  reckoned  for  a  square  meter 
of  skin  surface.*  There  is  no  constitutional  difference,  so  to  speak, 
in  the  intrinsic  metabolizing  capacity  of  the  active  tissues.  On 
the  contrary,  there  seems  to  be  a  rather  astonishing  uniformity . 

It  is  to  be  borne  in  mind  that  we  know  little  or  nothing  concern- 
ing the  special  physiology  of  the  tissue  most  directly  concerned 
in  the  deposition  of  fat,  namely,  the  fat-cells  themselves.  In  a 
certain  way  the  activity  of  these  cells  is  antagonistic  to  that  of  the 
other  tissues.  In  proportion  as  the  adipose  cells  form  and  store 
fat  out  of  the  material  brought  to  them  by  the  blood  they  deprive 
the  other  tissues  of  a  substance  which  they  might  oxidize.  Energy 
that  otherwise  would  be  liberated  as  heat  is  stored  in  the  form  of 
potential  chemical  energy. 

While  the  resting  basal  metabolism  of  the  fat  and  the  thin 
person  may  be  alike,  it  is  possible  that  a  diet  in  excess  of  this  need 
may  be  handled  differently  in  the  two  cases.  In  one  the  excess  may 
be  all  destroyed  by  the  active  tissues,  while  in  the  other  the  fat  tis- 
sues may  claim  a  share.  Any  small  difference  of  this  kind  in  the 
activity  of  the  adipose  cells  would  have  a  cumulative  effect  which 
would  suffice  to  explain  a  tendency  toward  the  laying  on  of  fat. 
Such  suggestions  as  these,  however,  require  some  experimental 
support  before  they  can  be  considered  seriously. 

32> 121- I9is-  an 


CHAPTER  XLIX. 

NUTRITIVE  VALUE  OF  THE  INORGANIC  SALTS  AND 
THE  ACCESSORY  ARTICLES  OF  DIET. 

The  Inorganic  Salts. — The  body  contains  in  its  tissues  and 
fiquids  a  considerable  amount  of  inorganic  material.  When  any 
organ  is  incinerated  this  material  remains  as  the  ash.  If  we  in- 
clude the  bones,  which  are  rich  in  mineral  matter,  the  average 
amount  of  ash  in  the  body  amounts  to  about  4.3  to  4.4  per  cent, 
of  its  weight.  The  bones,  however,  in  the  adult  contain  most  of 
this  ash  (five-sixths).  In  the  soft  tissues,  like  the  muscle,  the  ash 
constitutes  about  0.6  to  0.8  per  cent,  of  the  moist  weight.  The 
ash  consists  of  chlorids,  phosphates,  sulphates,  carbonates,  fluorids, 
or  silicates  of  potassium,  sodium,  calcium,  magnesium,  and  iron; 
iodin  occurs  also,  especially  in  the  thyroid  tissues.  In  the  liquids 
of  the  body  the  main  salts  are  sodium  chlorid,  sodium  carbonate, 
sodium  phosphate,  potassium  and  calcium  chlorid  or  phosphate. 
In  considering  the  organic  foodstuffs  weight  was  laid  upon  their 
value  as  sources  of  energy,  as  well  as  upon  their  function  in  con- 
structing tissue.  The  salts  have  no  importance  from  the  former 
standpoint.  Whatever  chemical  changes  they  undergo  are  not 
attended  by  any  liberation  of  heat  energy — none  at  least  of  suffi- 
cient importance  to  be  considered.  They  have,  however,  most 
important  functions.  They  maintain  a  normal  composition  and 
osmotic  pressure  in  the  liquids  and  tissues  of  the  body,  and  by 
virtue  of  their  osmotic  pressure  they  play  an  important  part  hi 
controlling  the  flow  of  water  to  and  from  the  tissues.  Moreover, 
these  salts  constitute  an  essential  part  of  the  composition  of  living 
matter.  In  some  way  they  are  bound  up  in  the  structure  of  the 
living  molecule  and  are  necessary  to  its  normal  reactions  or  irrita- 
bility. Even  the  proteins  of  the  body  liquids  contain  definite 
amounts  of  ash,  and  if  this  ash  is  removed  their  properties  are 
seriously  altered,  as  is  shown  by  the  fact  that  ash-free  native  pro- 
teins lose  their  property  of  coagulation  by  heat.  The  globulins 
are  precipitated  from  their  solutions  when  the  salts  are  removed. 
The  special  importance  of  the  calcium  salts  in  the  coagulation  of 
blood  and  the  curdling  of  milk  has  been  referred  to,  as  also  the 
peculiar  part  played  by  the  calcium,  potassium,  and  sodium  salts 
in  the  rhythmical  contractions  of  heart  muscle,  the  irritability 
of  muscular  and  nervous  tissues,  and  the  permeability  of  the 
capillary  walls  and  other  membranes.  The  special  importance  of 

931 


932  NUTRITION    AND    HEAT    REGULATION. 

the  iron  salts  for  the  production  of  hemoglobin  is  also  evident  with- 
out comment.  There  can  be  no  doubt,  in  fact,  that  each  one  of  the 
salts  of  the  body  has  a  special  nutritive  value  and  a  special  met- 
abolic history.  The  time  will  doubtless  come  when  the  special 
importance  of  the  potassium,  sodium,  calcium,  and  magnesium  will 
be  understood  as  well,  at  least,  as  we  now  understand  the  signifi- 
cance of  iron,  and  quite  possibly  this  knowledge  will  find  a  direct 
therapeutic  application,  as  in  the  case  of  iron.* 

Fatal  Effects  of  Ash-free  or  Ash-poor  Diets. — Dogs  have 
been  fed  (Forster)  upon  a  diet  composed  of  ash-free  fats  and  carbo- 
hydrates, and  meats  which  had  been  extracted  with  water  until 
the  salts  had  been  much  reduced.  The  animals  were  in  a  moribund 
condition  at  the  end  of  26  to  36  days.  It  is  probable  that  they 
would  have  lived  longer  if  deprived  of  food  entirely,  with  the  excep- 
tion of  water,  since  the  metabolism  of  the  abundant  diet  provided 
helped  to  increase  the  loss  of  salts  from  the  body.  So  also  in  the 
numerous  experiments  made  upon  growing  rats  fed  upon  artificial 
diets,  f  it  has  been  shown  that  if  the  necessary  proteins,  fats,  and 
carbohydrates  are  supplied  but  the  inorganic  salts  are  omitted 
or  furnished  in  improper  proportions  the  animal  promptly  loses 
weight  and  dies.  Recent  dietary  studies,  in  fact,  have  shown  that  in 
selecting  a  well-balanced  diet  attention  must  be  paid  to  the  compo- 
sition in  inorganic  constituents,  as  well  as  to  the  proportions  of 
protein,  fats,  and  carbohydrates.  In  vegetable  foods,  for  example, 
the  ash  of  the  leaves  is  quite  different  from  that  of  the  seed,  and  an 
exclusive  use  of  either  portion  of  the  plant  might  result  in  a  dietary 
insufficiency,  owing  to  the  poorly  balanced  inorganic  ration. 

The  Special  Importance  of  Sodium  Chlorid,  Calcium,  and 
Iron  Salts. — Sodium  chlorid  occupies  a  peculiar  position  among 
the  inorganic  constituents  of  our  diet,  in  that  it  is  the  only  one 
which  we  deliberately  add  to  our  food.  The  other  inorganic 
material  is  taken  unconsciously  in  our  diet,  but  although  sodium 
chlorid  exists  also  in  our  food  in  relatively  large  quantities  we 
purposely  add  more.  It  is  estimated  that  the  average  man  in- 
gests from  10  to  20  gms.  a  day.  This  amount  seems  to  be  in  excess 
of  the  actual  necessities  of  the  body,  since  on  experimental  diets 
individuals  have  been  kept  in  good  condition  when  the  total 
content  in  sodium  chlorid  was  reduced  to  one  or  two  grams. 
This  desire  for  salt  is  exhibited  also  by  many  animals.  The 
farmer  provides  salt  for  his  stock  and  wild  animals  visit  the  salt- 
licks at  intervals.  Bunge  has  called  attention  to  the  fact  that 

*  For  a  brief  summary  of  facts  and  speculations,  see  Alba  and  Neuberg, 
"Physiologic  u.  Pathologic  des  Mineral-Stoffwechsels,"  1906,  and  von  Wendt, 
"Handbuch  d.  Biochemie,"  4,  561,  1911. 

t  Osborne  and  Mendel,  "Journal  of  Biological  Chemistry,"  13,  233,  1912, 
and  McCollum,  "Journal  of  the  American  Medical  Association,"  May  12, 1917. 


INORGANIC    SALTS,    STIMULANTS,    AND    CONDIMENTS.          933 

among  men  and  animals  the  desire  for  salt  is  limited,  for  the  most 
part  at  least,  to  those  that  use  vegetable  food.  From  the  accounts 
of  travelers  he  shows  that  when  a  purely  animal  diet  is  used  there 
is  no  desire  for  salt;  but  on  a  vegetable  diet  there  is  a  craving  for 
it  which  may  become  very  intense  and  unpleasant  when  circum- 
stances prevent  its  being  obtained.  He  offers  an  ingenious 
explanation  for  this  relation.  Most  vegetables  contain  a  large 
amount  of  potassium  salts,  and  in  the  blood  these  salts  react  with 
the  sodium  chlorid.  Thus,  if  .potassium  sulphate  were  added  to 
the  blood  it  would  react  with  sodium  chlorid,  giving  some  potas- 
sium chlorid  and  some  sodium  sulphate.  Both  of  these  salts 
will  be  removed  by  the  kidneys,  since,  except  in  minute  amounts, 
they  are,  so  to  speak,  foreign  to  the  blood.  This  latter  liquid 
will  thereby  lose  some  of  its  supply  of  sodium  salt,  whence  the 
craving  for  more  in  the  food.*  The  content  of  the  blood  in  sodium 
chlorid  remains  remarkably  constant.  When  an  excess  is  taken  in 
the  food  it  is  removed  by  the  kidneys.  On  a  salt-free  diet  or 
in  starvation  the  amount  of  sodium  chlorid  secreted  in  the  urine 
soon  falls  to  a  low  figure  (0.6  gm.),  showing  that  the  tissues  are 
holding  on  to  this  constituent.  It  cannot  be  doubted,  however, 
that  under  ordinary  conditions  we  use  salt  in  quantities  much  larger 
than  is  necessary  to  maintain  the  sodium  chlorid  content  of  the 
blood.  It  is  employed  as  a  condiment  for  its  pleasant  flavor,  and  it 
is  possible  that  its  use  is  often  carried  to  excess.  It  can  be  shown, 
in  fact,  that  by  increasing  the  intake  of  salt  an  edematous  condition 
of  the  tissues  may  be  produced,  owing  to  the  fact  that  the  salt 
increases  the  osmotic  pressure  in  the  tissues.  So  also  in  conditions 
of  edema  or  inflammation  restriction  of  the  salt  of  the  diet  may  give 
the  contrary  result  and  help  to  restore  the  tissues  to  a  normal  state 
as  regards  their  water  contents. 

The  calcium  salts  of  the  body  play  a  most  important  role  in 
connection  with  the  irritability  of  muscle  and  nerve  (p.  576). 
They  are  also  of  obvious  importance  in  furnishing  material  for 
the  growth  of  the  skeleton.  Their  importance  in  this  regard  has 
been  demonstrated  by  feeding  experiments.  Young  dogs  when 
given  a  diet  poor  in  calcium  salts  fall  into  a  condition  resembling 
rickets  in  children,  owing  to  a  deficient  growth  of  the  bones.  Pig- 
eons also,  when  fed  upon  a  similar  diet,  exhibit  an  atrophy  and 
fragility  of  the  bones  due  doubtless  to  the  lack  of  calcium  salts. 
As  in  the  case  of  the  other  food  materials,  there  must  be  a  definite 
calcium  metabolism  in  the  body.  It  is  probable,  indeed  certain,, 
that  most  of  the  calcium  salts  ingested  simply  pass  through  the 
body  without  entering  into  its  structure.  They  are  eliminated 

*  For  an  interesting  discussion,  see  Bunge,  "Physiologic  des  Menschen  " 
vol.  ii.,  p.  103,  1901. 


934  NUTRITION    AND    HEAT    REGULATION. 

unchanged  or  unused  in  the  feces  or  urine.  A  small  portion,  how- 
ever, must  be  absorbed  and  used  and  a  corresponding  amount  must 
be  eliminated  as  a  true  waste  product  of  tissue  metabolism.  Voit, 
by  experiments  upon  isolated  loops  of  the  intestine,  has  shown 
that  some  calcium  is  constantly  eliminated  from  the  inner  surface 
of  the  intestine.  The  amount  is  small,  not  exceeding  perhaps  0.15 
to  0.16  grams  per  day.  There  is  some  evidence  that  the  amount 
of  calcium  in  the  tissues  increases  with  age.  This  is  certainly 
true  of  the  bones,  which  become  exceedingly  brittle  in  advanced 
life,  and  is  evident  also  in  the  arteries,  whose  elasticity  diminishes 
as  the  calcium  salts  deposited  in  their  coats  are  increased.  Under 
pathological  conditions  deposition  of  calcium  salts  (calcium  car- 
bonate) in  the  tissues  may  be  markedly  increased,  as  is  shown 
by  the  condition  of  the  arteries  in  arterial  sclerosis  and  the  con- 
dition of  the  crystalline  lens  in  senile  cataract. 

The  iron  salts  that  are  constantly  necessary  for  the  production 
of  new  hemoglobin  are  provided  in  our  food,  in  which  they  exist 
in  organic  combination.  The  value  of  the  food  in  this  respect 
varies  greatly,  as  may  be  seen  from  the  following  table  selected 
from  Bunge's  analysis: 

100  grns.  of  dry  substance  contain  iron  in  milligrams,  as  follows  : 

White  of  egg trace      Apples 13 

Rice 1  to  2  Cabbage  (green  leaves) ...       17 

Wheat  flour  (bolted) . .     1.6      Beef 17 

Cows'  milk 2.3       Asparagus 20 

Potatoes 6.4      Yolk  of  egg 10  to  24 

Peas 6.2  to  6.6       Spinach 33  to  39 

Carrots 8.6 

In  conditions  of  malnutrition,  particularly  in  the  simple  anemias, 
it  becomes  necessary  to  select  a  diet  with  reference  to  its  contents 
in  iron  or  to  add  iron  deliberately  to  the  diet.  Therapeutically 
iron  may  be  given  in  the  form  of  simple  salts  with  organic  or  mineral 
acids  or  in  more  complex  organic  combination.  There  has  been 
much  controversy  as  to  whether  the  body  is  capable  of  taking 
the  iron  in  inorganic  form  and  synthesizing  it  into  a  molecule  so 
complex  as  that  of  hemoglobin.  Experience,  however,  seem  to 
show  that  this  is  possible,  although  under  normal  conditions  at 
least  our  iron  is  used  in  organic  form.  Bunge  first  isolated  such  a 
compound,  a  nucleo-albumin  containing  iron,  which  he  prepared 
from  the  egg  yolk  and  called  hematogen.  This  compound  must 
serve  as  the  source  of  the  hemoglobin  in  the  developing  chick. 
When  the  diet  is  directed  especially  toward  increasing  the  iron 
food  it  would  seem  to  be  wiser  to  choose  these  compounds,  or,  better 
still,  the  iron-rich  foods,  rather  than  medicinal  preparations  of 
the  inorganic  salts.  The  daily  excretion  of  iron  from  the  body 
takes  place  in  the  feces  rather  than  in  the  urine.  The  experiments 


INORGANIC    SALTS,    STIMULANTS,    AND    CONDIMENTS.          935 

of  Voit  upon  isolated  loops  of  the  intestines,  referred  to  above,  show- 
that  iron  is  eliminated  from  the  walls  of  the  intestine.  The  whole 
history  of  the  metabolism  of  iron  in  the  body  is  surrounded  by 
much  uncertainty.  After  absorption  its  synthesis  to  hemoglobin 
takes  place,  as  to  its  final  stages,  in  the  red  marrow,  but  it  is  possible 
that  other  organs  may  take  part  in  the  formation  of  intermediate 
products.  As  regards  its  elimination,  we  know  that  the  breaking 
down  of  the  hemoglobin  (formation  of  bile  pigments)  occurs  prob- 
ably in  the  liver,  but  the  final  excretion  of  the  iron  takes  place 
mainly  through  the  walls  of  the  intestine. 

Accessory  Articles  of  Diet. — Under  this  general  term  we  may 
include  all  those  bodies  classed  as  condiments,  flavors,  and  stimu- 
lants, which  we  habitually  take  in  our  diet  hi  order  to  enhance  the 
attractiveness  of  the  food.  These  substances  may  or  may  not 
have  some  heat  value  to  the  body — that  is,  they  may  undergo 
oxidation  with  the  liberation  of  heat  energy;  but,  in  general,  their 
value  in  nutrition  is  due  to  other  properties. 

The  Flavors  and  Condiments. — Perhaps  the  most  important 
influence  exerted  by  these  bodies  is  that  by  making  the  food  appe- 
tizing they  increase  the  secretion  of  gastric  juice.  The  origin  of 
the  so-called  psychical  secretion  has  been  described  (p.  781),  and 
there  can  be  little  doubt  that  the  palatableness  of  food  influences 
greatly  the  facility  with  which  its  gastric  digestion  is  accomplished. 
It  is  said,  in  fact,  that  dogs  will  refuse  to  eat  food  that  has  been 
deprived  entirely  of  its  sapidity  and  flavor,  preferring  rather  to 
starve.  Some  of  these  substances  (pepper),  as  also  the  stimulants 
(alcohol),  may  have  an  additional  value  in  that  they  increase  the 
rapidity  of  absorption  from  the  stomach.  Gautier  divides  the 
condiments  into  the  following  classes:  (1)  Aromatics,  comprising 
vanilla,  anise,  cinnamon,  nutmeg,  and  other  similar  essential  oils. 
(2)  Peppers.  (3)  The  alliaceous  condiments, — garlic,  mustard, 
etc.  (4)  The  add  condiments, — vinegar,  citron,  pickles,  etc.  (5) 
The  salty  condiments,  such  as  table  salt.  (6)  The  sugar  condiments. 

The  Stimulants. — Under  this  head  we  include  alcohol,  tea,  coffee, 
chocolate,  or  cocoa,  and  meat  extracts  (beef  tea,  etc.).  Regarding 
the  last  mentioned  substance,  its  physiological  vakie  has  been  made 
clear  by  the  work  of  Pawlow  (p.  781).  Meat  extracts  of  various 
kinds  contain  secretogogues  which  stimulate  the  gastric  glands  to 
secretion.  In  themselves  they  may  contain  very  little  actual 
foodstuff.  Liebig's  extract  contains  some  protein,  gelatin,  and  gly- 
cogen,  which  form  an  actual  nourishment,  but  its  specific  value 
as  a  gastric  stimulant  depends  upon  other  constituents,  possibly  the 
nitrogenous  extractives, — creatin,  xanthin,  carnin,  etc.  Coffee 
and  tea  owe  their  well-known  stimulating  action  to  the  presence 
of  an  alkaloid,  caffein  or  trimethyl-xanthin.  It  may  be  considered 


936  NUTRITION    AND    HEAT    REGULATION. 

.as  xanthin  in  which  three  of  the  hydrogen  atoms  have  been  re- 
placed by  methyl  (CH3)  groups,  as  is  indicated  in  the  following 
structural  formulas: 

HN— CO  CH3N— CO 

CO    C— NH  CO    C— N<CHs 

I       II       ^CH 
CH3N— C— N 

Xanthin.  Caffein. 

This  alkaloid  has  a  diuretic  action  on  the  kidneys  and  a  stimulating 
effect  on  the  nerve  centers,  as  is  illustrated  by  its  effect  in  raising 
blood-pressure  by  an  action  on  the  vasoconstrictor  center.  The 
influence  of  tea  and  coffee  in  preventing  sleepiness  may  be  referred 
to  this  action  on  blood-pressure.  The  use  of  these  substances, 
according  to  general  experience,  augments  muscular  energy  and 
diminishes  the  sense  of  fatigue.  Cocoa,  or  the  chocolate  made 
from  it  by  the  addition  of  sugar,  contains  considerable  nourish- 
ment in  the  form  of  fats,  carbohydrates,  and  proteins,  but  its  stimu- 
lating effect  is  referred  to  the  alkaloid  theobromin  or  dimethyl- 
xanthin,  and  to  some  extent  possibly  to  the  essential  oils  developed 
in  roasting.  The  theobromin  exerts  stimulating  effects  similar  to 
those  of  the  caffein,  and  experiments  indicate  that  in  moderate 
doses  of  from  20  to  30  grams  per  day  cocoa  has  no  perceptible 
injurious  effect.  The  methylxanthins  are  in  part  oxidized  in 
the  body  and  in  part  (one-third)  excreted  in  the  urine. 

Alcohol. — The  physiological  effects  of  alcohol  are  of  peculiar 
interest  to  mankind,  owing  to  its  widespread  use,  and  especially 
to  the  disastrous  results  following  its  intemperate  consumption. 
Those  who  employ  it  in  excess  are  in  danger  of  acquiring  an  alco- 
holic thirst  or  habit  toward  which  the  body  possesses  no  counter- 
acting regulation.  When  food  is  eaten  in  excess  we  experience  a 
feeling  of  satiety  which  destroys  the  desire  for  more  food,  and  the 
same  regulation  prevails  in  the  case  of  water.  With  alcoholic 
drinks,  however,  the  desire  may  continue  long  after  the  alcohol 
taken  has  begun  to  exert  an  injurious  action  upon  the  tissues 
The  evil  effects  of  excessive  use  of  alcohol  are  so  continually  demon- 
strated upon  man  that  there  is  no  need  for  experimental  investi- 
gations to  establish  this  fact.  Pathological  examination  of  the 
tissues  in  the  case  of  confirmed  drunkards  has  demonstrated  the 
existence  of  definite  lesions  in  many  of  the  organs, — stomach, 
liver,  heart,  nervous  system, — and  have  shown  that  under  these 
conditions  it  acts  as  a  tissue  poison.*  This  result  is  exhibited 
not  only  in  cases  of  chronic  alcoholism  in  which  these  lesions 
have  developed  gradually,  but  also  in  cases  of  acute  alcoholism 

*  See  Welch,  "The  Pathological  Effects  of  Alcohol,"  in  "Physiological 
Aspects  of  the  Liquor  Problem,"  vol.  ii.,  1903. 


INORGANIC    SALTS,    STIMULANTS,    AND    CONDIMENTS.          937 

resulting  from  excessive  doses.  On  the  other  hand,  it  is  known 
that  many  individuals  use  alcohol  in  moderate  doses  throughout 
life  with  no  noticeable  evil  result,  but,  on  the  contrary,  with  possible 
benefit,  particularly  in  advanced  life.  The  matter  of  practical 
importance  and  interest  is  to  determine  the  physiological  role  of 
moderate  doses  of  alcohol.  Does  it  serve  a  useful  purpose,  acting 
as  a  food  or  stimulant,  or  is  it  a  poison  in  all  doses  to  a  greater  or 
less  extent  ?  The  literature  upon  the  subject  is  very  large  and 
in  many  respects  conflicting.  Only  a  brief  summary  can  be 
attempted  here.  Regarding  its  stimulating  action  the  general 
experience  of  mankind  attributes  a  result  of  this  kind  to  its  use 
in  small  quantities,  but  the  experimental  evidence  is  of  an  uncer- 
tain nature.  Some  observers  have  claimed  that  the  reaction 
time  is  diminished  after  the  use  of  alcohol,  but  most  of  the  recent 
investigation  goes  to  show  that  in  the  work  of  skilled  labor,  in 
which  the  neuromuscular  machinery  is  involved,  alcohol  even 
in  small  quantities  decreases  the  efficiency.*  It  has  been  sug- 
gested, therefore,  that  as  regards  the  higher  nerve  centers  it  acts 
from  the  beginning  as  a  narcotic  or  paralysant  to  the  inhibitory 
centers.  By  thus  removing  inhibitory  control  there  is  an  apparent 
increase  in  activity  which  is  not  due  to  a  direct  stimulating  effect. 
In  the  comprehensive  experiments  reported  by  Dodge  and  Benedict 
it  is  stated  in  accordance  with  the  above  conclusion  that  alcohol  in 
small  doses,  30  to  45  c.c.,  caused  no  marked  facilitation,  but,  on  the 
contrary,  a  lengthening  or  retardation  of  simple  and  complex  re- 
flexes involving  neuromuscular  mechanisms,  and  a  raising  of  the 
sensory  threshold.  But  in  this  series  of  experiments  also  there  are 
some  contradictions,  since  a  later  report  (Miles)  of  observations 
made  upon  the  same  subject  and  by  the  same  method  states  that 
if  the  period  of  observation  was  extended  over  a  longer  time  the 
results  might  be  reversed,  that  is  to  say,  the  alcohol  might  cause  a 
superior  neuromuscular  activity.  In  the  higher  neural  reactions 
such  as  are  brought  into  play  by  memory  tests  alcohol  caused  an 
improvement  even  in  the  period  (two  hours)  immediately  following 
its  use.  In  view  of  these  varying  results  it  would  seem  to  be  im- 
possible to  make  any  satisfactory  general  statement  in  regard  to  the 
effect  of  small  doses  of  alcohol  upon  the  activities  of  the  nervous 
system.  On  other  mechanisms  indecisive  results  are  reported.  It 
is  stated  that  the  secretion  of  the  gastric  and  of  the  pancreatic  juice 
is  markedly  increased  by  the  use  of  alcohol  in  small  doses,  so  far, 
at  least,  as  the  water  secretion  is  concerned.  The  content  of  the 

*  For  literature  and  discussion,  see  Abel,  "The  Pharmacological  Action  of 
Alcohol,"  in  "Physiological  Aspects  of  the  Liquor  Problem,"  vol.  ii.,  1903; 
and  Horsley  and  Sturge,  "Alcohol  and  the  Human  Body,"  1907;  Dodge  and 
Benedict,  "Carnegie  Institute  Publications,"  No.  232,  1915;  Benedict, 
"Science,"  June  30,  1916. 


938  NUTRITION    AND    HEAT    REGULATION. 

secretion  in  digestive  ferments  seems  to  be  diminished.  On  the 
heart  and  blood-vessels  alcohol  in  small  quantities  appears  to  have 
no  positive  effect  of  a  stimulating  character.  The  pulse  rate  is 
increased,  but  this  is  due  probably  to  a  depressing  effect  on  vagus 
tone.  It  is  known  that  even  in  small  doses  it  causes  a  dilatation 
of  the  skin  vessels,  giving  a  feeling  of  warmth  and  leading  to  in- 
creased loss  of  heat;  but  whether  this  effect  is  due  to  a  stimulation 
of  the  vasodilator  centers  or,  as  seems  more  probable,  to  a  narcotic 
or  depressing  action  upon  the  vasoconstrictor  centers  has  not  been 
definitely  demonstrated.  On  the  respiratory  center,  as  studied 
in  the  isolated  medulla,  alcohol  seems  to  exert  a  genuine  stimulat- 
ing action  (Hooker) .  The  experience  of  explorers  bears  out  the  gen- 
eral view  that  under  conditions  of  stress  and  of  maintained  exertion 
alcohol  is  of  little  value  as  a  stimulant  to  the  neuromuscular  appara- 
tus. Whatever  action  it  has  in  this  direction  is  temporary,  and  is 
due  probably  to  an  initial  stimulating  effect  upon  the  afferent  fibers 
of  the  mucous  membrane  of  the  stomach.  A  drink  of  whisky,  for 
example,  may  remove  promptly  the  feeling  of  faintness  due  to  a 
vasomotor  collapse,  following  an  accident,  by  a  reflex  effect  of  this 
kind  on  the  vasomotor  apparatus.  After  the  day's  work  is  done, 
or  in  conditions  of  mental  depression,  the  use  of  alcohol  may 
remove  the  sense  of  fatigue  and  exhaustion  and  lead  to  a  sense 
of  well-being.  The  most  important  work  of  recent  years  has 
been  directed  toward  determining  the  nutritive  value  of  alcohol. 
Does  it  function  under  any  circumstances  as  a  food?  Much 
depends  in  such  a  discussion  upon  the  meaning  of  the  terms  used. 
In  the  present  brief  statement  it  is  to  be  understood  that  by  food 
is  meant  material  which  can  be  oxidized  in  the  body  with' the 
production  of  usable  energy,  but  without  injurious  effect  upon  the 
tissues,  and  moreover  a  material  whose  consumption  protects 
some  of  the  other  foodstuffs — fats,  carbohydrates,  and  protein 
— from  destruction.  In  the  first  place,  there  is  no  doubt  that  al- 
cohol is  oxidized  in  the  body.  Various  observers  estimate  that  as 
much  as  90  to  98  per  cent,  of  the  alcohol  absorbed  is  destroyed,*  and 
a  study  of  the  respiratory  quotient  (Higgins)  indicates  that  the 
oxidation  of  the  alcohol  begins  very  promptly,  within  five  to  ten 
minutes  after  it  is  taken.  Since  1  gm.  of  alcohol,  when  burnt,  yields 
7  calories  of  heat,  it  is  evident  that  its  oxidation  in  the  body  must 
yield  a  large  supply  of  heat  energy.  The  question  arises  whether 
this  oxidation  of  the  alcohol  occurs  in  addition  to  the  normal  metab- 
olism of  the  protein  and  non-protein  foodstuffs,  or  whether  it  pro- 
tects and  takes  the  place  of  these  foodstuffs.  With  regard  to  the 
non-proteins  a  number  of  observers  have  attempted  to  determine 

*  See  Atwater  and  Benedict,  Bulletin  69,  United  States  Department  of 
Agriculture,  1889;  also  Memoirs  of  the  National  Academy  of  Sciences,  8, 1902. 


INORGANIC    SALTS,    STIMULANTS,    AND    CONDIMENTS.          939 

the  point  by  ascertaining  the  total  carbon  excretion  during  an 
alcohol  period.  If  the  usual  amount  of  material  is  burnt,  and  the 
alcohol  in  addition,  it  is  evident  that  the  carbon  excretion  should  be 
markedly  increased.  Most  observers,  however,  find  that  it  re- 
mains practically  the  same.  Such  results  as  the  following  have 
been  obtained: 

Atwater  and  Benedict  /  Alcohol-free  days. .   251.9  gms.  carbon. 
rt  \  Alcohol  days 238.5     " 

—  13.4     "          " 

T*'-_                               /Alcohol-free  days.  .212.58  gms.  carbon. 
Jijerie \Alcoholdays 220.84     " 

+  8.26     " 

r.i                                    /  Alcohol-free  days.  .214.83  gins,  carbon. 
Uopatt \Alcoholdays 220.87     " 

+  6.04     "          " 

These  results  indicate  that  the  alcohol  is  used  by  the  body  in  place 
of  the  other  carbon-containing  foodstuffs,  and  this  conclusion  is 
corroborated  by  experiments  reported  by  Atwater  and  Benedict 
in  which  the  total  energy  given  off  from  the  body  as  heat  was 
measured  in  a  respiration  calorimeter.  The  average  of  their  ex- 
periments gave  for  the  alcohol  days  2752  calories  and  for  the  alco- 
hol-free days  2723  calories. 

Theoretically  if  the  alcohol  takes  the  place  of  the  other  material  the 
amount  of  carbon  dioxid  excreted  should  be  diminished.  One  gram  of 
alcohol  when  oxidized  furnishes  as  much  heat  as  1.7  gms.  of  sugar  or  0.75  gm. 
of  fat.  But  1  gm.  of  alcohol  when  burnt  yields  only  1.91  gms.  of  CO2,  while 
1.7  gms.  of  sugar  yield  2.77  gms.  CO2,  and  0.75  gm.  of  fat,  2.13  gms.  of  CO2. 
If  fat  were  replaced  by  the  alcohol  the  amount  of  COj  should  be  reduced 
about  10  per  cent.,  while  if  the  sugar  were  replaced  the  reduction  should 
amount  to  31  per  cent.  That  such  a  reduction  is  not  actually  observed  is 
explained  by  the  fact  that  the  alcohol  leads  to  more  muscular  activity  arid 
a  greater  loss  of  heat  from  the  congested  skin,  thus  indirectly  augmenting 
the  oxidations  of  the  body. 

To  determine  whether  the  combustion  of  the  alcohol  protects  the 
protein  material  from  metabolism  to  the  same  extent  as  is  done  by 
carbohydrates  and  fats,  experiments  have  been  made  in  which  the 
individual  was  brought  into  nitrogen  equilibrium  on  a  mixed  diet. 
Then  for  a  given  period  a  portion  of  the  carbohydrate  was  omitted 
and  alcohol  in  isodynamic  amounts  was  substituted.  The  result 
was  an  increase  hi  the  nitrogen  excretion,  showing  that  the  alcohol 
did  not  protect  fully  the  protein  tissue.  In  a  third  period  the 
first  diet  was  resumed,  and  after  nitrogen  equilibrium  had  again 
been  established  the  same  proportion  of  carbohydrate  was  omitted 
from  the  diet,  but  this  time  alcohol  was  not  substituted.  If  the 
diet  was  poor  in  protein  it  was  found  that  less  protein  was  lost  from 
the  body  when  the  alcohol  was  omitted  than  when  it  was  used. 
Hence  alcohol  not  only  did  not  take  the  place  of  the  carbohydrate 
in  protecting  the  protein,  but  it  actually  caused  an  increased  pro- 


940  NUTRITION    AND    HEAT    REGULATION. 

tein  consumption.*  Other  observers  (Neumann,  Rosemann  f)  have 
found  that,  although  the  effect  just  described  may  occur  in  the  first 
few  days,  yet  if  the  alcohol  diet  is  maintained  the  injurious  effect 
exercised  by  it  disappears,  the  body  ceases  to  lose  its  protein  tissue, 
and  may  even  lay  on  protein.  These  results,  taken  with  those 
given  above,  indicate,  therefore,  that  the  alcohol  may  actually 
take  the  place  physiologically  of  fat  or  carbohydrates  as  a  source 
of  energy  and  as  a  protector  of  protein  metabolism.  J  Under  these 
circumstances,  therefore,  it  acts  as  a  true  foodstuff.  It  is  perhaps 
scarcely  necessary  to  emphasize  the  fact  that  this  scientific  con- 
clusion does  not  mean  that  alcohol  can  be  regarded  as  a  prac- 
tical food.  Its  expensiveness,  its  dangers  when  the  dose  is  too 
large,  etc.,  prevent  us  from  regarding  it  in  this  light.  As  Rosemann 
says,  however,  it  is  possible  that  on  account  of  its  ready  absorption 
and  palatableness  it  may  form  a  useful  substitute  for  the  solid, 
non-nitrogenous  foodstuffs  in  sickness.  This  suggestion  seems 
to  be  supported  by  many  reports  of  cases  in  which  alcohol  has  served 
as  the  sole  or  main  nutriment  during  the  critical  periods  of  fevers 
and  in  other  conditions,  but  it  needs  to  be  tested  more  carefully  by 
direct  experiments  before  it  can  be  accepted  generally  for  prac- 
tical purposes.  In  line  with  this  suggestion  there  are  some 
results  upon  diabetic  patients  (Benedict  and  Torok)  which  indi- 
cate that  in  this  condition  alcohol  used  as  a  food  diminishes  the 
production  of  acetone  bodies  and  protects  the  protein. 

*  See  Miura,  "Zeitschrift  fur  klin,  Medicin,"  20,  1892. 
t  See  Rosemann,  "Archiv  f .  die  gesammte  Physiologic,"  86,  307, 1901,  and 
100,  348, 1903,  for  discussion  and  literature.    Also  "Handbuch  d.  Biochemie," 

i£ee  also  At  water  and  Benedict,  '  'Memoirs  of  National  Academy  of 
Sciences,"  1902;  and  Atwater,  "The  Nutritive  Value  of  Alcohol,"  in  "Physi- 
ological Aspects  of  the  Liquor  Problem,"  vol.  ii.,  1903. 


CHAPTER  L. 

EFFECT  OF  MUSCULAR  WORK  AND  TEMPERATURE  ON 

BODY  METABOLISM— HEAT  ENERGY  OF 

FOODS— DIETETICS. 

The  Effect  of  Muscular  Work. — It  is  a  matter  of  common 
knowledge  that  muscular  exercise  greatly  augments  the  physio- 
logical oxidations  as  measured  by  the  CO2  eliminated  and  the  heat 
produced  in  and  given  off  from  the  body.  This  general  fact  is  well 
illustrated  in  the  following  table:* 

Average  Normal  Output  of  Carbon  Dioxid  and  Heat  from  the  Body 

AVERAGE  QUANTITIES 

PER  HOUR. 
CARBON 

DIOXID,  HEAT, 

CONDITIONS  OP  MUSCULAR  ACTIVITY.  GM.  CALS. 

Man  at  rest,  sleeping 25  65 

Man  at  rest,  awake,  sitting  up 35  100 

Man  at  light  muscular  exercise 55  170 

Man  at  moderately  active  muscular  exercise 100  290 

Man  at  severe  muscular  exercise. 150  450 

Man  at  very  severe  muscular  exercise 210  600 

Physiologists  have  attempted  to  determine  which  of  our  energy- 
yielding  foodstuffs  is  directly  affected  by  muscular  activity.  A 
brief  statement  of  the  development  of  our  knowledge  upon  this 
point  will  make  clear  our  present  theories.  According  to  Liebig,  oui 
foods  fulfil  two  general  purposes  in  the  body :  they  are  burnt  to  sup- 
ply heat,  respiratory  foods — fats,  and  carbohydrates,  or  they  are 
used  to  construct  tissue,  plastic  foods — proteins.  It  seemed  to  fol- 
low, from  this  generalization,  that  muscular  tissue  in  activity  should 
use  protein  material,  and  it  was  believed  at  that  time  that  the  metab- 
olism of  protein  furnished  the  source  of  muscular  energy.  That  it  is 
not  the  sole  source  was  demonstrated  by  the  interesting  experiments 
of  Tick  and  Wislicenus.  These  physiologists  ascended  the  Faul- 
horn  to  a  height  of  1956  meters.  Knowing  the  weight  of  his  body, 
each  could  estimate  how  much  work  was  done  in  ascending  such 
a  height.  Fick's  weight,  for  example,  was  66  kilograms;  therefore 
in  climbing  the  mountain  he  performed  66X1956=129,096  kilo- 
grammeters  of  work.  In  addition,  the  work  of  the  heart  and  the 
respiratory  muscles,  which  could  not  be  determined  accurately, 
was  estimated  at  30,000  kilogrammeters.  There  was,  moreover, 

*  Benedict,  "Science,"  July  16,  1915. 
941 


942  NUTRITION    AND    HEAT  REGULATION. 

a  certain  amount  of  muscular  work  performed  in  the  move- 
ments of  the  arms  and  in  walking  upon  level  ground  that  was 
omitted  entirely  from  their  calculations.  For  seventeen  hours 
before  the  ascent,  during  the  climb  of  eight  hours,  and  for  six 
hours  afterward  their  food  was  entirely  non-nitrogenous,  so  that 
the  urea  eliminated  came  entirely  from  the  protein  of  the  body. 
Nevertheless,  when  the  urine  was  collected  and  the  urea  estimated, 
it  was  found  that  the  energy  contained  in  the  protein  destroyed, 
reckoned  as  heat  energy,  was  entirely  insufficient  to  account  for 
the  work  done.  Although  later  estimates  would  modify  somewhat 
the  actual  figures  of  their  calculation,  the  margin  was  so  great  that 
the  experiment  has  been  accepted  as  showing  conclusively  that  the 
total  energy  of  muscular  work  does  not  come  necessarily  from  the 
oxidation  of  protein.  Later  experiments  made  by  Voit  upon  a 
dog  working  in  a  tread-wheel  and  upon  a  man  performing  work 
while  in  the  respiratory  chamber  gave  the  surprising  result  that 
not  only  may  the  energy  of  muscular  work  be  far  greater  than  the 
heat  energy  of  the  protein  simultaneously  oxidized,  but  that  the 
performance  of  muscular  work  within  certain  limits  does  not 
affect  at  all  the  amount  of  protein  metabolized  in  the  body,  since 
the  output  of  urea  is  the  same  on  working  days  as  during  days  of 
rest.  Careful  experiments  by  an  English  physiologist,  Parkes,  made 
upon  soldiers,  while  resting  and  after  performing  long  marches, 
showed  also  that  there  is  no  distinct  increase  in  the  secretion  of  urea 
after  muscular  exercise.  It  followed  from  these  latter  experiments 
that  Liebig's  theory  as  to  the  source  of  the  energy  of  muscular 
work  is  incorrect,  and  that  the  increase  in  the  oxidations  in  the 
body,  which  undoubtedly  occurs  during  muscular  activity,  must  affect 
only  the  non-protein  material — that  is,  the  fats  and  carbohydrates. 
Subsequently  the  question  was  reopened  by  experiments  made 
under  Pfliiger  by  Argutinsky.*  In  these  experiments  the  total 
nitrogen  excreted  was  determined  with  especial  care  in  the  sweat 
as  well  as  in  the  urine  and  the  feces.  The  muscular  work  done 
consisted  in  long  walks  and  mountain  climbs.  Argutinsky  found 
that  work  caused  a  marked  increase  in  the  elimination  of  nitrogen, 
the  increase  extending  over  a  period  of  three  days,  and  he  estimated 
that  the  additional  protein  metabolized  in  consequence  of  the  work 
was  sufficient  to  account  for  most  of  the  energy  expended  in  per- 
forming the  walks  and  climbs.  A  number  of  objections  have  been 
made  to  Argutinsky 's  work.  It  has  been  asserted  that  during  his 
experiment  he  kept  himself  upon  a  diet  deficient  in  non-protein 
material,  and  that  if  the  supply  of  this  material  had  been  sufficient 
there  would  not  have  been  an  increase  in  protein  metabolism. 
These  experiments  were  repeated  in  various  forms  by  many  ob- 

*  Argutinsky,  "Pfliiger's  Archiv  f.  die  gesammte  Physiologie, "  46,  552, 
1890. 


EFFECT    OF    MUSCULAR    WORK    AND    TEMPERATURE.  943 

servers  (Zuntz,  Speck,  et  al),  and  the  general  result  has  been 
the  abandonment  of  both  the  former  views — the  Liebig  theory, 
that  the  energy  comes  only  from  the  consumption  of  protein,  and 
the  Voit  theory,  that  it  comes  only  from  the  oxidation  of  non-pro- 
tein material.  It  has  been  found  that  in  muscular  work  carried  to 
the  ordinary  extent  protein  material,  in  excess  of  that  destroyed  in 
conditions  of  rest,  may  or  may  not  be  used  according  to  the  amount 
of  fats  and  carbohydrates  contained  in  the  diet.  If  these  latter 
elements  are  in  sufficient  quantity  they  furnish  the  energy  required, 
and  the  protein  metabolism  is  not  increased  by  work.  If,  however, 
the  non-proteins  are  not  sufficient  in  quantity  some  of  the  energy 
is  obtained  at  the  expense  of  the  protein  of  the  body,  and  there  is 
an  increase  in  the  nitrogen  excretion.  We  may  believe,  in  fact, 
that  the  energy  necessary  for  muscular  work  may  be  obtained  from 
any  of  the  customary  foodstuffs — carbohydrates,  fat,  or  proteins. 
It  seems  probable  that  the  sugar  (glycogen)  of  the  muscle  is,  so  to 
speak,  the  easiest  source;  but,  when  the  carbohydrates  are  deficient 
or  absent  altogether  in  the  diet,  muscular  exercise  is  accompanied 
by  an  increase  in  the  consumption  of  fats  or  proteins  or  both. 
According  to  the  view  adopted  in  the  preceding  pages,  it  will  be  re- 
membered that  when  protein-food  is  used  as  a  source  of  energy 
the  nitrogen  is  split  off  in  the  tissues  by  the  process  of  deaminiza- 
tion  of  the  amino-acids.  According  to  this  view,  therefore,  the 
working  muscle  cells  obtain  their  energy  always  by  oxidation  of 
non-nitrogenous  material,  although  a  portion  of  this  material  may 
have  been  derived  ultimately  from  the  protein  of  the  food.  The 
Voit  theory  is  correct  to  the  extent  that  on  an  abundant  non-pro- 
tein diet  much  muscular  work  may  be  done  without  any  increase 
in  the  consumption  of  the  organized  protein  tissue.  The  muscle 
is  a  protein  machine  for  the  accomplishment  of  work,  but  in  the 
performance  of  moderate  work  there  is  apparently  no  greater 
wear  and  tear  of  the  machinery,  no  greater  tissue  waste,  than  under 
resting  conditions.  If,  however,  the  muscular  work  is  excessive, 
the  tissue  waste  may  be  increased.  Argutinsky  found  an  in- 
creased nitrogen  elimination  lasting  two  or  three  days  after  the 
cessation  of  the  work.  It  is  probable  that  this  result  indicates  a 
greater  waste  of  the  protein  apparatus  itself,  and  this  idea  is  borne 
out  by  the  fact  that  under  similar  conditions  other  observers  have 
detected  an  increase  in  the  creatinin  and  uric  acid  excretion, 
nitrogenous  wastes  that  are  derived  from  the  tissue  protein  of 
muscle.  The  effect  of  muscular  work  on  the  carbon  excretion,  car- 
bon dioxid,  is,  of  course,  marked  and  invariable.  Some  extra  ma- 
terial must  be  oxidized  to  furnish  the  energy,  and  since  this  material 
is  usually  sugar,  or  sugar  and  fat,  or  the  non-nitrogenous  portion 
of  the  protein  of  the  diet,  the  effect,  so  far  as  the  excretions  are  con- 
cerned, will  be  most  manifest  in  the  amount  of  carbon  dioxid 


944 


NUTRITION    AND    HEAT    REGULATION. 


given  off.     Pettenkofer  and  Voit  found  that  the  carbon  dioxid 

eliminated  by  a  man  during  a  day  of  work  was  nearly  double  that 
excreted  during  a  day  of  rest.  Along  with  this  rise  in  the  carbon 
dioxid  excretion  there  is  a  corresponding  increase  in  the  absorption 
of  oxygen.  These  results  are  well  illustrated  in  the  following 
table,  which  shows  the  effect  of  posture  and  of  severe  muscular 
work  upon  the  hourly  excretion  of  carbon  dioxid  and  absorption  of 
oxygen  (Benedict  and  Carpenter).* 


.  C02 

eliminated. 

O2 
absorbed. 

Heat 
produced. 

Man  at  rest,  sleeping 

Grams. 

23 

Grams. 
21 

Calories. 
71 

Man  at  rest,  sitting 

33 

27 

97 

Man  at  rest,  standing 

37 

31 

114 

Man  during  severe  work 

248 

213 

653 

Metabolism  During  Sleep. — It  has  been  shown  that  during 
sleep  there  is  no  marked  change  in  the  total  nitrogen  excreted, 
and  therefore  no  distinct  decrease  in  the  protein  metabolism. 
According  to  Siven,  there  is  a  distinct  diminution  in  the  secretion 
of  the  endogenous  purin  nitrogen.  On  the  contrary,  the  carbon 
dioxid  eliminated  and  the  oxygen  absorbed  are  unquestionably 
diminished.  This  latter  fact  finds  its  simplest  explanation  in  the 
supposition  that  the  muscles  are  less  active  during  sleep.  The 
muscles  do  less  work  in  the  way  of  contractions,  and,  in  addition, 
probably  suffer  a  diminution  in  tonicity,  which  also  affects  their 
total  metabolism. 

Effect  of  Variations  in  Temperature. — In  warm-blooded 
animals  variations  of  outside  temperature  within  ordinary  limits 
do  not  affect  the  body  temperature.  An  account  of  the  means  by 
which  this  regulation  is  effected  will  be  found  in  the  chapter  upon 
Animal  Heat.  So  long  as  the  temperature  of  the  body  remains  con- 
stant, it  has  been  found  that  a  fall  of  outside  temperature  may 
increase  the  oxidation  of  non-protein  material  in  the  body,  the  in- 
crease being  in  a  general  way  proportional  to  the  fall  in  tempera- 
ture. That  the  increased  oxidation  affects  the  non-protein  con- 
stituents is  shown  by  the  fact  that  the  nitrogenous  excreta  remain 
unchanged  in  quantity,  other  conditions  being  the  same,  while 
the  oxygen  consumption  and  the  carbon  dioxid  elimination  are 
increased.  This  effect  of  temperature  upon  the  body  metabolism 
is  due  mainly  to  a  reflex  stimulation  of  the  motor  nerves  to  the 
muscles.  The  temperature  nerves  of  the  skin  are  affected  by  a 
fall  in  outside  temperature,  and  bring  about  reflexly  an  increased 

*  Carnegie  Institution  of  Washington,  No.  126,  1910. 


EFFECT  OF  MUSCULAR  WORK  AND  TEMPERATURE.     945 

innervation  of  the  muscles  of  the  body.  Indeed,  it  is  stated* 
that  unless  the  lowering  of  the  temperature  is  sufficient  to  cause 
shivering  or  muscular  tension  no  increase  in  the  excretion  of  CO2 
results.  This  fact  suffices  to  explain,  therefore,  the  physiological 
value  of  shivering  and  muscular  restlessness  when  the  outside 
temperature  is  low.  The  fact  that  variations  in  outside  tempera- 
ture affect  only  the  consumption  of  non-protein  material  falls  in, 
therefore,  with  the  conception  of  the  nature  of  the  metabolism 
of  muscle  in  activity,  given  above.  When  the  means  of  regulating 
the  body  temperature  break  down  from  too  long  an  exposure  to 
excessively  low  or  excessively  high  temperatures,  the  total  body 
metabolism,  protein  as  well  as  non-protein,  increases  with  a  rise 
in  body  temperature  and  decreases  with  a  fall  in  temperature.  In 
fevers  arising  from  pathological  causes  it  has  been  shown  that  there 
is  an  increased  excretion  of  nitrogen  as  well  as  of  carbon  dioxid. 

Effect  of  Starvation. — A  starving  animal  must  live  upon  the 
material  present  in  its  body.  This  material  consists  of  the  fat 
stored  up,  the  circulating  and  tissue  protein,  and  the  glycogen. 
The  latter,  which  is  present  in  comparatively  small  quantities,  is 
quickly  used,  disappearing  more  or  less  rapidly  according  to  the 
extent  of  muscular  movements  made.  Thereafter  the  animal  lives 
on  its  own  protein  and  fat,  and  if  the  starvation  is  continued  to  a 
fatal  termination  the  body  becomes  correspondingly  emaciated. 
Examination  of  the  several  tissues  in  animals  starved  to  death  has 
brought  out  some  interesting  facts.  Voit  took  two  cats  of  nearly 
equal  weight,  fed  them  equally  for  ten  days,  and  then  killed  one  to 
serve  as  a  standard  for  comparison  and  starved  the  other  for  thirteen 
days;  the  latter  animal  lost  1017  gms.  in  weight,  and  the  loss  was 
divided  as  follows  among  the  different  organs: 

Loss  TO 

SUPPOSED  WEIGHT      ACTUAL  LOBS       EACH  100  GMS. 
OF  ORGANS  BEFORE         OF  ORGANS        OF  FRESH  ORGAN 
STARVATION.  IN  GMS.       (PERCENTAGE  Loss) 

Bone 393.4  54.7  13.9 

Muscle 1408.4  429.4  30.5 

Liver 91.9  49.4  53.7 

Kidney 25.1  6.5  25.9 

Spleen 8.7  5.8  66.7 

Pancreas 6.5  1.1  17.0 

Testes 2.5  1.0  40.0 

Lungs 15.8  2.8  17.7 

Heart 11.5  0.3  2.6 

Intestines   118.0  20.9  18.0 

Brain  and  cord 40.7  1.3  3.2 

Skin  and  hair 432.8  89.3  20.6 

Fat 275.4  267.2  97  0 

Blood 138.5  37.3  27.0 

Remainder 136.0  50.0  36.8 

According  to  these  results,  the  greatest  absolute  loss  was  in  the 
muscles  (429  gms.),  while  the  greatest  percentage  loss  was  in  the  fat 
*  Johannson,  "Skandinavisches  Archiv  f.  Physiologie,"  7,  123,  1897 
60 


946  NUTRITION    AND   HEAT    REGULATION. 

(97  per  cent.),  which  had  practically  disappeared  from  the  body. 
It  is  very  significant  that  the  central  nervous  system  and  the  heart^ 
organs  which  we  may  suppose  were  in  continual  activity,  suffered 
practically  no  loss  of  weight:  they  had  lived  at  the  expense  of  the 
other  tissues.  We  must  suppose  that  in  a  starving  animal  the  fat 
and  the  protein  materials,  particularly  in  the  voluntary  muscles, 
pass  into  solution  in  the  blood,  probably  as  a  result  of  intra- 
cellular  digestion  (autolysis),  and  are  then  used  to  nourish  the 
tissues  generally  and  to  supply  the  heat  necessary  to  maintain  the 
body  temperature.  Examination  of  the  excreta  in  starving  ani- 
mals has  shown  that  a  greater  quantity  of  protein  is  destroyed  dur- 
ing the  first  day  or  two  than  in  the  subsequent  days.  This  fact 
is  explained  on  the  supposition  that  the  body  is  at  first  supplied 
with  a  certain  excess  of  protein  material,  circulating  protein,  de- 
rived from  its  previous  food,  and  that  after  this  is  metabolized 
the  animal  lives  entirely,  so  far  as  protein  consumption  is  con- 
cerned, upon  its  "tissue  protein."  If  the  animal  remains  quiet 
during  starvation,  the  amount  of  nitrogen  excreted  daily  soon 
reaches  a  nearly  constant  minimum,  showing  that  a  •  practically 
constant  amount  of  protein  (together  with  fat)  is  consumed  daily 
to  furnish  body  heat,  and  material  for  the  energy  needs  and  tissue 
waste  in  the  active  organs,  such  as  the  heart.  Shortly  before 
death  from  starvation  the  daily  amount  of  protein  consumed  may 
increase,  as  shown  by  the  larger  amount  of  nitrogen  eliminated. 
This  fact  is  explained  by  assuming  that  the  body  fat  is  then  ex- 
hausted and  the  animal's  metabolism  is  confined  to  the  tissue 
proteins  alone.  The  general  fact  that  the  loss  of  protein  is  greatest 
during  the  first  one  or  two  days  of  starvation  has  been  confirmed 
upon  men  in  a  number  of  interesting  experiments  made  upon 
professional  fasters.  For  the  numerous  details  as  to  loss  of  weight, 
variations  of  temperature,  etc.,  carefully  recorded  in  these  latter 
experiments,  reference  must  be  made  to  original  sources*  It  may 
be  added,  in  conclusion,  that  the  fatter  the  body  is,  to  begin  with, 
the  longer  will  starvation  be  endured,  and  if  water  is  consumed 
freely  the  evil  effects  of  starvation,  as  well  as  the  disagreeable 
sensations  of  hunger,  are  very  much  reduced. 

The  Potential  Energy  of  Food. — The  food  material  during 
digestion  and  after  absorption  undergoes  numerous  chemical 
changes  in  the  body.  Some  of  these  changes  are  not  attended  by 
the  liberation  of  heat  to  any  marked  extent.  Such  is  the  case,  for 
instance,  with  the  hydrolytic  cleavages  of  the  molecule  which 
have  been  described  especially  in  connection  with  the  digestive 

*"Virchow's  Archiv,"  vol.  131,  supplement,  1893;  and  Luciani,  "Das 
Hungern,"  1890.  See  also  Weber,  "Ergebnesse  der  Physiologic,"  vol.  i.,  part  i., 
1902;  Benedict,  "A  Study  of  Prolonged  Fasting,"  Carnegie  Institution,  No. 
203,  1915. 


POTENTIAL    ENERGY    OF    FOOD.  947 

processes.  As  an  example  of  this  fact  one  may  take  the  inversion 
of  the  double  sugars — one  molecule  of  maltose  yields  two  molecules 
of  dextrose.  The  heat  value  of  a  gram  molecule  of  maltose  is 
1350.7  calories.  The  heat  value  of  the  dextrose  resulting  from  its 
inversion  is  1347.4  cal.,  so  that  the  process  of  hydrolysis  liberates 
only  3.3  cal.  or  about  0.2  per  cent,  of  the  total  available  energy  in 
the  maltose,  f  Similar  hydrolytic  cleavages  occur  doubtless  within 
the  tissues,  and  other  changes  connected  with  muscular,  nervous, 
and  glandular  activity,  and  the  building  up  and  breaking  down 
of  the  living  substance  take  place  constantly  as  a  part  of  general 
nutritional  metabolism.  On  the  other  hand,  many  of  the  chemical 
processes  occurring  in  the  body  are  especially  valuable  on  account 
of  the  heat  liberated.  These  reactions,  for  the  most  part,  at 
least,  are  oxidations;  they  are  effected  under  the  influence  of 
oxidizing  enzymes  or  by  some  other  means  of  activating  the 
oxygen.  The  various  stages  in  the  process  are  not  explained, 
but  we  know  that  oxygen  is  necessary  and  that  the  carbon  and 
the  hydrogen  contained  in  the  substances  acted  upon  appear 
eventually  in  the  form  of  oxidation  products — namely,  carbon 
dioxid  and  water — Liebig  designated  the  fats  and  carbohydrates 
as  respiratory  foods  on  the  hypothesis  that  their  fate  in  the  body 
is  to  be  oxidized  and  furnish  heat.  While  this  view  is,  in  the 
main,  correct,  it  is  evident  now  that  a  portion  at  least  of  the 
protein  molecule,  after  the  splitting  off  of  the  nitrogen,  may 
also  undergo  oxidation  and  furnish  heat.  In  Liebig's  sense, 
therefore,  the  proteins  play  the  part  of  respiratory  or  heat-pro- 
ducing foods  as  well  as  acting  as  tissue  formers.  On  the  other 
hand,  fats  and  carbohydrate  material  may  enter  to  some  extent, 
together  with  the  protein,  into  the  synthesis  of  cell  material,  and 
thus  play  the  role  of  a  plastic  or  tissue-forming  as  well  as  of  a 
respiratory  food.  We  cannot  divide  the  foodstuffs,  therefore, 
strictly  into  two  such  classes,  but  we  may  perhaps  consider  the 
chemical  processes  in  the  body  under  the  two  heads  mentioned 
above,  namely,  the  oxidation  or  heat-producing  changes  and  those 
due  to  hydrolytic  cleavages,  synthesis,  etc.,  which  are  attended  by 
a  small  liberation  of  heat,  or,  indeed,  may  be  accompanied  by  an  ab- 
sorption of  energy  (synthesis).  The  great  supply  of  heat  energy 
needed  by  the  body  to  maintain  its  temperature  comes  from  the 
oxidation  processes.  The  heat  produced  in  and  given  off  from  the 
body  is  estimated  in  terms  of  calories.  The  small  calorie  (c)  or 
gram-calorie  is  the  quantity  of  heat  necessary  to  raise  one  gram 
of  water  one  degree  centigrade  in  temperature,  while  the  large 
calorie  (C)  or  kilogram-calorie  is  the  quantity  of  heat  necessary 

*  See  Herzog,  "Zeit.  f.  physiol.  chem.,"  37,  383, 1903,  and  Tangl,  "Pfliiger's 
Archiv,"  115,  1,  1906. 


948  NUfRITION   AND    HEAT    REGULATION. 

to  raise  the  temperature  of  one  thousand  grams  of  water  one  de- 
gree. In  round  numbers  an  adult  man  produces  in  his  body  and 
gives  off  to  the  surrounding  air  about  2,400,000  calories  (2400  C.) 
of  heat  per  day.  This  great  supply  of  heat  is  derived  from  the 
physiological  oxidation  of  the  carbohydrate,  fat,  and  protein 
material  of  the  food.  These  same  materials  may  be  oxidized 
outside  the  body  by  burning  them  at  a  high  temperature  or  under 
a  high  pressure  of  oxygen,  and  the  heat  that  they  give  off  in  the 
process  can  be  measurerd  directly.  So  far  as  the  fats  and  carbo- 
hydrates are  concerned,  the  end-products  of  the  oxidation  in  the 
body  are  the  same  as  in  their  combustion  out  of  the  body,  and  we 
may  believe,  therefore,  that  the  amount  of  heat  produced  is  the 
same  in  both  cases.  Consequently  the  heat  value  of  a  gram  of  fat 
or  carbohydrate  burnt  outside  the  body  is  spoken  of  as  its  combus- 
tion equivalent,  and  it  measures  the  amount  of  potential  energy 
of  these  foodstuffs  which  is  available  for  the  production  of  heat 
or  for  the  supply  of  energy  in  other  forms  to  the  working  cells.. 
With  regard  to  the  protein,  the  case  is  somewhat  different.  Its 
end-products  in  the  body  are  carbon  dioxid,  water,  and  urea 
or  some  other  of  the  nitrogenous  waste  products.  These  nitrog- 
enous wastes  are  capable  of  further  oxidation  with  liberation 
of  heat,  so  that,  as  far  as  they  are  eliminated,  the  body 
loses  a  possible  supply  of  heat  energy,  which  must  be  subtracted 
from  the  total  heat  energy  that  the  protein  gives  upon  oxida- 
tion outside  the  body,  in  order  to  determine  the  available  heat 
energy  yielded  within  the  body.  The  figures  obtained  for  the  heat 
equivalents  of  the  foodstuffs  by  burning  them  outside  the  body  in 
some  form  of  calorimeter  are  as  follows :  1  gm.  of  fat  yields  an  aver- 
age of  9300  calories,  or  9.3  large  calories  (C),  1  gm.  of  carbohydrate 
yields  an  average  of  4100  calories  (4.1  C.).  These  figures  may  be 
taken,  therefore,  to  express  the  quantity  of  heat  given  to  the  body 
by  the  oxidation  within  its  tissues  of  these  elements  of  our  food. 
A  gram  of  protein  when  burnt  outside  of  the  body  yields  on  the  aver- 
age 5778  calories.  The  heat  value  of  the  urea  is  estimated  as  1 
gm.  =  2523  calories.  If  we  assume  that  all  the  nitrogen  of  the  pro- 
tein appears  as  urea  and  that  1  gm.  of  protein  yields  J  gm.  of  urea, 
then  the  available  heat  energy  of  a  gram  of  protein  should  be  equal 
to  5778  —  841  (or  J  of  2523)  =  4937  calories.  Later  workers,  however, 
have  given  reasons  for  believing  that  this  last  figure  is  too  high. 
All  of  the  nitrogen  is  not  eliminated  as  urea,  and,  moreover,  all  of 
the  nitrogenous  waste  is  not  excreted  in  the  urine;  a  distinct  pro- 
portion is  given  off  in  the  feces.  Rubner.has  calculated  the  avail- 
able heat  energy  of  proteins  by  direct  experiments  upon  animals. 
In  these  experiments  the  heat  value  of  the  protein  fed  was  directly 
determined  by  burning  a  sample  in  a  calorimeter.  Then  after  feed- 


POTENTIAL    ENERGY    OF    FOOD.  949 

ing  a  known  amount  of  the  protein  the  urine  and  feces  were  col- 
lected and  their  heat  value  was  determined  in  the  same  way.  The 
difference  between  the  total  heat  value  of  the  protein  fed  and  the 
heat  value  lost  in  its  excreted  products  in  the  feces  and  urine  gave 
the  actual  heat  energy  obtained  from  the  protein  by  the  animal 
body.  Results  obtained  by  this  method  give  an  average  value 
for  1  gm.  protein  of  4100  calories  (4.1  C.),  or,  since  protein  contains 
an  average  of  16  per  cent,  of  nitrogen,  we  may  say  that  1  gm.  of  ni- 
trogen ingested  as  protein  has  a  heat  value  of  4.1  X  6.25  =  25.6  C. 
The  figures  that  are  used,  therefore,  in  estimating  the  heat  value 
of  our  foodstuffs  are: 

1  gm.  protein  =  4100  calories  (4.1  C.). 

1  gm.  carbohydrate  (starch)  =  4100  calories  (4.1  C.I. 
1  gm.  fat  =  9305  calories  (9.3  C.). 

Making  use  of  these  values,  it  is  obvious  that  we  can  calculate  the 
total  heat  value  of  any  given  diet.  If  we  analyze  the  food  for  its 
composition  in  the  three  principal  foodstuffs  we  may  determine  how 
many  calories  will  be  furnished  to  the  body.  In  many  of  the  tables 
published  to  show  the  composition  of  the  different  foods  figures  are 
given  also  to  express  their  heat  value  or  potential  energy,  since 
these  substances  taken  into  the  body  as  food  leave  it  in  the  form  of 
water,  carbon  dioxid,  and  urea  (or  one  of  the  related  nitrogenous 
excreta).  So  that  all  of  the  potential  chemical  energy  contained 
in  them  that  can  be  liberated  by  oxidation  to  these  stages  must 
have  been  set  free  in  the  body  in  one  form  or  another.  It  is  con- 
venient to  express  this  total  liberation  of  energy  in  terms  of  its 
heat  equivalent.  Indeed,  for  the  most  part,  the  potential  chemical 
energy  of  the  food  does  take  the  form  of  heat,  mediately  or  im- 
mediately, as  the  result  of  the  processes  going  on  in  the  tissues, 
and  in  this  form  it  is  given  off  from  the  body  to  the  external  world. 
No  measurable  amount  of  energy  is  given  off  from  the  body  except 
as  heat  and  mechanical  work.  When  the  body  is  at  rest  all  of  the 
energy  is  given  off  as  heat,  and  if  this  is  measured  in  calories  it  will 
be  found  to  equal  the  heat  equivalent  of  the  proteins,  fats,  and 
carbohydrates  oxidized  in  the  body  during  the  period  of  obser- 
vation. The  values  for  some  of  our  ordinary  foods  are  shown  in 
table  on  page  950.* 

It  must  be  borne  in  mind,  however,  that  the  entire  nutritional 
value  of  a  food  is  not  expressed  in  its  heat  value.  Some  of  our 
food  material — the  green  foods  and  fruits,  for  example — are  useful 
and  in  a  measure  essential  because  of  their  salts  and  organic  acids, 
in  spite  of  the  fact  that  they  contain  but  little  energy  that  can 
be  utilized  by  the  body.  Moreover,  recent  work,  already  referred 

*  Selected  from  Atwater  and  Bryant,  Bulletin  28  (revised  edition),  United 
States  Department  of  Agriculture,  1889. 


950 


NUTRITION    AND    HEAT    REGULATION. 


PROTEIN 

fi                                                                          V  ALiUJu 

.  FAT.     ^A*           "    ASH.        IN  CALORIES 

DRATE. 

PER  POUND. 

Beefsteak,  porterhouse  

.    19.1 

17.9 

0.8 

1110 

Beefsteak,  round  (lean)  

..    20.2 

2.4 

1.2 

475 

Corned  beef  (canned)  

..    26.3 

18.7 

4.0 

1280 

Veal,  leg  (lean)  

..    19.4 

3.7 

1.1 

520 

Veal  liver  

..    19.0 

5.3 

1.3 

575 

Mutton,  leg  (lean)  

.  .    16.5 

10.3 

0.9 

740 

Pork,  ham  (fresh,  lean)  

.  .    24.8 

14.2 

1.3 

1060 

Pork  chops,  medium  fat  

..    13.4 

24.2 

0.8 

1270 

Chicken  (fowl)  

..    13.7 

12.3 

0.7 

775 

Shad  

..     9.4 

4.8 

0.7 

380 

Shad  roe  

..    20.9 

3.8         2.6 

1.5 

600 

Eggs 

..    11.7 

10.7        

0.7 

680 

Milk 

..      3.3 

4.0         5.0 

0.7 

325 

Oatmeal  

..    16.1 

7.2       67.5 

1.9 

1860 

Rice  

..      8.0 

0.3       79.0 

0.4 

1630 

Wheat  flour  (entire  wheat) 

.  .  13.8 

1.9       71.9 

1.0 

1675 

Green  peas  

..      7.0 

0.5        16.9 

1.0 

465 

Potatoes  (raw)  

..      2.2 

0.1        18.4 

1.0 

385 

Spinach  

..      2.1 

0.3         3.2 

2.1 

110 

Tomatoes  

..      0.9 

0.4         3.9 

0.5 

105 

Apples  

..      0.4 

0.5        14.2 

0.3 

290 

Bananas  

..      1.3 

0.6       22.0 

0.8 

460 

to  (p.  911),  makes  it  increasingly  probable  that  the  different 
proteins  or  even  the  different  carbohydrates  or  fats  may  be  found 
to  have  each  a  specific  influence  upon  metabolism.  And,  lastly, 
specific  substances  may  be  found  in  the  foods  (food  accessories  or 
vitamines),  which  in  some  as  yet  undetermined  way  are  important 
or  essential  to  the  metabolism  of  some  part  of  the  body.  In  these 
respects  the  science  of  dietetics  has  a  wide  field  for  investigation.  In 
a  general  way,  however,  the  heat  energy  of  a  food  expresses  its  value 
as  a  means  for  supplying  the  energy  needs  of  the  living  cells.  In  the 
work  that  these  cells  perform,  whether  it  is  contraction,  secretion, 
or  nervous  activity,  energy  is  needed,  and  this  energy  is  carried 
into  the  body  in  the  potential  chemical  energy  of  the  proteins,  fats, 
and  carbohydrates,  whatever  may  be  the  source  from  which  these 
foodstuffs  are  obtained. 

Dietetics. — The  subject  of  the  proper  nourishment  of  individ- 
uals or  collection  of  individuals  in  health  and  in  sickness  is  treated 
usually  in  works  upon  hygiene  or  dietetics.  The  practical  details 
of  the  preparation  and  composition  of  diets  must  be  obtained 
from  such  sources.*  The  general  principles  upon  which  practical 
dieting  depends  have  been  obtained,  however,  from  experimental 
work  upon  the  nutrition  of  man  and  the  lower  animals,  some 
account  of  which  has  been  given  in  the  foregoing  pages.  In  a 

*  For  practical  directions,  see  Gautier,  "I/ alimentation  et  les  regimes," 
1904;  Blyth,  "Foods:  their  Composition  and  Analysis  ";  Rose,  "Feeding  the 
Family,"  New  York,  1916. 


DIETETICS.  951 

healthy  adult  the  main  objects  of  a  diet  are  to  furnish  sufficient 
nitrogenous  and  non-nitrogenous  foodstuffs,  salts,  and  water  to 
maintain  the  body  in  an  equilibrium  of  material  and  of  energy— 
that  is,  the  diet  must  furnish  the  material  for  the  regeneration  of 
tissue  and  the  material  for  the  heat  produced  and  the  muscular 
work  and  other  work  done.  The  functions  of  a  diet  are  accom- 
plished most  easily  and  most  economically  when  it  consists  of  pro- 
teins and  fats,  or  proteins  and  carbohydrates,  or,  as  is  almost  uni- 
versally the  case,  of  proteins,  fats,  and  carbohydrates,  together 
with  an  adequate  quantity  of  water,  the  necessary  inorganic  salts, 
and  the  newly  discovered  food  accessories  (vitamines).  The  expe- 
rience of  mankind  shows  that  such  a  mixed  diet  is  most  beneficial 
to  the  body  and  most  satisfying  to  that  valuable  regulating  mech- 
anism of  nutrition,  the  appetite.  Expressed  in  its  most  general 
form  the  cells  of  our  body  need  food  for  two  purposes:  First,  to 
supply  the  energy  needs;  second,  to  furnish  the  material  for  the 
construction  of  their  own  living  substance,  that  is,  for  assimilation. 
The  first  of  these  purposes  is  fulfilled  by  any  of  the  three  energy- 
yielding  foodstuffs,  carbohydrates,  fats,  or  proteins,  but  as  a  matter 
of  fact  we  use  chiefly  the  carbohydrates  on  account  of  their  economy 
and  the  ease  with  which  they  are  utilized  by  the  body.  For  the 
second  purpose,  the  construction  of  protoplasm  or  living  matter 
proteins  (or  their  cleavage  products,  the  various  amino-bodies)  are 
absolutely  necessary,  and  also  probably  an  adequate  supply  of 
inorganic  salts  and  the  so-called  accessories  (vitamines).  In  accord- 
ance with  this  specific  and  necessary  function  of  the  protein  we  find 
that  the  amount  used  in  the  daily  diet  is  fairly  constant,  about  100 
gms.,  while  the  proportions  of  fat  and  carbohydrate  show  wide 
variations.  Since  from  the  energy  standpoint  the  fats  and  carbo- 
hydrates have  a  common  function,  serving  as  fuel  for  the  energy 
needs  of  the  body,  we  ought  to  be  able  to  exchange  them  in  the 
diet  in  the  ratio  of  their  heat  values. 

This  ratio,  or  as  it  is  frequently  called,  the  isodynamic  equiva- 
lent, is  as  9.3  to  4.1  or  2.3  to  1,  and  within  the  limits  permitted  by 
the  appetite  we  should  be  able  to  substitute  1  part  of  fat  for  2.3 
parts  of  sugar  or  starch.  Experiments  upon  animals,  as  well  as 
the  experience  of  mankind,  show  that  this  substitution  can  be 
made,  although  it  is  not  advisable  to  eliminate  either  of  these 
foodstuffs  entirely  from  the  diet.  The  fact  that  within  certain 
limits  fats  and  carbohydrates  may  be  substituted  for  each  other 
is  illustrated  in  a  general  way  by  the  different  diets  recom- 
mended by  various  physiologists,  since  it  will  be  noticed  that  in 
those  in  which  the  proportion  of  fat  is  large  the  amount  of  carbo- 
hydrate is  reduced. 


952  NUTRITION    AND    HEAT    REGULATION. 

AVERAGE  DIETS  AND  THEIR  HEAT  VALUES. 

MOLESCHOTT.  RANKE.  VoiT. 

CALORIES.  CALORIES.  CALORIES. 

Protein 130  gms.  ...  533  100  gms.  ...  410  118  gms.  ...  483 

Fats 40   "   ...  372  100  "   ...  930  56  '   ...  520 

Carbohydrates  ...  550  "   .  .  .  2275  240  '   .  .  .  984  500  '   .  .  .  2050 

2980  2324  3053 

FORSTER.  ATWATER. 

CALORIES.  CALORIES. 

Protein     ......  131  gms.  ...      567  125  gms 512 

Fats 68     "...      632  125     "     ....   1172 

Carbohydrates  .  .   .  494     "      .   .    -J.825  400     "...   .    1640 

2024  3324 

The  average  heat  value  of  these  diets  is  equal  to  2742  calories, 
of  which  about  18  per  cent,  is  furnished  by  the  protein.  Generally 
speaking,  it  will  be  found  that  in  the  dietaries  selected  voluntarily 
by  mankind  the  protein  furnishes  from  15  to  20  per  cent,  of  the 
total  heat  value  of  the  diet.  According  to  some  physiologists 
this  proportion  is  unnecessarily  large  and  it  might  be  reduced 
to  as  little  as  5  or  10  per  cent.  Whether  or  not  such  a  change  is 
justified  has  already  been  discussed  to  some  extent  (p.  906). 
Leaving  aside  this  point,  it  is  usually  estimated  in  round  num- 
bers that  the  diet  should  furnish  daily  2400  Calories  for  an  in- 
dividual weighing  60  kgms.,  when  doing  no  muscular  work,  or 
about  40  Calories  per  kgm.  of  body  weight.  It  will  be  noticed 
that  in  all  cases  the  greatest  portion  of  this  energy  is  obtained 
from  the  carbohydrate  food,  which,  on  account  of  its  economy, 
its  abundance,  and  its  ease  of  digestion  and  oxidation  in  the 
body,  constitutes  the  bulk  of  our  diet.  In  cases  of  excessive 
muscular  work  the  food  eaten  may  supply  more  than  twice  the 
average  heat  value  given  above.  Thus,  Atwater  and  Sherman 
estimate  that  in  a  six-day  bicycle  race  by  professionals  the  heat 
value  of  the  food  for  the  different  participants  varied  from  4770 
to  6095  Calories.  Chittenden,  in  the  work  previously  referred 
to,*  has  raised  the  question  whether  the  heat  value  of  the  diet 
ordinarily  employed  is  unnecessarily  high.  In  his  own  case  he 
found  that  the  body  could  be  well  nourished  on  a  diet  contain- 
ing a  total  heat  value  of  only  1600  Calories  or  28  Calories  per  kgm. 
of  body  weight  instead  of  40  Calories.  The  diet  in  this  case, 
it  will  be  remembered,  contained  only  36  to  40  gms.  of  protein 
in  place  of  the  100  to  130  gms.  recommended  in  the  diets  mentioned 
above.  The  question  thus  raised  is  one  that  must  be  decided  by 
actual  experience,  but  from  the  numerous  statistical  and  experi- 
mental results  now  availablef  it  would  appear,  as  has  been  stated 
above,  that  the  total  energy  necessary  in  a  diet,  estimated  in 

*  Chittenden,  "Physiological  Economy  in  Nutrition,"  1905. 

*  See   especially  the  numerous  Bulletins   of  the   U.  S.  Department   of 
Agriculture,  Nos.  28,  116,  129,  149,  etc. 


DIETETICS.  953 

terms  of  its  heat  value,  varies  chiefly  with  the  amount  of  muscular 
work  to  be  done.  Persons  who  lead  a  very  muscular  life  require 
a  correspondingly  large  amount  of  energy  in  the  diet,  and  this 
demand  is  met  usually  by  augmenting  the  proportion  of  carbo- 
hydrate and  fat,  especially  the  carbohydrate.  Since  the  amount 
of  protein  is  not  varied  greatly  in  such  cases  the  diet  is  relatively 
poor  in  this  foodstuff.  On  the  contrary,  those  who  lead  a  sedentary 
life,  including,  broadly  speaking,  all  the  well-to-do  class,  require 
less  energy  in  their  diet,  and  they  can  afford  to  reduce  the  pro- 
portion of  carbohydrate  and  fat.  The  diet  in  such  cases  may  be 
relatively  rich  in  protein,  although  the  amount  per  kilogram  of 
body  weight  is  not  increased,  in  fact,  is  usually  diminished  some- 
what. These  facts  are  illustrated  in  Atwater's  estimate  of  the 
diet  necessary  for  men  performing  different  amounts  of  muscular 
work. 

PROTEIN.         CARBOHYDRATE 
AND  FAT. 

Man  doing  hard  muscular  work 600  cal.  3550  cal. 

Man  doing  moderate  muscular  work 500    "  2900    ; 

Man  doing  no  muscular  work 360    '  2040    ' 

On  comparing  these  diets  it  will  be  observed  that  in  per- 
forming hard  muscular  work  the  diet  contained  1700  Calories  of 
energy  beyond  that  used  when  no  work  was  done.  About  six- 
sevenths  of  this  increase  was  provided  for  by  the  carbohydrates 
and  fats.  It  will  be  seen  also  that  in  this  case  the  proportion 
of  the  total  energy  obtained  from  protein  remained  practically 
unchanged. 

In  the  dietetics  of  large  groups  of  persons,  that  of  a  nation, 
for  example,  it  is  important  to  know  not  only  the  amount  of  energy 
needed  daily  by  each  individual  and  the  proportion  of  this  energy 
that  should  be  obtained  respectively  from  proteins,  fats,  and  carbo- 
hydrates, but  also  from  what  naturally  occurring  foods  these 
supplies  of  energy  are  actually  drawn.  Thus  in  an  interesting 
report  published  by  an  English  commission  it  is  shown  that  in 
Great  "Britain  in  the  years  1909-13,  30.8  per  cent,  of  the  energy 
in  the  diets  of  the  inhabitants  was  derived  from  wheat  alone. 
Meat  furnished  17.4  per  cent.;  sugar,  13  per  cent.,  and  fish,  only 
1  per  cent.* 

Munk  gives  an  interesting  table  showing  how  much  of  certain 
familiar  articles  of  food  would  be  necessary,  if  taken  alone,  to  supply 
the  requisite  daily  amount  of  protein  or  non-protein  material;  his 
estimates  are  based  upon  the  percentage  composition  of  the  foods 
and  upon  experimental  data  showing  the  extent  of  absorption  of  the 

*  See  Lusk,  "Science,"  April  13,  1917. 


954  NUTRITION    AND    HEAT    REGULATION. 

foodstuffs  in  each  food.  In  this  table  be  supposes  that  the  daily 
diet  should  contain  110  gms.  of  protein  =  17.5  gms.  of  N,  and  non- 
proteins  sufficient  to  contain  270  gms.  of  C: 

FOR  110  GMS.  PROTEDC        -p      0_n  ^       fx 
(17.5  GMS.  N).  FoR  27°  GMS-  °- 

Milk 2900  gms.  3800  gms. 

Meat  (lean) 540     "  2000     " 

Hen's  eggs 18  eggs.  37  eggs. 

Wheat  flour 800  gms.  670  gms. 


Wheat  bread 1650 

Rye  bread 1900 

Rice 1870 

Corn 990 

Peas 520 

Potatoes..  4500 


1000 
1100 
750 
660 
750 
2550 


As  Munk  points  out,  this  table  shows  that  any  single  food,  if  taken 
in  quantities  sufficient  to  supply  the  nitrogen,  would  give  too  much 
or  too  little  carbon  and  the  reverse;  those  animal  foods  which,  in 
certain  amounts,  supply  the  nitrogen  needed  furnish  only  from  one- 
fourth  to  two-thirds  of  the  necessary  amount  of  carbon  and,  vice 
versa,  the  vegetable  foods  if  taken  in  sufficient  quantity  to  supply 
the  carbon  would  not  give  sufficient  nitrogen,  or  if  used  alone  to 
furnish  the  requisite  nitrogen  would  give  an  excess  of  carbon. 
This  same  fact  is  illustrated  in  another  way  in  a  table  compiled 
by  Cohnheim.*  To  furnish  the  body  with  its  necessary  daily 
quota  of  100  grams  of  protein  the  following  amounts  of  different 
foods,  expressed  in  their  heat  values,  would  be  required: 

Meat 495  Coarse  bread 4552 

Eggs 1133  Fine  bread 4720 

Cheese 1704  Potatoes 5000 

Milk 2070  Rice 5600 

Corn 4104 

It  is  evident  from  this  table  that  a  person  leading  a  sedentary 
life  who  used  a  vegetable  diet  alone  would  be  required,  in  order  to 
obtain  his  necessary  protein,  to  consume  much  more  carbohy- 
drate than  from  an  energy  standpoint  was  needed  by  the  body. 
As  Cohnheim  points  out,  the  animal  foods  are  for  this  reason  espe- 
cially suited  to  supply  the  protein  needs  of  those  who  lead  a  com- 
paratively inactive  life.  In  practical  dieting  we  are  accustomed 
to  get  our  supply  of  proteins,  fats,  and  carbohydrates  from  both 
vegetable  and  animal  foods.  To  illustrate  this  fact  by  an  actual 
case,  in  which  the  food  was  carefully  analyzed,  an  experimenter 
weighing  67  kgms.  records  that  he  kept  himself  in  nitrogen  equilib- 
rium upon  a  diet  in  which  the  protein  was  distributed  as  follows: 

*  Cohnheim,  "Die  Physiologic  der  Verdauung  und  Ernahrung,"  1908. 


DIETETICS. 


955 


300     gms.  meat  =  63.08  gms.  protein  =  9.78    gms.  N. 

666.3  c.c.  milk  =  18.74     "          "  =  2.905     "      " 

100     gms.  rice  =  7.74     "          "  =  1.2         "      " 

100        "     bread  =  11.32     "          "  =  1.755     "      " 

500     c.c.  wine  =  1.17     "  =  0.182  gm.     " 

102.05     "          "  =      15.868  gms.  " 

For  a  person  in  health  and  leading  an  active,  normal  life,  appetite 
and  experience  seem  to  be  safe  and  sufficient  guides  by  which  to 
control  the  diet:  they  may  b£  relied  upon,  at  least,  to  protect  the 
body  from  undernutrition.  The  opposite  danger  of  overeating 
is  a  real  one,  particularly  among  those  who  do  not  lead  an  active 
life.  It  is,  however,  a  hygienic  offence  that  is  usually  committed 
knowingly  and  may  consequently  be  controlled  by  those  who  have 
sufficient  wisdom.  Physiological  knowledge  emphasizes  clearly 
enough  the  great  fact  that  the  mechanisms  of  nutrition  and 
digestion,  like  the  other  mechanisms  of  the  body,  should  not  be 
subjected  to  unnecessary  strain.  For  those  who  are  in  health, 
the  important  rule  to  follow  in  the  matter  of  diet  is  to  avoid  an 
excess  in  eating.  In  conditions  of  disease,  in  regulating  the  diet 
of  children  or  of  collections  of  individuals,  as  in  the  army,  navy, 
etc.,  it  is  necessary  for  purposes  of  hygiene  or  for  purposes  of 
economy  to  arrange  the  diet  in  accordance  with  the  knowledge 
obtained  from  experience  and  from  scientific  investigations. 
In  this  direction  much  has  already  been  accomplished,  but  more 
remains  to  be  done,  particularly  in  the  selection  of  a  properly 
balanced  diet  and  in  the  adaptation  of  the  diet  to  special  conditions. 
The  principles  governing  the  selection  of  a  diet  adequate  to  meet 
the  energy  needs  of  an  individual  or  group  of  individuals  are  simple, 
and  in  recent  years  they  have  been  followed  successfully  by  those 
charged  with  the  feeding  of  groups  of  people,  schools,  hospitals, 
armies,  etc.  But  the  energy  needs,  while  important  and  indeed 
essential,  are  not  the  only  object  to  be  borne  in  mind  in  selecting 
dietaries.  Outside  such  obvious  considerations  as  the  palatable- 
ness  and  digestibility  of  the  food  selected,  it  has  become  increas- 
ingly evident  from  experimental  studies  that  attention  must  be 
paid  to  the  proportions  of  the  various  foodstuffs  and,  indeed,  even 
to  the  particular  kinds  of  energy-yielding  foodstuffs  that  are 
selected.  To  use  a  current  phrase  the  diet  must  be  properly  bal- 
anced. It  is  possible  to  select  a  diet  which  yields  the  requisite 
amount  of  energy  and  yet  may  induce  a  condition  of  malnutrition. 
This  possibility  seems  to  be  illustrated  in  the  disease  known  as 
pellagra.  The  prevalent  view  in  regard  to  this  condition  seems  to 
be  that  it  is  due  to  a  maladjustment  in  the  elements  of  the  diet- 
ary, rather  than,  as  in  the  case  of  beriberi,  to  a  lack  of  some  special 
vitamine.  The  various  general  ways  in  which  a  diet  may  be  ill- 


956  NUTRITION    AND    HEAT    REGULATION. 

balanced  or  maladjusted  are  indicated  by  McCollum*  as  follows: 

1.  An  inadequate  supply  of  the  necessary  inorganic  constituents. 

2.  Inadequate  amounts  of  protein,  or  the  use  of  proteins  of  poor 
quality,  that  is  to  say,  of  proteins  not  containing  all  the  necessary 
amino-acids.    3.  A  lack  or  deficiency  in  one  or  both  of  the  acces- 
sories, fat-soluble  A  and  water-soluble  B.    4.  In  some  cases  the 
presence  of  toxic  substances  in  certain  foods,  e.  g.,  cotton-seed 
products.    It  is  obvious  that  along  these  lines  there  is  much  to  be 
learned  and  we  can  hope  to  acquire  the  necessary  knowledge  only 
through  laborious  experimental  inquiries. 

*  McCollum,  Harvey  Lecture,   "Jour.  Amer.   Med.  Assoc.,"  May  12, 
1917. 


CHAPTER  LI. 

THE  PRODUCTION  OF  HEAT  IN  THE  BODY— ITS  MEAS- 
UREMENT  AND  REGULATION— BODY  TEMPERA- 
TURE—CALORIMETRY— PHYSIOLOGICAL 
OXIDATIONS. 

It  is  customary  to  date  our  modern  ideas  of  the  origin  of 
animal  heat  from  the  time  of  Lavoisier  (1774-77).  To  the  older 
physiologists  it  was  a  most  difficult  problem.  The  animal's  body 
produces  heat  continually  and  maintains  a  temperature  higher,  as 
a  rule,  than  that  of  the  surrounding  air.  Since  oxygen  and  the 
nature  of  ordinary  combustions  were  unknown,  they  naturally 
explained  this  heat  formation  by  reference  to  causes  which  the 
science  of  the  day  had  shown  to  be  capable  of  producing  warmth, 
such  as  friction  and  fermentation.  Haller  (1757),  for  instance, 
taught  that  the  body  heat  arises  mainly  from  the  friction  of  the 
circulating  blood  and  the  movements  of  the  heart  and  blood-vessels, 
and  this  view  found  currency  in  text-books  well  iiito  the  nine- 
teenth century.  Lavoisier  first  gave  to  the  physiologist  the  con- 
ception that  the  heat  produced  in  the  body  is  due  to  a  combustion  or 
oxidation,  and  that  therein  lies  the  significance  of  our  respiration 
of  oxygen.  He  believed  himself  that  this  oxidation  takes  place  in 
the  lungs, — that  is,  the  blood  brings  to  the  lungs  a  hydrocarbon- 
ous  material  which  is  attacked  by  the  oxygen  and  burnt  with 
the  formation  of  water  and  carbon  dioxid  and  the  liberation  of 
heat.  Later  experimenters  demonstrated  that  the  heat  production 
does  not  occur  in  the  lungs,  at  least  not  exclusively,  but  over  the 
whole  of  the  body.  After  a  long  and  interesting  controversy  it  was 
also  shown  satisfactorily  that  the  oxidations  of  the  body  do  not 
occur  in  the  blood,  but  in  the  tissues  themselves.  The  oxygen  is 
transported  to  the  cells  and  there  does  its  work  of  effecting  oxi- 
dations and  giving  rise  to  heat.  This  heat  is  equalized  more  or 
less  over  the  whole  body,  chiefly  by  the  circulation  of  the  blood, 
which  absorbs  heat  from  the  warmer  organs  and  distributes  it  to 
the  cooler  ones.  The  body  temperature  is  maintained  at  a  nearly 
constant  level  by  an  intricate  adjustment  of  physiological  reflexes 
which  together  constitute  the  heat-regulating  mechanism.  Such 
in  brief  is  the  general  theory  of  our  time  regarding  heat  production 
in  the  body.  Many  of  the  problems  that  interested  the  older  pbys- 

957 


958  NUTRITION    AND    HEAT    REGULATION. 

iologists  have  been  solved  satisfactorily,  but  there  remain,  of  course, 
many  more  to  interest  this  and  succeeding  generations.  Investi- 
gations in  this  field  at  present  are  directed  mainly  to  an  effort  to 
understand  the  details  of  the  heat-regulating  apparatus,  on  the  one 
hand,  and,  on  the  other,  to  comprehend  more  satisfactorily  the 
nature  of  the  process  of  oxidation.  This  latter  problem  is  one  of 
common  interest  at  present  in  chemistry  and  in  physiology. 

The  Body  Temperature. — We  divide  animals  into  the  two 
great  classes  of  warm  blooded  and  cold  blooded,  according  as  their 
temperature  is  or  is  not  above  that  of  the  surrounding  air.  In 
this  sense,  birds  and  mammals  are  warm  blooded  and  reptiles, 
amphibia,  and  fishes  are  cold  blooded.  The  names,  however,  are 
badly  chosen.  The  difference  of  deepest  significance  between  the 
mammals  and  birds,  on  the  one  hand,  and  the  fishes,  amphibia,  and 
reptiles,  on  the  other,  is  that  in  the  former  the  body  temperature 
is,  within  wide  limits,  independent  of  the  outside  temperature;  it 
remains  practically  constant  during  winter  and  summer,  whether 
the  surrounding  air  is  hotter  or  cooler  than  the  body.  They  are, 
therefore,  constant-temperature  animals  (homoiothermous).  The 
reptiles,  amphibia,  and  fishes,  on  the  contrary,  have  a  body  tem- 
perature that  changes  with  the  environment.  On  winter  days 
their  temperature  is  low,  approximately  that  of  the  surrounding 
air  or  water,  and  in  summer  their  body  temperature  rises  to  cor- 
respond with  that  of  the  outside.  Strictly  speaking,  they  are  cold 
blooded  only  in  cold  surroundings.  This  group  may  be  designated 
as  the  changeable-temperature  animals  (poikilothermous).  The 
warm-blooded  animals  maintain  a  constant  high  body  temperature 
on  account  of  their  relatively  active  oxidations  and  the  existence 
of  a  heat-regulating  mechanism.  In  the  cold-blooded  animals  the 
oxidations  are  not  so  intense  and  a  heat-regulating  mechanism  is 
absent  or  poorly  developed.  The  hibernating  animals  form  a  group 
intermediate  in  many  ways  between  these  two  classes.  They  possess 
a  heat-regulating  apparatus  that  maintains  a  constant  body  tem- 
perature under  most  conditions,  but  breaks  down  in  very  cold 
weather;  so  that  during  the  period  of  winter  sleep  their  tem- 
perature is  but  little  above  that  of  the  surrounding  air.  In 
some  of  the  cold-blooded  animals  the  production  of  heat  during 
warm  weather  is  more  rapid  than  its  loss;  so  that  they  exhibit 
a  body  temperature  slightly  higher  than  the  surrounding  medium. 
A  hive  of  bees  in  activity  may  raise  the  temperature  within 
the  hive  through  a  number  of  degrees,  and  snakes  and  many 
reptiles  show  a  temperature  of  2°  to  8°  C.  above  that  of  the 
air.  So  also  some  reptiles  possess  a  rudimentary  means  of  pro- 
tecting their  bodies  from  too  great  a  rise  of  temperature,— -  for 
instance,  by  accelerated  breathing,  whereby  more  water  is  evap- 


BODY    TEMPERATURE.  959 

orated  from  the  lungs  and  thus  more  heat  is  lost.*  The  distinc- 
tion between  the  two  great  groups  of  animals  is  not  absolute,  but 
it  is  sufficiently  marked  to  constitute  a  striking  physiological  char- 
acteristic. 

The  temperature  of  the  human  body  is  measured  usually  by 
thermometers  placed  in  the  mouth,  in  the  axilla,  or  in  the  rectum. 
Measurements  made  in  this  way  show  that  in  general  the  tempera- 
ture in  the  interior  of  the  body  (rectal)  is  slightly  higher  than  on  the 
surface  of  the  skin.  The  average  temperature  in  the  rectum  is  37.2° 
C.  (98.96°  F.);  in  the  axilla,  36.9°  C.  (98.45°  F.);  in  the  mouth, 
36.87°  C.  (98.36°  F.).  We  may  speak  of  the  body  temperature, 
therefore,  in  the  places  in  which  it  can  be  conveniently  measured,  as 
varying  between  36.87°  C.  and  37.2°  C.  Some  of  the  internal  or- 
gans have  a  higher  temperature,  particularly  during  their  period  of 
greatest  activity.  t  The  temperature  of  man,  measured  in  the  places 
mentioned,  shows  also  a  distinct  variation  during  the  day,  a  diurnal 
rhythm.  This  daily  variation  has  been  measured  by  many  ob- 
servers, and  shows  individual  peculiarities  that  depend  largely  upon 
the  manner  of  living,  time  of  meals,  etc.  In  general  it  may  be  said 
that  the  lowest  temperature  is  shown  early  in  the  morning, — 6  to 
7  A.M.  ;  that  it  rises  slowly  during  the  day  to  reach  its  maximum 
in  the  evening,  5  to  7  P.M.  ;  and  falls  again  during  the  night.  The 
difference  between  early  morning  and  late  afternoon  or  evening 
may  amount  to  a  degree  or  more  centigrade,  and  this  fact  must  be 
borne  in  mind  by  physicians  when  observing  the  temperature  of 
patients.  Muscular  activity  and  food  appear  to  be  the  factors  that 
are  mainly  responsible  for  the  rise  in  temperature  during  the  day. 
Most  observers  state  that  when  the  habits  of  life  are  reversed  for 
some  time — that  is,  when  work  is  performed  and  meals  are  eaten 
during  the  night,  and  the  day  is  given  up  to  sleep  and  rest — the  daily 
variation  of  temperature  is  inverted  to  correspond, — that  is,  the 
highest  temperature  is  observed  in  the  early  morning  and  the  lowest 
in  the  late  afternoon.  Age  also  has  a  slight  influence.  Newly  born 
infants  and  young  children  have  a  somewhat  higher  temperature 
than  adults.  The  difference  may  amount  to  half  a  degree  or 
a  degree  centigrade, — 37.6°  C.  in  infants  as  compared  with 
36 . 6°  C.  or  37 . 1  °  C.  in  the  adult.  It  is  known,  also,  that  the  heat- 
regulating  mechanism  in  infants  and  young  children  is  not  so 
efficient  as  in  adults,  and  that  therefore  febrile  disturbances  are  more 
easily  excited  in  the  former  than  in  the  latter.  In  the  matter  of  body 
temperature,  as  in  so  many  other  characteristics,  aged  people  show 
a  tendency  to  revert  to  infantile  conditions.  Their  temperature, 
according  to  most  observers,  is  slightly  higher  than  in  middle  life. 

*  See  Langlois,  "  Journal  de  physiologic  et  de  pathol.  generate, "  1902, 
349. 


960  NUTRITION    AND    HEAT    REGULATION. 

Among  physiological  conditions  that  influence  the  body  tempera- 
ture, muscular  work  and  meals,  as  stated  above,  have  the  most  posi- 
tive effect.  Marked  muscular  activity  implies  a  great  increase  in 
the  production  of  heat  in  the  body  and  most  observers  find  that 
the  initial  result  at  least  is  a  small  rise  in  body  temperature, — a  fact 
which  indicates  that  the  heat  regulation  is  not  perfect;  the  excess 
of  heat  produced  is  not  dissipated  promptly.  This  effect  is  natu- 
rally most  noticeable  in  tropical  climates.  In  the  period  of  rest 
following  upon  work,  on  the  contrary,  the  body  temperature  may 
fall,  owing  probably  to  the  fact  that  more  heat  is  lost  through  the 
flushed  skin  than  is  produced  within  the  body.  In  this  matter  of 
the  effect  of  muscular  work  individual  variations  are  to  be  expected, 
since  the  perfection  of  the  heat-regulating  mechanisms  may  vary 
somewhat  in  different  persons.  Meals  also  cause  a  slight  rise  in 
body  temperature,  which  reaches  its  maximum  about  an  hour  and 
a  half  after  the  ingestion  of  the  food.  The  explanation  in  this  case 
also  is  to  be  found  doubtless  in  a  greater  production  of  heat,  due  to 
the  increased  metabolism  set  up  by  the  food  (specific  dynamic 
action,  see  p.  914).  The  excessive  production  of  heat  is  not 
compensated  completely  by  a  corresponding  increase  in  the 
heat  dissipated.*  It  is  sufficiently  obvious,  perhaps,  from  these 
facts  that  the  temperature  as  measured  by  the  thermometer  is  a 
balance  between  the  amount  of  heat  produced  and  the  amount  of 
heat  lost  or  dissipated.  The  thermometer  alone  gives  us  no  cer- 
tain indication  of  the  quantity  of  heat  produced  in  the  body.  A 
temperature  higher  than  normal,  fever  temperature,  may  be  due 
either  to  an  excessive  production  of  heat  or  to  a  deficient  dissipa- 
tion. To  understand  and  control  the  processes  by  which  the  body 
temperature  is  kept  normal  it  is  necessary  to  discover  a  means  for 
ascertaining  at  any  time  the  actual  quantities  of  heat  produced 
and  dissipated,  and  the  effect  upon  each  factor  of  different  normal 
and  pathological  conditions.  The  method  used  for  determining 
the  quantity  of  heat  is  designated  as  calorimetry.  It  is  necessary, 
therefore,  to  describe  the  principle  and  construction  of  calorimeters 
and  the  methods  of  calorimetry  before  attempting  to  explain  the 
mechanism  of  heat  regulation. 

Calorimetry. — A  calorimeter  is  an  instrument  for  measuring 
the  quantity  of  heat  given  off  from  a  body.  The  unit  employed  in 
these  determinations  is  the  calorie,— that  is,  the  amount  of  heat 
necessary  to  raise  1  gm.  of  water  1°  C.,or  more  accurately  the  amount 
of  heat  required  to  raise  1  gm.  of  water  from  15°  to  16°  C.  This 
unit  is  sometimes  designated  as  a  small  calorie  to  distinguish  it 
from  the  large  calorie  (C),— that  is,  the  quantity  of  heat  necessary 
to  raise  1  kgm.  of  water  1°  C.  The  large  calorie  is  equal  to  1000 

*  For  further  details  see  Richet,  "  La  chaleur  animale, "  1889 ;  and  Pem- 
brey,  "Animal  Heat,"  Schaefer's  "Text-book  of  Physiology,"  vol.  i,  1898. 


CALORIMETRY. 


961 


small  calories.  In  physiology  calorimeters  have  been  used  for  two 
main  purposes:  to  determine  the  heat  equivalent  of  foods, — that  is, 
the  amount  of  heat  given  off  when  the  various  foodstuffs  are  burned, 
— and,  secondly,  to  determine  the  heat  produced  and  the  heat  dissi- 
pated by  living  animals  during  a  given  period.  For  the  first  pur- 
pose the  apparatus  that  is  most  frequently  employed  at  present  is 
the  bomb  calorimeter  devised  by  Berthelot.  The  bomb  consists 
of  a  strong  steel  cylinder  in  which  the  food  to  be  burned  is  placed 


CT 


Fig.   300. — Reichert's  water  calorimeter. 


and  which  is  filled  with  oxygen.  The  combustion  of  the  foodstuff 
is  initiated  by  means  of  a  spiral  of  platinum  wire  heated  by  an 
electrical  current.  The  bomb  is  immersed  in  water  and  the  heat 
given  off  raises  the  temperature  of  the  water  a  certain  number 
of  degrees  centigrade.  The  weight  of  water  being  known,  the 
amount  of  heat  is  easily  expressed  in  calories.  For  the  purpose 
of  measuring  the  heat  given  off  by  living  animals  two  principal 
forms  of  calorimeter  are  used,  each  form  having  a  number  of 
modifications.  These  two  forms  are  the  water  calorimeter  and  the 
air  calorimeter;  The  water  calorimeter  was  the  form  used  in  the 
first  experiments  on  record  (Crawford,  1779).  In  principle  it 
consists  of  a  double-walled  box  with  a  known  weight  of  water 
between  the  walls.  The  animal  is  placed  in  the  inner  box  and  the 
61 


962  NUTRITION    AND    HEAT    REGULATION. 

heat  given  off  is  absorbed  by  the  water.  Knowing  the  weight  of 
the  water  and  how  much  its  temperature  is  raised,  the  data  are  at 
hand  for  determining  the  number  of  calories  given  off  during  the 
experiment.  One  form  of  this  variety  of  calorimeter,  used  in  this 
country  by  Reichert,  is  shown  in  Fig.  300.  It  consists  of  two  con- 
centric boxes  of  metal  with  the  space  between  them  filled  with 
water.  The  animal  is  placed  in  the  inner  box  (A).  The  two 
boxes  are  inclosed  in  a  large  wooden  box,  the  space  between 
the  metal  and  wooden  boxes  being  filled  with  shavings  (SH). 
The  object  of  this  outer  box  is  to  prevent  radiation  of  heat  from 
the  metal  boxes.  The  tubes  EN  and  EX,  which  lead  into  the 
interior  chamber  containing  the  animal,  are  for  the  entrance 
and  exit  of  the  ventilating  air.  A  thermometer  is  placed  in 
each  to  determine  the  heat  carried  off  by  the  air.  The  ther- 
mometer, CT,  measures  the  temperature  of  the  water,  and  S  is 
a  stirrer  to  keep  the  water  well  mixed  and  thus  insure  a  uniform 
temperature.  When  the  animal  is  placed  in  the  apparatus  the 
heat  given  off  warms  not  only  the  water,  but  also  the  metal ;  so 
that  to  determine  the  total  heat  the  weight  of  metal  must  be  re- 
duced to  an  equivalent  amount  of  water  by  multiplying  its  weight 
by  its  specific  heat,  or,  a  more  simple  method,  the  calorimetric  equiv- 
alent of  the  apparatus  is  determined, — that  is,  the  actual  amount  of 
heat  necessary  to  raise  the  temperature  of  the  apparatus,  water  and 
metal,  one  degree.  This  value  is  obtained  by  burning  in  the  appa- 
ratus a  known  weight  of  some  substance  (alcohol,  hydrogen)  whose 
heat  of  combustion  is  known.  Knowing  how  much  heat  is  given 
off  by  this  combustion  and  how  much  the  temperature  of  the 
apparatus  is  raised,  the  calorimetric  equivalent  is  easily  calcu- 
lated and  may  be  used  subsequently  in  estimating  the  results  ob- 
tained from  animals.  In  the  use  of  the  apparatus  many  precau- 
tions must  be  observed.  These  practical  details  need  not  be  des- 
cribed here  except  to  say  that  account  must  be  taken  of  the  warm- 
ing of  the  air  used  to  ventilate  the  apparatus  and  of  any  changes 
in  the  amount  of  its  moisture.  The  calorimeter  used  in  this  way 
measures  directly  the  amount  of  heat  given  off  from  the  animal 
during  the  period  of  observation.  The  amount  of  heat  produced  in 
the  animal's  body  during  this  time  may  be  the  same,  or  may  be 
more  or  less.  To  arrive  at  a  knowledge  of  this  factor  observations 
must  be  made  upon  the  animal's  body  temperature  by  means  of  a 
thermometer  in  the  rectum.  If  this  body  temperature  is  the  same 
at  the  end  as  at  the  beginning  of  the  experiment  then  it  is  obvious 
that  the  heat  produced  must  have  been  equal  to  the  heat  lost.  If 
the  animal's  body  temperature  has  fallen,  then  it  is  evident  that 
less  heat  has  been  produced  than  was  lost.  To  ascertain  how  much 
less,  the  weight  of  the  animal  is  multiplied  by  its  specific  heat  (0 . 8) 


CALORIMETRY.  963 

to  reduce  it  to  so  much  water,  and  this  product  is  multiplied  by  the 
difference  in  body  temperature  at  the  beginning  and  the  end  of  the 
experiment.  The  product  is  obtained  in  calories  and  is  subtracted 
from  the  amount  of  heat  lost,  as  determined  by  the  calorimeter,  to 
obtain  the  amount  of  heat  produced.  If,  on  the  contrary,  the  ani- 
mal's temperature  has  risen  during  the  experiment  the  body  has 
produced  more  heat  than  it  has  dissipated.  The  increase  may  be 
determined  as  above  by  multiplying  the  weight  of  the  animal,  the 
specific  heat  of  the  body,  and  the  difference  in  temperature.  This 
amount  added  to  the  heat  lost  gives  the  heat  produced. 

Many  investigators  have  used  some  form  of  air  calorimeter. 
An  air  calorimeter  consists  essentially  of  a  double-walled  chamber 
or  box  with  air  between  the  walls.  The  animal  is  placed  in  the 
inner  box  and  the  heat  given  off  is  measured  by  the  expansion  of 
the  air  between  the  walls.  Many  different  forms  are  used,  prefer- 
ence being  given  to  some  modification  of  the  differential  air  calor- 
imeter. In  this  last-named  instrument  two  exactly  similar  cham- 
bers are  constructed;  one  contains  the  animal,  while  the  other  serves 
as  a  dummy.  These  two  chambers  are  balanced  against  each  other, 
the  air  space  in  the  dummy  being  heated  by  immersion  in  a  bath  or 
by  burning  hydrogen  in  the  interior.  As  these  sources  of  heat  are 
known  and  can  be  controlled,  it  is  evident  that  if  the  dummy  is 
made  to  balance  exactly  the  chamber  containing  the  animal  the 
amount  of  heat  given  off  in  each  is  the  same.* 

The  Respiration  Calorimeter. — When  a  calorimeter  is  so  arranged 
that  the  composition  of  the  air  drawn  through  the  apparatus  for 
ventilation  can  be  determined,  as  well  as  the  amount  of  heat  pro- 
duced, the  apparatus  becomes  a  respiration  calorimeter.  In  such 
an  apparatus,  if  proper  provision  is  made  for  analyzing  the  urine, 
the  feces,  and  the  food,  the  total  carbon  and  nitrogen  excretion  may 
be  obtained  simultaneously  with  the  heat  loss.  Since  we  may 
calculate  from  the  carbon  and  nitrogen  excretion  how  much  pro- 
tein, fat,  and  carbohydrate  have  been  burnt  in  the  body,  and  since 
the  heat  values  of  these  constituents  are  known,  it  is  evident  that 
we  may  reckon  indirectly  how  much  heat  ought  to  be  produced 
from  the  combustion  of  so  much  material.  This  method  of  arriv- 
ing at  the  heat  production  is  designated  indirect  calorimetry.  With 
an  adequate  respiration  calorimeter  it  is  possible  to  ascertain 
whether  the  results  calculated  by  the  method  of  indirect  calorim- 
etry really  correspond  with  the  heat  obtained  by  direct  measure- 
ment. In  the  hands  of  good  observers  the  correspondence  is 
very  close,  and  gives  substantial  proof  of  the  scientific  belief 

*  For  detailed  accounts  of  special  forms  of  air  calorimeters  see  Rubner, 
"Calorimetrische  Methodik,"  1891;  and  Rosenthal,  "Archiv  f.  Physiologie," 
1897,  p.  170. 


964 


NUTRITION    AND    HEAT   REGULATION. 


that  in  the  living  body  the  energy  liberated  as  heat  or  as  heat 
and  work  is  all  contained  in  potential  form  in  the  foodstuffs 
eaten.  By  means  of  the  respiration  calorimeter  we  can  obtain  a 
balance  between  the  energy  income  and  outgo  of  the  body  as  well 
as  between  the  material  income  and  outgo, — that  is,  the  carbon  and 
nitrogen  equilibrium.  The  most  complete  and  elaborate  form  of 
respiration  calorimeter  used  is  that  devised  by  Atwater  and  Rosa 
for  experiments  upon  man.*  The  respiration  chamber  is  a  small 
room  lighted  and  furnished  so  that  an  individual  may  remain  in 
it  for  long  periods  without  discomfort.  As  shown  in  Fig.  301,  this 


Fig.  301. — Horizontal  section  of  respiration  calorimeter.  Portions  shaded  are  of  wood:  A,- 
dead-air  space  between  Cu  and  Zn  walls;  B,  dead-air  space  between  Zn  wall  and  inside  wooden 
wall;  C,  dead-air  space  between  inside  and  outside  wooden  walls;  D,  pneumatic-packing  air 
and 'heat  insulated;  E,  food-aperture  tube;  a,  a,  airtight  ports  (glass);  H,  ingoing  water  for 
absorbing  heat;  G,  outcoming  water;  V,  ventilating  air  current.  (Atwater  and  Benedict.) 

room  is  arranged  as  a  calorimeter.  It  has  several  walls  of  metal 
and  wood  to  prevent  loss  of  heat  to  the  outside  or  the  reverse,  and 
by  means  of  water  circulating  through  a  system  of  pipes  within 
the  room  the  heat  given  up  by  the  body  is  carried  off.  By  regulat- 
ing this  flow  of  water  the  temperature  of  the  chamber  can  be  kept 
constant.  Knowing  the  temperature  of  the  water  as  it  enters  and 
leaves  the  chamber  and  the  volume  of  the  flow,  the  heat  production 
of  the  individual  may  be  calculated  in  terms  of  calories.  For  the 
determination  of  the  carbon  dioxid  and  water  air  is  drawn  through 
the  room  by  means  of  a  rotary  pump  and  a  closed  circuit  is  em- 
ployed, that  is  to  say,  the  same  air  is  kept  circulating  through  the 

*  See  Atwater  and  Rosa,  Bulletin  63,  United  States  Department  of  Agri- 
culture, 1899;  and  for  recent  improvements,  Atwater  and  Benedict,  "A  Respi- 
ration Calorimeter,"  Carnegie  Institution,  Washington,  1905. 


RESULTS    OF    CALORIMETRIC    MEASUREMENTS. 


965 


room,  but  provision  is  made  for  absorbing  the  C02  and  water  as 
it  is  formed,  and  for  adding  new  oxygen  from  an  oxygen  tank  as  it 
is  needed.  This  arrangement  is  represented  schematically  in 
Fig.  301a.  It  is  possible  in  this  form  of  calorimeter  to  determine 
the  amount  of  oxygen  consumed  as  well  as  the  amount  of  carbon 
dioxid  eliminated.  By  this  means  the  observer  can  ascertain  the 

respiratory  coefficient   (-7^),  a  factor  of  much  value,   since   it 

\   \J2  I 

throws  light  on  the  nature  of  the  material  undergoing  oxidation 
in  the  body.  By  means  of  this  apparatus  many  interesting  and 
important  experiments  have  been  made  upon  the  nutrition  of 
man  under  different  physiological  and  pathological  conditions, 
and  it  seems  probable  that  it  will  supplant  entirely  the  earlier 
forms  of  calorimeter  described  in  the  preceding  pages.  As  an 
indication  of  its  sensitiveness  the  following  result  may  be  quoted 


RESPIRATION  CHAMBER 
0  used 

Hi°\  produced 


,    n-    .        . 

O  deficient 


Fig.  301o. — Diagram  of  circulation  of  air  through  respiration  apparatus.   (Atwater  and  Benedict.) 

from  observations  made  upon  a  man  who,  while  in  the  apparatus, 
did  much  muscular  work  on  a  bicycle  ergometer: 

Income :  Potential  energy  of  material  metabolized  in  body   «=    5459  CaL 

f  Energy  given  off  from  the  body  as  heat ....  4833  Cal. 
uutgo    ^  Heat  equivalent  of  muscular  work 602  Cal. 

5435  Cal.          5435  CaL 
Experimental  error 24  CaL 

Results  of  Calorimetric  Measurements. — The  actual  results 
obtained  from  direct  calorimetric  measurements  corroborate  those 


966 


NUTRITION    AND    HEAT    REGULATION. 


deduced  from  the  study  of  the  energy  given  off  in  the  oxidation  of 
the  foodstuffs  of  the  daily  diet.  They  show  that  the  adult  when  fast- 
ing (basal  metabolism)  gives  off  heat  from  his  body  to  the  amount  of 
about  24  Calories  per  kilogram  of  weight  during  twenty-four  hours, 
that  is,  about  1  Calorie  per  hour  per  kilogram  of  body  weight,*  or, 
expressed  in  another  unit,  about  40  Calories  per  hour  per  square 
meter  of  skin  surface.  This  amount  is  increased  greatly  under 
conditions  demanding  much  muscular  work.  This  loss  of  heat  is, 
of  course,  made  good  by  the  production  of  an  equal  amount  within 
the  body  by  the  oxidation  of  the  food  material,  f  Actual  experi- 
ments upon  different  animals  show  that  small  animals  produce  more 


CAL 


YRS.       10 


Fig.  3016. — Du  Bois's  figure  to  show  the  variation  of  basal  metabolism  with  age.     The 
results  are  expressed  in  terms  of  calories  per  square  meter  of  body  surface  per  hour;  the  age  is 

f'ven  along  the  abscissa  and  the  calories  per  square  meter  per  hour  along  the  ordinates. — (From 
.F.  Du  Bois,  "American  Journal  of  the  Med.  Sciences,"  June,  1916.) 

heat  in  proportion  to  their  weight  than  larger  animals  of  the  same 
species,  owing  to  their  relatively  larger  surface,  and,  therefore, 
greater  loss  of  heat.  This  fact  has  been  expressed  by  Rubner  in 
what  he  calls  his  surface  area  law.  According  to  this  law  the  metab- 
olism is  proportional  to  the  surface  area,  or  for  the  same  amount 
of  surface  area  there  will  be  the  same  production  of  heat.  He  esti- 
mates that  in  man  there  is  produced  in  twenty-four  hours  for  each 
square  meter  of  surface  1042  Calories.  This  important  generaliza- 
tion has  been  investigated  with  care  by  E.  F.  and  D.  Du  Bois.J 


*  Du  Bois  and  Gephart  and  Du  Bois,  "Archives  of  Internal  Medicine," 
17,  887,  902,  1916;  Benedict,  et.  al.,  "Journal  of  Biological  Chemistry,"  18, 
139,  1914. 

fSee  Rubner,  "Zeitschrift  f.  Biologie,"  19,  535,  1883;  and  "Gesetze  des 
Energieverbrauchs,"  1902. 

t  Du  Bois,  D.  and  E.  F.,  "Archives  of  Internal  Medicine,"  15,  868, 1915, 
and  17,  863,  1916. 


RESULTS    OF    CALORIMETRIC    MEASUREMENTS.  967 

They  have  devised  a  simple  formula  for  estimating  the  surface 
area  in  terms  of  the  height  and  weight  of  the  individual. 

A  =  W<>-425  x  HO-725  x  71.84 

Making  use  of  this  formula,  whose  average  error  is  about 
1.7  per  cent.,  they  find  that  in  adult]  life  the  basal  metabol- 
ism of  different  individuals  shows  a  quite  constant  relationship 
to  the  surface  area.  As  stated  above,  the  average  figure  indi- 
cates a  heat  production  of  40  Calories  per  hour  per  square 
meter  of  surface.  With  advancing  age  there  is  a  slight  falling 
off  in  metabolism,  while  in  infancy  and  childhood  there  is  a 
notable  increase.  The  relationship  as  pictured  by  these  observ- 
ers is  illustrated  in  the  accompanying  chart  (Fig.  3016). 

HEAT  REGULATION. 

From  a  general  standpoint  the  most  important  problem  that  the 
physiologist  has  to  study  is  the  means  by  which  the  heat  production 
and  heat  loss  are  so  regulated  as  to  maintain  a  practically  constant 
body  temperature.  Experiments  show  that  the  mechanism  of 
heat  regulation  is  very  complex  and  is  two-sided, — that  is,  the  body 
possesses  means  of  controlling  the  loss  of  heat  as  well  as  the  produc- 
tion of  heat,  and  under  the  conditions  of  normal  life  both  means 
are  used. 

Regulation  of  the  Heat  Loss. — Heat  is  regularly  lost  from  our 
bodies  in  a  number  of  different  ways,  which  may  be  classified  as 
follows : 

1.  Through  the  excreta,  urine,  feces,  saliva,  which  are  at  the  temperature 

of  the  body  when  voided. 

2.  Through  the  expired  air.     This  air  is  warmer  than  the  inspired  air, 

and,  moreover,  is  nearly  saturated  with  water-vapor.  The  vaporiza- 
tion of  water  requires  heat,  which  is,  of  course,  taken  from  the  body 
supply.  Each  gram  of  water  requires  for  its  vaporization  about  0.5  cal. 

3.  By  evaporation  of  the  sweat  from  the  skin.     The  amount  lost  in  this 

way  increases  naturally  with  the  amount  of  sweat  secreted. 

4.  By  conduction  and  especially  by  radiation  of  heat  from  the  skin. 

The  relative  values  of  these  different  means  of  heat  loss  are 
estimated  as  follows  by  Vierordt: 

1.  By  urine  and  feces 1.8  per  cent,  or        48  calories. 

2.  By  expired  air:  Warming  of  air 3.5  84 

Vaporization  of  water  from  lungs. .......   7.2  182 

3.  By  evaporation  from  skin 14.5  364 

4.  By  radiation  and  conduction  from  skin. . . .  73.0  1792 

Total  daily  loss  =  2470 

It  is  obvious  that  the  relative  importance  of  these  factors  will  vary 


968 


NUTRITION    AND    HEAT   REGULATION. 


with  conditions.  Thus,  high  external  temperatures  will  tend  to 
diminish  the  loss  from  radiation  while  increasing  that  from  evapora- 
tion, owing  to  the  greater  production  of  sweat.  The  variation 
in  this  respect  is  well  illustrated  by  the  following  table,  compiled 
by  Rubner,  from  experiments  made  upon  a  starving  dog:* 


Temperature. 

Calories  lost  by  radia- 
tion and  conduction. 

Calories  lost  by 
evaporation. 

Total  calories  of 
metabolism. 

7°  C. 

78.5 

7.9 

86.4 

15° 

55.3 

7.7 

63.0 

20° 

45.3 

10.6 

55.9 

25° 

41.0 

13.2 

54.2 

30° 

33.2 

23.0 

56.2 

It  will  be  noted  that  between  25°  and  30°  C.  there  was  a  marked 
increase  in  the  loss  of  heat  through  evaporation. 

In  man  loss  of  heat  is  regulated  chiefly  by  controlling  the  impor- 
tant factors  of  evaporation  and  radiation.  We  accomplish  this  end  in 
part  deliberately  or  voluntarily  by  the  use  of  appropriate  clothing. 
Clothing  of  any  kind  captures  a  layer  of  warm  and  moist  air  between 
it  and  the  skin  and  thus  diminishes  greatly  the  loss  by  evaporation 
and  by  radiation.  In  cold  weather  the  amount  and  character  of  the 
clothing  is  changed  in  order  to  diminish  the  heat  loss.  The  ideal 
clothing  for  this  purpose  is  made  of  material,  such  as  wool,  which, 
while  porous  enough  to  permit  adequate  ventilation  of  the  air  next 
to  the  skin,  is  at  the  same  time  a  popr  conductor  of  heat  and  thus 
diminishes  the  main  factor  of  loss  by  radiation.  The  most  impor- 
tant means  of  controlling  the  heat  loss,  however,  is  by  automatic 
reflex  control  through  the  sweat  nerves  and  the  vasomotor  nerves. 
By  these  means  the  amount  of  perspiration  evaporated  from  the 
skin  and  the  amount  of  warm  blood  sent  through  the  skin  are 
controlled.  Rubner  speaks  of  this  side  of  the  heat  regulation 
as  the  physical  regulation.  By  its  means  the  body  may  be  safe- 
guarded from  an  abnormal  rise  of  temperature.  In  warm  weather 
the  secretion  of  sweat  is  greatly  increased  by  reflex  stimulation 
of  the  sweat  nerves.  The  greater  amount  of  water  requires  a 
greater  amount  of  heat  to  vaporize  it,  and  thus  the  heat  loss 
is  increased.  The  value  of  this  control  is  illustrated  by  a  case 
recorded  by  Zuntz  f  of  a  man  who  possessed  no  sweat  glands.  In 
summer  this  individual  was  incapacitated  for  work,  since  even  a 
small  degree  of  muscular  activity  would  cause  an  increase  in  his 
body  temperature  to  40°  or  41°  C. 

*  Taken  from  Lusk,  "Elements  of  the  Science  of  Nutrition,"  Philadelphia, 
1917. 

t  Zuntz,  "Deutsch  medizinal-Zeitung,"  1903,  No.  25. 


REGULATION  OF  HEAT  PRODUCTION.  969 

The  control  through  the  vasomotor  nerves  is  doubtless  even 
more  important.  The  blood-vessels  bring  the  warm  blood  to  the 
skin,  where  it  loses  its  heat  by  conduction  and  especially  by  radia- 
tion to  the  cooler  air.  When  the  surrounding  air  is  much  below  the 
temperature  of  the  body  the  vasoconstrictor  center  is  stimulated, 
the  blood-vessels  in  the  skin  are  constricted,  the  supply  of  warm 
blood  to  the  skin  is  diminished,  and  therefore  the  amount  of  heat  lost 
is  less.  The  reflex  in  this  case  may  be  attributed  primarily  to  the 
action  of  the  cool  air  on  the  cold  nerves  of  the  skin.  The  impulses 
carried  by  these  fibers  to  the  nerve  centers  stimulate  the  vasocon- 
strictor center  or  that  part  of  it  controlling  the  vasomotor  fibers 
to  the  skin.  On  warm  days,  on  the  contrary,  the  blood-vessels 
in  the  skin  are  dilated  sometimes  to  an  extreme  extent,  the 
supply  of  warm  blood  is  therefore  increased,  and  more  heat 
is  lost  if  the  air  is  lower  in  temperature  than  the  blood.  The 
reflex  in  this  case  may  be  regarded  possibly  as  an  inhibition  of  the 
vasoconstrictor  center  through  the  warm  nerves  of  the  skin.  Sub- 
stances, such  as  alcohol,  which  cause  a  dilatation  of  the  skin  ves- 
sels also  increase  the  loss  of  body  heat,  in  some  cases  to  a  sufficient 
extent  to  lower  the  body  temperature.  To  a  smaller  extent  our 
heat  loss  is  controlled  through  an  acceleration  of  the  breathing 
movements.  The  greatly  increased  respirations  in  muscular  ac- 
tivity must  aid  somewhat  in  eliminating  the  excess  of  heat  produced, 
although  this  factor  must  be  much  less  important  than  the  sweating 
and  the  flushing  of  the  skin  which  are  produced  reflexly  during 
muscular  work.  In  some  of  the  lower  animals — the  dog,  for  in- 
stance— in  which  the  sweat  nerves  are  absent  over  most  of  the  body 
and  in  which  the  coat  of  hair  interferes  with  the  free  loss  by 
radiation,  it  is  found  that  the  loss  through  the  respiratory  channel  is 
relatively  more  important.  The  panting  of  the  dog  is  a  familiar 
phenomenon.  Richet  has  studied  this  reflex  upon  dogs  and  has 
designated  the  greatly  accelerated  breathing  in  warm  weather  or 
after  muscular  exercise  as  thermic  polypnea  (according  to  Gad, 
tachypnea).  He  assumes  a  special  center  for  the  reflex  situated  in 
the  medulla  and  acting  through  the  respiratory  center.  It  is  a 
curious  fact,  as  shown  by  Langlois,  that  some  reptiles  exhibit  a 
similar  reflex;  when  their  body  temperature  is  raised  to  39°  C.  they 
show  a  condition  of  marked  polypnea  (rapid  breathing)  the  ap- 
parent object  of  which  is  to  augment  the  loss  of  heat  from  the 
body. 

Regulation  of  Heat  Production. — Heat  production  is  varied 
in  the  body  by  increasing  or  decreasing  the  physiological  oxida- 
tions. This  end  is  effected  in  part  voluntarily  by  muscular  exercise 
or  by  taking  food.  Muscular  contractions  are  attended  by  a 
marked  liberation  of  heat  and  it  is  a  part  of  everyone's  experience 


970 


NUTRITION    AND    HEAT    REGULATION. 


that  by  work  or  muscular  activity  the  effect  of  outside  cold  may  be 
counteracted.  During  fasting  a  certain  amount  of  body  material 
(glycogen,  fat,  protein)  is  oxidized  and  sufficient  heat  is  produced 
to  counterbalance  the  heat  that  is  lost.  If  food  is  taken  it  will  be 
oxidized,  and  the  supply  of  body  material  will  be  spared.  But 
the  digested  products  of  the  foodstuffs,  especially  of  the  proteins, 
stimulate  the  body  metabolisms  (specific  dynamic  action,  p.  914), 
and  cause  an  increase  in  heat  production.  By  this  means,  there- 
fore, the  quantity  of  heat  formed  in  the  body  may  be  raised  tem- 
porarily above  the  usual  level.  Outside  cold  is  most  effective 
in  stimulating  the  appetite  and  thus  leading  us  to  increase  the 
diet.  In  this,  as  in  other  respects,  the  appetite  serves  to  control 
the  amount  of  food  in  proportion  to  the  needs  of  the  body.  '  The 
purely  involuntary  control  of  heat  production  consists  of  an 
involuntary  reflex  upon  muscular  metabolism  and  possibly  in 
the  existence  of  a  special  set  of  heat  centers  and  heat  nerves. 
With  regard  to  the  first  effect  we  have  the  striking  experiments 
quoted  by  Pfliiger,*  according  to  which  a  rabbit  paralyzed  by  large 
doses  of  curare  is  no  longer  able  to  maintain  its  body  temper- 
ature when  the  outside  temperature  is  changed.  The  rabbit 
behaves,  in  fact,  like  a  cold-blooded  animal.  In  the  calorimeter 
it  shows  a  marked  loss  of  heat  production,  and  its  temperature 
may  be  made  to  go  up  and  down  with  the  outside  temperature. 
The  same  result  may  be  obtained  by  section  of  all  the  motor 
nerves, — that  is,  section  of  the  spinal  cord  in  the  upper  cervical 
region.  Rubner  has  shown  by  calorimetric  experiments  upon 
animals  that  although  the  body  temperature,  as  we  know,  may 
remain  constant  when  the  outside  temperature  is  changed,  the 
heat  production  is  increased  as  the  outside  temperature  is  low- 
ered. This  fact  is  well  shown  by  the  following  table,  compiled 
by  Rubner,  from  experiments  made  upon  a  fasting  guinea-pig  :f 


Temperature 
of  air. 

Temperature 
of  animal. 

Grams  of  CO2  eliminated  per  hour 
and  per  kilogram  of  animal. 

0.0°  C. 

37.0°  C. 

2.905 

11.1 

37.2 

2.151 

20.8 

37.4 

.766 

25.7 

37.0 

.540 

30.3 

37.7 

.317 

34.9 

38.2 

.273 

40.0 

39.5 

.454 

From  0°  to  about  35°  C.  the  animal's  body  temperature  remained 
practically  constant,  but  the  oxidations  at  the  lower  temperature 

*  Pfliiger,  "Archiv  f.  die  gesammte  Physiologic,"  18,  255,  1878. 
t  Taken  from  Lusk,  loc.  cit. 


EXISTENCE    OF    HEAT    CENTERS    AND    HEAT    NERVES.  971 

were  en  er  twice  the  amount  of  those  at  the  higher  temperature. 
At  about  33°  C.  the  metabolism  of  the  mammal,  according  to 
Rubner,  is  at  its  minimum.  From  35°  to  40°  C.  the  heat  regula- 
ting mechanism  in  the  experiments  quoted  broke  down,  in  that 
heat  loss  was  prevented  to  such  an  extent  by  the  outside  high 
temperature  that  the  body  temperature  rose  in  spite  of  the 
diminution  in  heat  production.  The  increased  production  of 
heat  in  the  body  in  consequence  of  a  fall  in  external  temperature 
is  a  characteristic  property  of  warm-blooded  animals.  Rubner 
designates  this  side  of  the  regulating  mechanism  as ''the  chemical 
regulation,  and  he  calls  attention,  moreover,  to  the  fact  that  in 
mankind,  owing  to  our  custom  of  protecting  the  surface  of  the 
body  by  clothing  and  by  artificial  heat,  chemical  regulation 
plays  less  of  a  role  than  in  the  lower  animals.  Man,  in  fact, 
keeps  most  of  his  skin  surrounded  by  a  warm  layer  of  air  at 
about  the  temperature  (33°  C.)  at  which  the  metabolism,  as 
affected  by  temperature,  is  minimal.  Cold  baths,  cold  winds, 
and  various  climatic  conditions,  such  as  high  altitudes  and  sea- 
side conditions,  may  cause  a  marked  increase  in  body  metabolism. 
Johannson*  has  shown  that  the  increased  oxidations  that  occur 
under  the  influence  of  outside  cold,  as  measured  by  the  CO2  out- 
put, occur  only  when  muscular  tension  is  increased  or  shivering 
is  noticed.  We  may  believe,  therefore,  that  the  increased  oxida- 
tions caused  by  cold  are  due  to  motor  reflexes  upon  the  skeletal 
muscles.  These  reflexes  take  place  doubtless  through  the  motor 
fibers,  and  lead  to  an  augmented  muscular  tone  or  to  small  con- 
tractions (shivering),  according  to  their  intensity.  This  fact 
accords  with  one's  personal  sensations  regarding  the  condition  of 
his  muscles  in  cold  weather. 

The  Existence  of  Heat  Centers  and  Heat  Nerves. — Physi- 
ologists have  long  supposed  that  there  may  be  in  the  body  a  special 
set  of  heat  nerves  and  heat  centers,  separate  in  their  action  from  the 
motor,  secretory,  and  other  efferent  nerves  that  influence  the  me- 
tabolism of  the  peripheral  organs.  It  is  supposed  that  these  fibers, 
if  they  exist,  when  in  activity  augment  or  inhibit  the  physiological 
oxidations  in  the  tissues,  and  that  this  effect  has  for  its  specific 
object  an  increase  or  decrease  in  heat  production,  outside  of  any 
functional  activity  of  the  tissues.  Bernard  thought  at  first  that 
he  had  demonstrated  the  existence  of  calorific  fibers  in  the  cervical 
sympathetic,  but  it  was  afterward  recognized  that  the  fibers  in 
question  are  vasoconstrictors.  Since  that  time  very  numerous 
experiments  have  been  made  with  this  object  in  view,  but  it  must 
be  admitted  that  no  conclusive  proof  has  yet  been  obtained  of  the 
existence  of  such  a  system.  The  evidence  that  has  been  most  re- 
*  Johannson,  "Skandinavisches  Archiv.  f.  Pysiologie,"  7,  123,  1897. 


972  NUTRITION    AND    HEAT   REGULATION. 

lied  upon  is  the  effect  of  lesions,  experimental  or  pathological,  of 
definite  portions  of  the  brain  or  cord.  An  important  fact,  brought 
out  by  Ott,*  is  that  injury  to  the  corpus  striatum  causes  a  rise  in 
heat  production  and  body  temperature.  This  result  has  been  con- 
firmed by  many  other  investigators,  making  use  especially  of  what 
is  known  as  the  "heat  puncture."  In  this  experiment,  made  upon 
rabbits,  a  probe  or  style  is  inserted  into  the  brain  so  as  to  puncture 
the  corpus  striatum.  The  result  in  the  majority  of  cases  is  a  rise 
of  temperature  together  with  an  increase  in  heat  production  which 
may  last  for  a  long  time,  although  the  animal  shows  no  paralysis 
and  apparently  no  other  effect  from  the  operation.  White  and 
others  have  described  similar  disturbances  of  heat  production  from 
lesions  of  the  optic  thalamus.  Heat  centers  have  been  located  also 
in  the  septum  lucidum,  in  the  cortex,  the  midbrain,  pons,  and  med- 
ulla. Barbourf  has  shown  that  when  by  a  special  device  the  corpus 
striatum  is  heated  locally  to  42°  C.  or  higher  there  follows  a  fall  in 
body  temperature,  while,  on  the  contrary,  cooling  of  the  region  of 
the  corpus  striatum  to  33°  C.  or  lower  causes  a  rise  in  body  temper- 
ature. The  implication  from  these  experiments  is  that  there  exists 
in  the  corpus  striatum  a  heat-regulating  center  whose  action  is 
controlled  by  temperature  changes  in  the  brain  itself,  a  rise  of 
brain  temperature  depressing  the  activity  of  the  center  and  leading 
to  a  lowering  of  body  temperature,  while  a  fall  in  brain  temperature 
has  the  opposite  effect.  The  author  finds  that  similar  reactions 
may  be  obtained  by  the  local  application  of  various  substances, 
caffein,  for  example,  causing  a  rise  of  body  temperature,  while 
chloral,  antipyrin,  quinin,  etc.,  cause  a  fall.  The  effect  of  the 
action  of  such  a  center  may  be  pictured  as  causing  the  balance 
between  heat  production  and  heat  loss  to  be  set  at  a  different  level, 
higher  or  lower  than  the  normal,  and  the  same  conception  may  be 
employed  in  explaining  the  rise  of  temperature  in  fevers  or  in  heat- 
stroke, t  So-called  septic  fevers  are  due  probably  to  the  action  of 
some  of  the  cleavage  products  of  protein  formed  as  the  result  of 
bacterial  growth.  We  might  assume  that  these  toxic  products 
affect  directly  the  heat-regulating  center,  and  through  it  cause  the 
balance  to  be  set  at  a  higher  level,  with  an  increase  in  both  heat 
production  and  heat  dissipation.  Aseptic  fevers  or  reactions  can 
be  produced  also  by  conditions  that  cause  the  disintegration  of 
tissue  elements,  hemolysis,  for  example.  The  effect  in  this  case 
also  may  be  due  to  the  action  of  some  of  the  split  products  of  pro- 

*  Ott,  "Journal  of  Nervous  and  Mental  Diseases,"  1884,  1887,  1888;  also 
"Fever,  Its  Thermqtaxis  and  Metabolism,"  1914. 

t  Barbour,  "British  Medical  Journal/'  September  13,  1913;  also  "Journal 
of  Pharmacology  and  Exp.  Therapeutics,"  5,  105,  1913. 

J  Consult  Krehl,  "Pathological  Physiology."  Translation  by  Beifeld, 
1916. 


PHYSIOLOGICAL    OXIDATIONS.  973 

tein  on  the  heat-regulating  center.  In  heat-stroke  there  is  also  a 
rise  of  body  temperature  due  directly  apparently  to  prolonged 
exposure  to  high  outside  temperature.  Here  the  normal  regula- 
tion again  breaks  down,  but  since  the  rise  of  body  temperature  may 
persist  for  a  long  time  after  the  initial  cause  is  removed,  it  may  be 
explained  by  assuming  that  the  heat-regulating  center  has  been 
injured,  so  that  it  is  unable  to  exercise  its  normal  control  of  the 
balance  between  heat  production  and  heat  loss.  Granting  the 
existence  of  such  a  regulating  center  in  the  corpus  striatum,  with 
possibly  accessory  connections  to  other  basal  ganglia  of  the  brain, 
there  remains  the  question  as  to  whether  this  center  acts  upon  the 
heat  production  and  dissipation  through  a  special  set  of  calorific 
nerve-fibers,  or  whether  its  influence  is  exerted  more  indirectly 
through  the  nervous  mechanisms  which,  as  we  have  seen  above, 
have  been  utilized  to  explain  the  phenomena  of  so-called  physical 
and  chemical  regulation.  At  present  it  may  be  said  with  confidence 
that  no  convincing  evidence  has  been  furnished  for  the  existence  of 
a  special  group  of  calorific  nerve-fibers.  Most  physiologists  prob- 
ably are  inclined  to  believe  that  the  variations  in  heat  production 
and  heat  dissipation  are  controlled  through  excitation  or  inhibition 
of  the  recognized  mechanisms,  which  may  be  tabulated  as  follows: 


Heat  loss 
physical  regulation 

Heat  production 
chemical  regulation 


1.  The  sweat  centers  and  sweat  nerves. 

2.  The  vasomotor  center  and  vasomotor  nerves. 

3.  The  respiratory  center. 

1.  The  motor  nerve  centers  and  the  motor  fibers  to  the 

muscles. 

2.  The  stimulating  action  of  food  on  metabolism. 


But  it  may  well  be  that  the  activity  of  these  mechanisms  is  con- 
trolled and  coordinated  through  a  special  heat-regulating  center 
in  the  brain.  It  seems  necessary  to  assume  the  existence  of  some 
such  device  to  explain  the  almost  constant  balance  that  is  main- 
tained at  the  set  level  of  the  normal  body  temperature,  and  the 
alterations  in  this  level  which  we  witness  in  the  case  of  fevers  of 
different  intensities. 

Theories  of  Physiological  Oxidations. — Lavoisier  compared 
the  oxidations  in  the  body  to  the  oxidation  of  organic  substances 
in  combustions  at  high  temperatures.  He  supposed  that  the  mo- 
lecular oxygen  unites  directly  with  the  substances  oxidized  in  one 
case  as  in  the  other.  It  soon  became  evident,  however,  that  this 
direct  analogy  is  not  applicable.  The  material  that  is  oxidized 
in  the  body — fats,  carbohydrates,  proteins — is  consumed  with  a 
certain  rapidity, — in  the  case  of  muscular  contractions  with  great 
rapidity, — and  we  know  that  these  same  materials  out  of  the  body 
at  a  temperature  of  39°  C.  are  oxidized  with  extreme  slowness.  It 
became  customary,  therefore,  to  speak  of  the  oxidations  in  the  body 


974  NUTRITION    AND    HEAT    REGULATION. 

as  indirect,  meaning  thereby  that  the  material  is  not  acted  upon 
directly  by  the  molecular  oxygen.  Chemists  are  not  agreed  as  to 
the  exact  nature  of  simple  combustion,  and  it  is  therefore  increas- 
ingly difficult  to  compare  these  processes  with  the  oxidations  in  the 
body.  Leaving  aside  the  details  of  the  process,  it  may  still  be  be- 
lieved that  the  metabolism  of  material  in  the  body  by  means  of 
which  its  heat  energy  is  produced  is  at  bottom  comparable  to  ordi- 
nary combustions.  Oxygen  is  absolutely  necessary  to  the  process  in 
eacn  case;  the  same  end-products  are  formed  and  the  same  amount 
of  heat  is  liberated  in  the  one  case  as  in  the  other.  The  fundamental 
point  that  the  physiologist  is  attempting  to  solve  is  the  means  by 
which  the  body  accomplishes  these  oxidations  at  such  a  low  temper- 
ature. The  theories  suggested  to  explain  this  fact  have  changed 
naturally  with  the  advance  of  chemical  knowledge.  After  the  dis- 
covery of  ozone  (Schonbein,  1840)  and  its  great  power  of  oxidation  as 
compared  with  oxygen  it  was  suggested  that  in  some  way  the  oxy- 
gen in  the  body  is  ozonized  and  is  thus  able  to  burn  the  food  mate- 
rial. Gorup-Besanez  showed  that  some  of  the  oxidations  that  take 
place  in  the  body  can  be  successfully  accomplished  outside  the  body 
with  the  aid  of  ozone,  especially  in  the  presence  of  alkalies  or  alka- 
line carbonates.  Others  suggested  that  the  oxygen  in  the  body  be- 
comes converted  to  atomic  oxygen  and  is  thus  enabled  to  attack  the 
tissue  materials.  Hoppe-Seyler  formulated  a  theory  according  to 
which  the  living  molecule  is  first  split  into  smaller  molecules  by  the 
hydrolytic  action  of  ferments.  In  this  process,  as  in  fermentation,  to 
which  he  compared  it,  hydrogen  is  liberated  in  the  nascent  or  atomic 
state,  and  this  hydrogen  acting  upon  the  oxygen  forms  water  with 
the  liberation  of  some  atomic  oxygen,  which  in  turn  oxidizes  the 
split  products  of  the  fermentation.  Others  still  (Traube)  laid  stress 
upon  the  possibility  of  the  formation  of  hydrogen  peroxid  or 
similar  organic  peroxids  which  are  then  capable  of  effecting  the 
oxidation  of  the  body  material.  This  last  theory,  in  modified  form, 
still  prevails.* 

The  great  amount  of  experimental  and  theoretical  work  upon 
the  nature  and  cause  of  physiological  oxidations  has  established 
pretty  clearly  two  general  beliefs  which  it  is  important  to  keep 
in  mind.  It  has  been  shown,  in  the  first  place,  that  the  amount  of 
the  oxidation  is  governed  by  the  tissue  itself  and  not  by  the  quantity 
of  oxygen  present.  The  view  that  by  increasing  the  amount  of 
oxygen  offered  to  the  tissue  the  intensity  of  the  oxidations  can 
likewise  be  increased  was  formerly  held  and  is  still  met  with.  It 
is  often  supposed,  for  example,  that  by  breathing  pure  oxygen  the 
oxidations  of  the  body  may  be  augmented.  On  the  contrary,  the 

*  See  Engler  and  Weissberg,  "  Kritische  Studien  iiber  die  Vorgange  der 
A-utoxydation,"  1904. 


PHYSIOLOGICAL    OXIDATIONS.  975 

facts  indicate  that  when  a  sufficient  supply  of  oxygen  is  provided 
any  further  increase  has  no  immediate  effect  in  aiding  or  hastening 
the  oxidations.  The  intensity  of  the  process  is  conditioned  by  the 
tissue  itself.  The  initial  stimulus  or  substance  that  sets  going  the 
whole  reaction  arises  within  the  tissues.  The  second  generalization 
that  seems  to  be  accepted  more  and  more  of  recent  years  is  that  the 
oxidations  of  the  body,  those  reactions  that  give  rise  to  much  heat, 
do  not  affect  the  living  tissue  itself.  They  take  place  under  the 
influence  of  the  living  matter,  or  by  the  aid  of  substances  (enzymes) 
formed  by  the  living  matter,  but  the  material  actually  burnt  is  not 
organized  living  substance.  As  the  living  yeast  cells  break  down 
sugar  in  the  liquid  surrounding  them,  so  the  living  tissue  cells  metab- 
olize and  oxidize  the  dead  food  material  contained  in  the  lymph 
and  tissue  liquid  in  which  they  are  bathed.  The  opposite  point  of 
view  was  ably  advocated  by  Pfluger.  This  observer,  in  fact,  ex- 
plained the  mystery  of  physiological  oxidations  by  assuming  that 
the  oxygen  together  with  the  food  material  is  synthesized  into  the 
highly  complex  and  unstable  living  molecules.  The  active  intra- 
molecular movement  within  these  molecules  leads  constantly  to  a 
breaking  down,  a  splitting  off  of  simpler  molecules  which  consti- 
tute the  products  of  physiological  oxidation.  The  instability  of 
the  molecule  is  due  to  its  size  and  the  activity  of  the  intramolecular 
movements,  or,  as  Pfluger  expressed  it,  "The  intramolecular  heat 
of  the  cell  is  its  life."  This  point  of  view,  however,  has  not  found 
acceptance.  It  is  implied  or  stated  by  most  recent  authors  that 
the  food  material  is  attacked  and  oxidized  outside  the  living 
molecule,  in  the  form  of  fat,  sugar,  protein,  or  rather  in  the  form 
of  the  intermediary  products  arising  in  the  metabolism  of  these 
substances.  The  tendency  for  many  years  has  been  to  show  that 
these  processes  in  the  body  are  chemical  changes  that  do  not  differ 
fundamentally  from  similar  processes  outside  the  body.  The 
point  of  view  actually  adopted  by  most  workers  is  that  the  living 
matter  effects  its  wonderful  changes  in  the  food  material  by  making 
use  of  intracellular  ferments  or  enzymes  (endo-enzymes).*  That 
such  enzymes  are  formed,  one  may  say,  generally  in  the  tissues 
of  the  body,  has  been  brought  out  in  the  preceding  chapters  upon 
Digestion  and  Nutrition.  It  is  necessary  only  to  recall  the  facts 
that  lipase,  the  fat-splitting  enzyme,  has  been  isolated  from  many 
tissues,  and  that  in  the  liver  and  muscles  and  probably  other  tissues 
there  exist  enzymes  capable  of  converting  glycogen  to  sugar  or 
the  reverse,  and  of  oxidizing  the  sugar  completely  by  the  serial 
action  of  several  intracellular  enzymes.  Finally,  with  regard  to 
the  protein  material,  it  is  now  recognized  that  proteolytic  enzymes 
exist  in  many,  if  not  all,  of  the  living  tissues.  This  point  is  demon- 
*  For  literature,  see  Vernon,  "Intracellular  Enzymes,"  London,  1908. 


976  NUTRITION    AND    HEAT    REGULATION. 

strated  by  the  fact  of  autolysis, — that  is,  if  living  tissue  is  taken 
from  the  body,  with  precautions  against  contamination  by  bac- 
teria, and  while  under  perfect  aseptic  conditions  is  kept  warm 
and  moist,  it  will  digest  itself.  The  protein  is  split  up  into  the  same 
simple  hydrolytic  products  as  are  obtained  by  boiling  it  with 
acids.  It  has  been  shown  that  this  digestion  is  due  to  enzymes — 
autolytic  enzymes — formed  within  the  living  tissue.  There  is  no 
doubt,  therefore,  of  the  existence  of  intracellular  enzymes,  and  that 
these  substances  play  a  conspicuous  part  in  the  metabolism  of  food 
material.  The  lipase,  the  diastase,  and  the  autolytic  enzymes 
(proteases)  just  referred  to  all  belong  to  the  group  that  cause 
hydrolytic  cleavages — that  is,  they  induce  splitting  or  decompo- 
sition of  the  material  by  a  reaction  with  water.  The  supposition 
has  naturally  been  made  that  probably  the  oxidations  of  the  body 
are  effected  also  by  enzymes  which  in  some  way  activate  the 
oxygen.  Enzymes  of  this  character  have  been  found;  they  are 
designated  in  general  as  oxidases  or  as  oxidases  and  peroxidases, 
the  former  term  referring  to  those  enzymes  that  effect  oxidations 
in  the  presence  of  oxygen,  while  the  latter  is  applied  to  certain 
enzymes  supposed  to  act  only  in  the  presence  of  peroxids.  Bach 
and  Chodat*  have  simplified  this  conception  by  the  hypothesis 
that  all  the  oxidizing  enzymes  of  the  tissues  are  peroxidases,  that  is 
to  say,  substances  which  have  the  power  of  liberating  active  oxygen 
from  hydrogen  peroxide  or  similarly  constituted  organic  peroxides. 
They  assume  that  there  are  present  in  the  tissues  certain  organic 
substances  produced  by  the  cells,  which  take  up  oxygen  to  form 
compounds  of  the  nature  of  peroxides,  and  which  they  designate 
as  oxygenases.  These  oxygenases  or  organic  peroxides  when  acted 
upon  by  the  peroxidase  give  up  oxygen  in  active  form,  which  then 
effects  the  oxidations.  If  potato  peelings,  for  example,  are  extracted 
with  water,  the  extract  itself  is  not  able  to  cause  oxidation  of  easily 
oxidizable  substances  such  as  pyrogallol.  But  if  this  extract  is 
mixed  with  the  residue,  or  with  a  solution  of  hydrogen  peroxide, 
active  oxidations  can  be  produced.  Using  the  above  terminology 
the  aqueous  extract  of  the  potato  peelings  contains  the  enzyme, 
peroxidase.  This  enzyme  in  the  presence  of  hydrogen  peroxide, 
or  a  similarly  constituted  organic  peroxide,  such  as  the  oxygenase 
assumed  to  exist  in  the  residue  in  the  above  experiment,  sets  free 
atomic  oxygen  and  thus  brings  about  physiological  oxidations. 
This  view  can  be  represented  schematicalty  by  the  following 
equations,  in  which  P  represents  the  peroxidase;  B,  the  material 
which  undergoes  oxidation,  and  A,  the  material  in  the  tissues 
which  takes  up  oxygen  to  form  a  peroxide: 

A     +     O2     =     AO2  (organic  peroxide  or  oxygenase) 

AO2     +     P     +     B     =     BO     +    AO     +     P 
*  Bach,  "Handbuch  d.  Biochemie,  Erganzungsband,"  1913. 


PHYSIOLOGICAL    OXIDATIONS.  977 

Or,  as  seems  probable  from  some  recent  experiments,*  the  peroxidase 
may  first  combine  with  the  oxygen  of  the  oxygenase  to  form  a  per- 
oxide, which  then  reacts  with  the  oxydizable  material  in  the  tissues. 

P    +    AO2    = .  PO2    +    A 
B     +    PO2     =     PO     +    BO  or  P    +    2BO 

This  view  simplifies  the  somewhat  confusing  distinction  made  in 
the  literature  between  oxidases,  or  enzymes  which  act  in  the  pres- 
ence of  oxygen,  and  peroxidases  which  act  only  in  the  presence  of 
peroxides,  since  it  is  assumed  that  oxidases,  properly  speaking,  do 
not  exist.  What  has  been  designated  as  an  oxidase  or  a  direct 
oxidase  is  simply  a  mixture  of  a  peroxidase  and  an  oxygenase.  It 
has  been  found  that  many  of  the  characteristic  oxidations  that 
occur  in  the  body,  such  as  the  oxidation  of  the  fatty  acids  at  the 
/3-carbon  atom  in  the  chain,  the  oxidation  of  glucose  to  glycuronic 
acid,  etc.,  may  be  imitated  outside  the  body  by  oxidation  with 
hydrogen  peroxide,  but  not  by  other  oxidizing  agents,  f  This 
collateral  evidence  gives  important  support  to  the  theory.  Per- 
oxidases have  been  discovered  in  the  blood,  milk,  and  in  several 
of  the  tissues  of  the  body,  such  as  the  lymphocytes,  sperm  cells, 
etc.J  They  can  be  tested  for  by  a  number  of  reactions,  chiefly 
color  reactions,  such  as  the  bluing  of  a  tincture  of  guaiacum  in  the 
presence  of  a  peroxide  or  the  conversion  of  a  colorless  or  leucobase  to 
a  colored  oxidation  product.  Some  of  these  peroxidases  have  been 
given  specific  names  in  accordance  with  the  particular  compounds 
whose  oxidation  they  effect.  For  example,  xanthinoxidase,  which 
effects  the  oxidation  of  hypoxanthin  and  xanthin  to  uric  acid;  the 
glycolytic  oxidase  or  oxidases,  which  effect  the  oxidation  of  the 
intermediary  products  of  sugar  metabolism  in  the  tissues;  tyrosin- 
ase,  which  effects  the  oxidation  of  tyrosin,  and  in  this  way  is  sup- 
posed by  many  observers  to  give  rise  to  various  animal  pigments, 
such  as  melanin;  the  aldehydases,  which  effect  the  oxidation  of  alde- 
hydes to  their  corresponding  acids — salicylic  aldehyd,  for  instance, 
to  salicylic  acids.  In  practically  all  of  the  tissues  there  exists  an 
enzyme  which  is  capable  of  breaking  up  hydrogen  peroxide  with 
the  liberation  of  oxygen.  The  evolution  of  oxygen  is  readily  seen 
when  a  solution  of  hydrogen  peroxide  is  brought  into  contact  with 
a  living  tissue.  This  peroxidase  has  been  given  a  special  name, 
catalase,  but  its  relations  to  the  processes  of  physiological  oxidation 
have  been  interpreted  in  different  ways  by  the  various  workers  in 
this  field.  Burge  §  has  brought  forward  considerable  experimental 

*Reed,  "Botanical  Gazette,"  vol.  62,  1916. 

f  Consult  Dakin,  "Oxidations  and  Reductions  in  the  Animal  Body,"  1912. 
t  For  discussion  and  literature  consult  Kastle,  "The  Oxidases,"  Bulletin 
No.  59,  1910,  Hygienic  Laboratory,  Washington,  D.  C.;  also  Bach,  loc.ciL 
§  Burge,  "American  Journal  of  Physiology,"  vols.  41-43,  1916,  1917. 
62 


978  NUTRITION    AND    HEAT    REGULATION. 

evidence  to  show  that  the  amount  of  catalase  in  a  tissue  or  an  ani- 
mal varies  directly  with  the  intensity  of  the  processes  of  oxidation, 
and.  moreover,  that  in  any  given  tissue,  the  skeletal  muscles,  for 
example,  the  amount  present  may  be  increased  by  exercise  and 
decreased  by  inaction  or  starvation.  This  evidence  would  seem 
to  connect  the  catalase  in  a  direct  way  with  the  processes  of  phys- 
iological oxidation  and  show  that  there  is  an  adaptive  reaction 
by  means  of  which  the  quantity  varies  to  correspond  with  the 
needs  of  the  organism.  The  oxidations  effected  by  this  means 
are  the  principal  source  of  the  development  of  heat  in  the  body — 
they  are  especially  exothermic  reactions.  Many  other  of  the 
chemical  changes  of  metabolism,  such  as  the  hydrdlytic  cleavages, 
liberate  but  little  heat,  and  others  still,  such  as  the  syntheses  of 
one  kind  or  another  in  which  there  is  a  union  of  compounds  to 
form  more  complex  substances,  may  even  be  attended  by  an 
absorption  of  heat,  that  is,  a  conversion  of  heat  energy  to  the  energy 
of  chemical  affinity.  The  oxidizing  reactions  constitute,  therefore, 
a  large  and  very  characteristic  feature  of  the  metabolism  of  the 
warm-blooded  animals.  The  heat  thus  produced  by  the  oxidation 
of  our  food  material  serves  to  maintain  the  body  temperature  at 
its  normal  high  level,  and  establishes  a  temperature  environment 
at  which  the  enzymatic  and  chemical  metabolism  of  the  tissues 
is  at  its  optimum. 


SECTION  IX. 
THE  PHYSIOLOGY  OF  REPRODUCTION. 

With  the  exception  of  the  phenomenon  of  consciousness,  no 
fact  of  life  excites  more  interest  and  seems  to  offer  greater  diffi- 
culties to  an  adequate  explanation  than  the  function  of  reproduc- 
tion. The  male  cell  (spermatozoon)  and  the  female  cell  (ovum) 
unite  to  form  a  new  cell  which  thereupon  begins  to  grow  rapidly 
and  produces  an  organism  that  in  all  of  its  manifold  peculiarities 
of  structure  and  function  is  essentially  a  replica  of  its  parents. 
The  fundamental  problems  presented  in  this  act  of  reproduction 
are  those  of  fertilization  and  heredity.  In  the  former  we  must 
ascertain  why  the  union  of  the  two  cells  is  necessary  or  advanta- 
geous, and  the  secret  of  the  stimulating  influence  upon  growth  that 
arises  from  this  union.  Under  the  term  heredity  we  express  the  obvi- 
ous, yet  mysterious  fact  that  the  fertilized  ovum  of  each  species  de- 
velops into  a  structure  like  that  of  its  parents.  Both  of  these  im- 
portant problems  are  essentially  of  a  physiological  character, — that 
is,  they  deal  with  properties  of  the  living  material  composing  the 
reproductive  cells;  but,  at  present,  biological  investigation  along 
these  lines  is  largely  in  the  morphological  stage.  The  part  of  the  sub- 
ject that  can  be  studied  with  most  success  is  the  structural  changes 
that  are  associated  with  fertilization  and  reproduction.  Great, 
indeed  wonderful,  progress  has  been  made  during  the  last  century, 
but  it  is  needless  perhaps  to  say  that  much  remains  unexplained, 
and  that  in  this,  as  in  so  many  other  problems  of  nature,  the  greater 
our  knowledge  the  clearer  becomes  our  vision  of  the  difficulties  and 
complexities  of  a  final  scientific  explanation.  Outside  these  funda- 
mental problems  there  are  other  accessory  functions  connected,  for 
instance,  with  the  external  genital  organs  which  in  a  measure  are  of 
more  immediate  practical  interest.  In  one  way  or  another  these 
functions  are  necessary  or  helpful  to  the  final  union  of  the  repro- 
ductive cells.  They  form  a  part  of  the  reproductive  life  which  comes 
more  immediately  under  our  observation  and  control,  and  consti- 
tute, therefore,  a  subject  which  has  been  more  accessible  to  in- 
vestigation. In  the  brief  treatment  given  in  the  following  chap- 
ters more  emphasis  is  laid  upon  this  side,  the  accessory  phenomena 
of  reproduction,  than  upon  the  deeper,  more  fundamental  prob- 

980 


THE  FEMALE  REPRODUCTIVE  ORGANS.  981 

iems,  in  view  of  the  fact  that  the  accessory  phenomena  are  the  ones 
ivhich  have  at  present  the  greater  practical  interest. 

The  function  of  reproduction  is  often  omitted  from  physiolog- 
ical courses,  and  the  reason  perhaps  is  partly  that  the  structural 
features  and  the  development  of  the  embryo  have  been  assigned  to 
the  department  of  anatomy,  and  partly  because  it  is  a  function 
not  essential  to  the  maintenance  of  the  existence  and  reactions  of 
the  organism.  The  reproductive  organs  might  be  eliminated  en- 
tirely and  the  power  of  tlie  body  as  an  organism  to  maintain  its 
individual  existence  not  be  seriously  interfered  with.  The  physio- 
logical importance  of  the  reproductive  organs  lies  not  in  their 
co-operation  in  the  communal  life  of  the  various  parts  of  the  body, 
but  in  their  adaptation  to  produce  another  similar  being.  We 
may  explain,  therefore,  the  co-ordinating  mechanisms  of  the 
body  without  reference  to  the  reproductive  tissues,  except  so  far 
as  their  supposed  internal  secretions  affect  general  or  specific 
metabolism. 


CHAPTER  LII. 

PHYSIOLOGY  OF  THE  FEMALE  REPRODUCTIVE 
ORGANS, 

The  Graafian  Follicle  and  the  Corpus  Luteum. — The  functional 
value  of  the  ovary  is  connected  with  the  formation  and  rupture 
of  the  Graafian  follicles,  whereby  an  ovum  is  liberated.  The  pri- 
mordial follicles  consist  of  an  ovum  surrounded  by  a  layer  of  fol- 
licular  epithelium.  Beginning  at  a  certain  time  after  birth  and 
continuing  throughout  the  period  of  active  sexual  life,  some  of  these 
primordial  follicles  develop  into  mature  Graafian  follicles  and  mi- 
grate to  the  surface  of  the  ovary.  The  change  consists  in  a  pro- 
liferation of  the  follicular  epithelium  and  the  formation  of  a  serous 
liquid,  the  liquor  folliculi,  between  the  layers  of  this  epithelium. 
In  the  matured  follicle  there  is  a  connective  tissue  covering,  the 
theca  folliculi,  formed  from  the  stroma  of  the  ovary  and  consisting 
of  two  eoats  or  tunics — the  external  and  the  internal.  The  cells 
in  the  internal  tunic  develop  a  yellowish  pigment  as  the  follicle 
grows,  and  are  sometimes  designated  as  lutein  cells.  Within  the 
capsule  formed  by  the  internal  tunic  there  is  a  layer  of  follicular 
cells  known  as  the  membrana  granulosa  and  attached  to  one  side 
is  a  mass  of  the  same  cells,  the  discus  proligerus — within  which 
the  ovum  is  imbedded.  The  follicular  liquid  lies  between.  This 
liquid  increases  in  amount,  and  when  the  follicle  has  reached  the 


982  THE    PHYSIOLOGY    OF   REPRODUCTION. 

surface  it  forms  a  vesicle  projecting  to  the  exterior.  This  projecting 
portion  is  nearly  bloodless  and  thinner  than  the  rest  of  the  wall  of 
the  follicle.  It  is  designated  as  the  stigma.  When  fully  mature  the 
follicle  ruptures  at  the  stigma  and  the  egg,  together  with  the  sur- 
rounding follicular  cells  of  the  discus  proligerus  and  a  portion  of  the 
membrana  granulosa,  is  extruded,  the  egg  being  received  into  the 
open  end  of  the  Fallopian  tube.  According  to  Clark,*  the  rupture  of 
the  follicle  is  brought  about  by  an  increasing  vascular  congestion 
of  the  ovary.  The  tension  within  the  ovary  is  thereby  increased, 
the  follicle  is  forced  to  the  surface,  and  the  circulation  at  the  most 
projecting  portion  is  interfered  with  to  such  an  extent  as  to  cause 
necrotic  changes  at  the  stigma,  at  which  rupture  finally  occurs.  After 
the  bursting  of  the  follicle  its  walls  collapse,  and  the  central  cavity 
receives  also  some  blood  from  the  ruptured  vessels  of  the  theca. 
Later  on  the  vesicle  becomes  filled  with  cells  containing  a  yellow 
pigment.  These  cells  increase  rapidly  and  form  a  festooned  border 
of  increasing  thickness  around  the  central  blood  clot.  The  vesicle 
at  this  stage,  on  account  of  the  yellow  color  of  the  new  cells,  is 
known  as  a  corpus  luteum.  The  structure  thus  formed  increases 
in  size  for  a  period  and  then  undergoes  retrogressive  changes  and 
is  finally  completely  absorbed.  The  duration  of  the  period  of  growth 
and  retrogression  varies  according  as  the  egg  liberated  becomes 
fertilized  or  not.  If  fertilization  does  not  occur,  as  is  the  case  in 
the  usual  monthly  periods,  the  corpus  luteum  reaches  its  maximum 
size  within  two  to  three  weeks  and  then  begins  to  be  absorbed. 
It  is  frequently  designated  under  these  circumstances  as  the  false 
corpus  luteum  (corpus  luteum  spurium)  or  corpus  luteum  of  men- 
struation. In  case  the  egg  is  fertilized  and  the  woman  becomes 
pregnant  the  life  history  of  the  corpus  luteum  is  much  prolonged. 
Instead  of  undergoing  absorption  after  the  third  week  it  continues 
to  increase  in  size  by  multiplication  of  the  lutein  cells  during  the 
first  few  months  of  pregnancy,  and  does  not  show  retrogressive 
changes  until  the  sixth  month  or  later.  The  total  size  of  the  corpus 
in  such  cases  is  much  larger  than  in  menstruation,  and  it  was  des- 
ignated, therefore,  by  the  older  writers  as  the  true  corpus  luteum 
(corpus  luteum  verum)  or  corpus  luteum  of  pregnancy.  Later 
observers  agree  that  there  is  no  essential  difference  in  structure 
between  the  true  and  the  false  corpus  luteum,  although  the  former 
has  a  longer  history  and  attains  a  greater  size.  The  point  of 
greatest  structural  interest  in  the  corpus  luteum  is  the  origin  of  the 
yellow  (lutein)  cells.  Histologists  have  been  and  still  are  divided 
upon  this  point ;  some  believe  that  they  arise  from  the  cells  of  the 
membrana  granulosa,  others  that  they  come  from  the  connective 
tissue  cells  in  the  internal  capsule  (theca  interna)  of  the  follicle. 
*  Clark,  "Johns  Hopkins  Hospital  Reports/'  7,  181,  1898. 


THE    FEMALE    REPRODUCTIVE    ORGANS.  983 

The  majority  of  writers  seem  to  favor  the  latter  view.*  Regarding 
the  physiological  importance  of  the  corpus  opinions  also  differ. 
Some  regard  it  as  simply  a  protective  mechanism  by  means  of 
which  the  empty  space  in  the  follicle  is  rilled  up  by  a  tissue  which  is 
afterward  easily  absorbed,  instead  of  by  scar  tissue.  Others,  how- 
ever, attribute  to  the  lutein  cells  secretory  functions  of  the  most 
important  character  in  connection  with  the  subsequent  develop- 
ment of  the  egg  and  the  activities  of  the  uterus.  Some  reference 
will  be  made  to  these  views  farther  on. 

Menstruation. — The  attainment  of  sexual  maturity  or  puberty 
is  marked  by  a  number  of  visible  changes  in  the  body,  but  in  the 
female  the  characteristic  change  is  the  appearance  of  the  men- 
strual flow  from  the  uterus.  The  age  at  which  this  phenomenon 
occurs  shows  many  individual  variations,  but  the  average  for 
temperate  climates  is  given  usually  at  14  to  15  years.  In  the 
warmer  countries  the  age  is  earlier, — 8  to  10  years, — and  in  the  cold 
regions  somewhat  later, — 16  years.  The  racial  characteristic  in 
this  respect  is  said  to  be  maintained,  however,  after  generations  of 
residence  in  countries  of  a  different  climate,  as  is  illustrated  by  the 
relatively  early  appearance  of  menstruation  among  Jews  even  in 
the  colder  countries.  After  the  phenomenon  appears  it  occurs  at 
regular  intervals  of  28  days,  more  or  less,  and  hence  is  known  as 
the  monthly  period,  menses,  menstruation,  or  catamenia.  The 
interval  is  not  absolutely  regular,  and  shows  many  individual 
variations  within  limits  which  may  be  placed  at  20  to  35  days. 
Absence  of  the  menstrual  flow  is  designated  as  a  condition  of  amen- 
orrhea.  Certain  premonitory  symptoms  usually  precede  the 
appearance  of  the  menses,  such  as  pains  in  the  back  or  head  or 
a  general  feeling  of  discomfort,  although  in  some  cases  these  symp- 
toms are  absent.  When  these  premonitory  symptoms  are  unusually 
painful  or  serious  and  the  flow  is  difficult  or  irregular  the  condition 
is  designated  as  dysmenorrhea.  The  flow  begins  with  a  discharge  of 
mucus,  which  later  becomes  mixed  with  blood.  The  quantity  of 
blood  lost  is  subject  to  individual  variations,  but  it  may  amount  to 
as  much  as  100  to  200  gms.  The  flow  continues  for  3  or  4  days 
and  then  subsides.  Under  normal  conditions  this  phenomenon 
occurs  regularly  throughout  sexual  life, — that  is,  during  the  period 
in  which  conception  is  possible.  If  fertilization  occurs,  men- 
struation is  suspended  during  pregnancy  and  the  period  of  lacta- 
tion. At  the  forty-fifth  to  the  fiftieth  year  menstruation  disap- 
pears permanently,  and  this  change  marks  what  is  known  as  the 
natural  menopause,  climacteric,  or  change  of  life.  The  change  is 
sometimes  abrupt,  sometimes  very  gradual,  being  preceded  by  irreg- 

*  For  discussion  and  literature  see  Marshall,  "The  Physiology  of  Repro- 
duction," London,  1910;  and  Loeb,  "Journal  of  the  American  Medical  Associa- 
tion," 1906,  xlvi.,  416. 


984  THE    PHYSIOLOGY    OF    REPRODUCTION. 

ularities  in  menstruation,  and  it  is  not  infrequently  associated 
with  psychical  and  physical  disturbances  of  a  serious  character. 
If  at  any  time  during  sexual  life  the  ovaries  are  completely  re- 
moved by  surgical  operation  menstruation  is  brought  to  a  close, 
this  condition  being  designated  as  artificial  menopause. 

Structural  Changes  in  the  Uterus  During  Menstruation. — Men- 
struation is  a  phenomenon  of  the  uterus.  The  lining  mucous  mem- 
brane, the  endometrium,  in  the  period  of  four  or  five  days  preceding 
the  flow,  becomes  rapidly  thicker  and  its  superficial  layers  are  con- 
gested with  blood,  and  indeed  in  places  small  collections  of  blood 
may  be  noticed.  Opinions  differ  very  much  as  to  the  change  under- 
gone by  this  thickened  membrane  during  the  flow.  According  to 
some  authors,  most  of  the  membrane  is  thrown  off  and  the  blood 
escapes  from  the  denuded  surface  mixed  with  pieces  of  the  mem- 
brane. According  to  others,  no  material  destruction  of  the  mem- 
brane occurs,  the  blood  that  escapes  being  due  to  small  capillary 
extravasations  or  perhaps  mainly  to  a  process  of  diapedesis.  It 
would  seem  that  the  amount  of  destruction  of  the  endometrium 
must  be  subject  to  individual  variations.  After  the  cessation  of 
the  flow  the  mucous  membrane  is  rapidly  repaired  by  regenerative 
changes  in  the  tissues;  the  surface  epithelium,  if  denuded,  is  re- 
placed by  proliferation  of  the  cells  lining  the  uterine  glands  and 
the  thickened,  edematous  condition  of  the  membrane  rapidly  sub- 
sides during  a  period  of  six  or  seven  days.  While  the  escape  of 
blood  takes  place  only  from  the  surface  of  the  uterus,  the  other 
reproductive  organs — the  ovary,  the  Fallopian  tubes,  and  even  the 
external  genital  organs — share  to  some  extent  in  the  vascular  con- 
gestion exhibited  by  the  uterus  during  the  period  preceding  the 
menstrual  flow.  The  mucous  membrane  of  the  uterus  may  be  said 
to  exhibit  a  constantly  recurring  menstrual  cycle  which  falls  into 
four  periods:  (1)  Period  of  growth  in  the  few  (5)  days  preceding 
menstruation,  characterized  by  a  rapid  increase  in  the  stroma, 
blood-vessels,  epithelium,  etc.,  of  the  membrane.  (2)  The  men- 
struation or  period  of  degeneration  (4  days),  during  which  the 
capillary  hemorrhage  takes  place  and  the  epithelium  suffers  de- 
generative changes  and  is  cast  off  more  or  less.  (3)  The  period  of 
regeneration  (7  days),  during  which  the  mucous  membrane  returns 
to  its  normal  size.  (4)  The  period  of  rest  (12  days),  during  which 
the  endometrium  remains  in  a  quiescent  condition. 

The  Phenomenon  of  Heat  (CEstrus)  in  Lower  Mammals. — 
The  phenomenon  known  as  heat  in  lower  mammals  resembles,  in 
many  essential  respects,  menstruation  in  human  beings,  and  they 
may  be  regarded  as  homologous  functions.  Heat  is  a  period  of 
sexual  excitement  which  occurs  one  or  more  times  during  the  year 
and  during  which  the  female  will  take  the  male.  The  condition 


THE  FEMALE  REPRODUCTIVE  ORGANS.  985 

lasts,  as  a  rule,  for  several  days,  and  in  the  female  is  accompanied 
by  changes  which  resemble  those  of  menstruation.  The  external 
genital  organs  become  swollen  and  in  many  animals  there  is  a 
discharge  of  mucus  or  mucus  and  blood  from  the  uterus.  His- 
tologically  the  mucous  membrane  of  the  uterus  undergoes  changes 
similar  to  those  of  menstruation — that  is,  the  membrane  increases 
in  size  and  becomes  congested  with  blood — and  it  exhibits  a  phase 
of  degeneration  during  whjch  some  of  the  epithelial  lining  may  be 
cast  off  and  some  hemorrhage  occur.  As  in  the  case  of  the  men- 
strual period,  the  heat  period  or  oestrous  cycle  may  be  divided  into 
four  subperiods  (Marshall  and  Jolly) :  the  prooestrum,  during  which 
the  genital  organs  are  congested  and  bleeding  occurs,  corresponds 
with  menstruation;  the  oestrus,  the  period  of  sexual  desire;  the 
metcestrum,  the  period  of  repair  and  return  to  normal  conditions, 
and  the  anoestrum,  the  period  of  rest.  If  sexual  union  is  prevented 
during  this  period  heat  passes  away  in  a  few  days,  but  recurs  again 
at  intervals  which  vary  in  the  different  mammals:  4  weeks  in  the 
monkey,  mare,  etc.;  3  to  4  weeks  in  the  cow;  2J  to  4  weeks  in  the 
sheep;  9  to  18  days  in  the  sow;  12  to  16  weeks  in  the  bitch,  etc. 
The  recurrence  of  the  period  under  these  circumstances  suggests 
at  once  the  essential  resemblance  to  the  monthly  periods  of  women. 
According  to  Heape's  most  interesting  observations  upon  monkeys 
(Semnopithecus),*  some  of  these  animals  show  a  regular  monthly 
flow  lasting  for  4  days,  except  when  conception  takes  place.  The 
changes  during  heat  must  be  considered  as  physiologically  ho- 
mologous to  those  of  menstruation.  The  sexual  excitement  that 
attends  the  condition  in  the  lower  animals  is  not  distinctly  repre- 
sented in  man,  although  it  is  commonly  said  that  in  the  period 
following  menstruation  the  sexual  desire  is  stronger  than  at  other 
times,  but  in  the  changes  undergone  by  the  uterus  and  the  fact 
that  these  changes  are  connected,  as  a  rule,  with  the  liberation 
of  an  egg  from  the  ovary  (ovulation),  the  two  phenomena  are 
physiologically  similar. 

Relation  of  the  Ovaries  to  Menstruation. — It  appears  to  be 
clearly  demonstrated  that  the  phenomenon  of  menstruation  is  de- 
pendent upon  a  periodical  activity  in  the  ovaries.  When  the 
ovaries  are  completely  removed  menstruation  ceases  (artificial 
menopause)  and  the  uterus  undergoes  atrophy.  When  the  ovaries 
are  congenitally  lacking  or  rudimentary,  a  condition  of  amenorrhea 
also  exists.  These  facts  and  the  connection  of  the  ovaries  with 
menstruation  are  further  corroborated  in  a  striking  way  by  experi- 
ments upon  transplantation  or  grafting  of  the  ovary.  This  experi- 
ment has  been  performed  upon  lower  animals  (apes)  as  well  as  upon 

*Heape,  "Philosophical  Transactions,  Royal  Society,"  185  (B),  1894, 
and  188  (B),  1897. 


986  THE    PHYSIOLOGY    OF    REPRODUCTION. 

human  beings.  Removal  of  both  ovaries  in  apes  is  followed  by  a  ces- 
sation of  menstruation.  Transplantation  of  an  ovary  under  the  skin 
serves  to  maintain  menstruation,  but  if  subsequently  removed  this 
function  disappears.*  In  the  human  being  Morris  and  Glass  ob- 
tained similar  results,  f  An  ovary  or  a  piece  of  an  ovary  trans- 
planted into  the  uterus  itself  or  the  broad  ligament  caused  a  re- 
turn of  the  menstrual  periods  which  had  ceased  after  surgical  re- 
moval of  the  glands,  or  brought  on  free  menstruation  in  conditions 
of  amenorrhea  or  dysmenorrhea. 

Many  views  have  been  proposed  to  explain  this  relationship 
between  ovary  and  uterus.  In  most  cases  it  has  been  assumed 
{hat  the  menstruation  in  the  uterus  is  connected  with  the  act  of 
ovulation, — that  is,  the  ripening  and  discharge  of  a  Graafian  follicle. 
Gynecologists,  it  is  true,  have  accumulated  facts  to  show  that  ovu- 
lation may  occur  independently  of  menstruation,  but,  as  a  rule, 
the  two  acts  occur  together,  not  simultaneously,  but  in  a  definite 
sequence,  and  the  significance  of  menstruation  is  to  be  found  in  its 
physiological  connection  with  the  fate  of  the  ovum.  It  was 
believed  at  first  that  the  processes  in  the  ovary  influence  the 
uterus  by  a  nervous  reflex.  This  view  finds  its  most  complete 
expression  in  the  theory  formulated  by  Pfliiger.  According  to  this 
physiologist,  the  congestion  of  the  uterus  which  leads  to  menstrua- 
tion and  the  congestion  of  the  ovary  which  leads  to  ovulation  are 
both  reflex  vasodilator  effects  due  to  the  mechanical  stimulation 
of  the  sensory  nerves  of  the  ovary  by  the  growth  in  size  of  the  fol- 
licle. As  this  structure  develops  the  mechanical  stimulus  increases 
in  intensity,  the  congestion  in  both  organs  becomes  more  pro- 
nounced and  leads  finally  to  the  bursting  of  the  follicle  and  the 
hemorrhage  in  the  uterus.  This  very  attractive  theory  does  not, 
however,  accord  with  the  facts.  Goltz  and  ReinJ  have  shown  by 
experiments  upon  dogs  that  when  the  nerves  going  to  the  uterus 
are  completely  severed  from  their  central  connections  the  animals 
can  be  fertilized,  become  pregnant,  and  give  birth  to  a  litter  of 
young.  Moreover,  the  experiments  upon  transplantation  referred 
to  above  seem  to  show  quite  conclusively  that  a  nervous  connection 
is  not  essential  to  the  influence  that  the  ovary  exerts  upon  the 
uterus.  The  present  view,  therefore,  is  that  this  influence  is  exerted 
through  the  blood, — the  other  great  system  connecting  the  organs 
with  one  another.  The  usual  assumption  is  that  the  ovaries  form  an 
internal  secretion  which  is  given  to  the  blood  or  lymph  and  upon 
reaching  the  uterine  tissues  serves  to  stimulate  the  mucous  mem- 
brane to  a  more  active  growth.  This  theory  has  been  elaborated 

*Halban,  "Deutsche  Gesellschaft  f .  Gynakol. ."  9,  1901. 

t  Glass,  "Medical  News,"  523,  1899;  Morris,  "Medical  Record,"  83,  1901. 

t  Rein  "  Archiv  f.  die  gesammte  Physiologic,"  vol.  xxiii. 


THE  FEMALE  REPRODUCTIVE  ORGANS.  987 

most  fully  perhaps  by  Fraenkel,*  who  believes  that  this  internal 
secretion  is  furnished  by  the  yellow  cells  of  the  corpus  luteum. 
This  observer,  from  the  results  of  operations  upon  women,  believes 
that  the  ovum  is  normally  discharged  two  weeks  before  menstrua- 
tion, and  the  resulting  increased  activity  of  the  cells  of  the  corpus 
luteum  is  responsible  for  the  secretion  which  stimulates  the  uterus 
to  the  augmented  growth  that  takes  place  in  the  premenstrual 
period.  Whether  or  not  the  monthly  change  in  the  endometrium 
is  directly  dependent  upon  an  internal  secretion  from  the  ovary  or 
is  an  independent  cyclic  process  peculiar  to  this  tissue,  there  seems 
to  be  no  doubt  that  the  physiological  integrity  of  the  uterus  as  a 
whole  is  dependent  upon  the  ovaries.  Removal  of  the  ovaries 
in  the  young  prevents  the  normal  development  of  the  uterus, 
while  removal  in  the  adult  causes  a  degeneration  of  the  uterus, 
which,  however,  can  be  averted  by  a  successful  transplantation 
of  ovarian  tissue,  f  In  the  lower  animals  Marshall  and  Jolly { 
have  been  able  to  show  that  extracts  of  the  ovaries,  taken  from 
an  animal  in  or  just  before  heat  (prooestrous  or  oestrous  period), 
when  injected  into  an  animal  during  the  ancestrum  bring  on  a 
transient  condition  of  heat.  These  authors  do  not  believe,  how- 
ever, that  the  chemical  stimulus  (hormone)  formed  in  the  ovary 
is  developed  by  the  cells  of  the  corpus  luteum,  since  according 
to  their  observation  on  cats  and  dogs  ovulation  does  not  occur 
until  after  heat  has  begun  (prooestrum) ;  nor  does  it  depend  upon 
the  mere  maturation  of  the  follicles,  since  when  these  are  opened 
by  puncture,  some  time  before  maturation,  heat  appears  in  due 
season. 

The  Physiological  Significance  of  Menstruation. — Naturally 
many  views  have  been  proposed  to  explain  the  significance  of  men- 
struation. According  to  the  Mosaic  law,  it  is  a  process  of  purifica- 
tion; others  have  seen  in  it  a  mechanism  to  remove  an  excess  of 
nutriment  in  the  body;  but  since  the  period  in  which  our  knowl- 
edge of  the  structure  of  the  organs  concerned  and  of  the  histo- 
logical  changes  during  the  act  became  more  definite,  theories  of  the 
meaning  of  menstruation  have  usually  assumed  that  it  is  a  prepara- 
tion for  the  reception  of  the  fertilized  ovum.  These  views  have 
taken  two  divergent  forms  according  as  the  act  of  ovulation  was 
believed  to  precede  or  to  happen  simultaneously  with  or  subse- 
quently to  the  act  of  menstruation.  According  to  one  view,  the 

*  Fraenkel,  "Archiv  f .  Gynakologie,"  68,  2,  1903.  See  also  Ihm,  "Monat- 
schrift  f.  Geburtshiilfe  u.  Gynakol.,"  21,  515,  1905,  for  discussion  and  extensive 
literature. 

f  Carmichael  and  Jolly,  "Proc.  Roy.  Soc.,"  B,  79,  1907,  and  Marshall 
and  Jolly,  "Roy.  Soc.  Edinb.,"  45,  589,  1907. 

t  Marshall  and  Jolly,  "Philosophical  Transactions,  Royal  Society," 
London,  1905,  B.  cxcviii.,  99;  also  Marshall  and  Runciman,  "Journal  of 
Physiology,"  49,  17,  1914. 


988  THE    PHYSIOLOGY    OF    REPRODUCTION. 

swelling  and  congestion  of  the  membrane  constitute  a  prepara- 
tion for  the  reception  of  the  fertilized  ovum.  If  the  ovum  fails  of 
fertilization,  then  degenerative  changes  ensue,  and  the  membrane 
or  a  portion  of  it  is  cast  off  in  the  menstral  flow,  while  the  re- 
mainder is  absorbed.  According  to  this  view,  menstruation  is  an 
indication  that  fertilization  has  not  taken  place.*  This  view 
falls  in  with  the  belief  that  ovulation  normally  precedes  menstrua- 
tion by  a  considerable  interval.  A  modification  or  extension  of 
this  general  hypothesis  is  proposed  by  Bryce  and  Teacher. f 
They  believe  that  the  process  of  menstruation  is  a  cyclic  one, 
which  has  for  its  object  the  preparation  of  the  endometrium  for 
the  reception  of  the  ovum.  The  monthly  regeneration  keeps 
this  membrane  in  that  condition  of  youthful  irritability  which 
enables  it  to  respond  promptly  to  the  stimulus  of  the  ovum  by 
the  formation  of  a  decidua.  The  other  point  of  view  was  advo- 
cated especially  by  Pfluger  in  connection  with  his  theory  of  a 
common  cause  of  ovulation  and  menstruation.  He  assumed  that 
menstruation  occurs  before  the  ovum  reaches  the  uterus  and  that 
its  physiological  value  lies  in  the  fact  that  a  raw  surface  is  thus  made 
upon  which  the  ovum  is  grafted.  Menstruation,  according  to  him, 
is  an  operation  of  nature  for  the  grafting  of  the  fertilized  ovum 
upon  the  maternal  organism.  This  view  finds  considerable  support 
in  the  fact  that  in  some  of  the  lower  animals  (dogs)  the  flow  of 
blood  (prooestrum) '  precedes  fertilization. 

The  Effect  of  the  Menstrual  Cycle  on  Other  Functions.— It 
is  natural  to  suppose  that  such  marked  changes  as  occur  in  the 
ovary  and  uterus  during  the  menstrual  cycle  should  have  an  in- 
fluence upon  other  parts  of  the  body.  As  a  matter  of  fact,  it  is 
known  that  in  general  the  sense  of  well-being  varies  with  the  phases 
of  the  cycle.  At  the  time  of  or  in  the  period  just  preceding  the 
menstrual  flow  there  is  usually  a  more  or  less  marked  sense  of  ill- 
being  or  despondency,  and  a  diminution  in  general  efficiency. 
Efforts  have  been  made  to  explain  these  subjective  changes  gn  the 
assumption  that  the  body  processes  may  undergo  wave-like 
variations  corresponding  with  the  menstrual  cycle. J  The  numer- 
ous reports  made  prove  in  general  that  the  body  temperature  and 
pulse-rate  do  show  such  a  wave  moment,  reaching  a  maximum 
just  before  menstruation  and  falling  to  a  minimum  shortly  after 
menstruation.  The  changes,  however,  are  very  slight  and  hardly 

*  This  view  finds  expression  in  the  aphorisms:  "Women  menstruate 
because  they  do  not  conceive,"  Powers,  and  "The  menstrual  crisis  is  the 
physiological  homologue  of  parturition,"  Jacobi. 

f  Bryce  and  Teacher,  "Early  Development  and  Imbedding  of  the  Human 
Ovum,"  1908. 

J  Jacobi,  "Boylston  Prize  Essay — The  Question  of  Rest  for  Women 
during  Menstruation,"  1876. 


THE  FEMALE  REPRODUCTIVE  ORGANS.  989 

seem  to  be  sufficient  to  have  any  distinct  influence  on  the  body 
metabolism.  In  regard  to  blood-pressure  the  statement  is  fre- 
quently made  that  there  is  a  fall  at  or  during  the  menstrual  flow, 
but  some  observers  fail  to  get  this  result  and,  in  any  case,  it  is  not 
very  extensive.*  On  the  whole,  the  experimental  evidence  thus 
far  obtained  does  not  seem  to  indicate  any  very  significant  altera- 
tion in  the  bodily  functions  as  a  result  of  menstruation. 

The  Passage  of  the  Ovum  into  the  Uterus. — The  means  by 
which  the  ovum  gains  entrance  to  the  Fallopian  tubes  has  given 
rise  to  much  speculation  and  some  interesting  experiments.  It 
was  formerly  believed  (Haller)  that  at  the  time  of  ovulation  the 
fimbriated  end  of  the  Fallopian  tube  is  brought  against  the  ovary, 
the  movement  being  due  to  a  congestion  or  a  sort  of  erection  of  the 
fimbrise.  This  movement  has  not  been  observed,  and,  as  experi- 
ments show  that  small  objects  introduced  into  the  pelvic  cavity  are 
taken  up  by  the  tubes,  it  is  believed  that  the  cilia  upon  the  fimbrise 
and  in  the  tubes  may  suffice  to  set  up  a  current  that  is  sufficient 
to  direct  the  movements  of  the  ovum.  Attention  has  been  called 
to  the  fact  that  in  animals  with  a  bicornate  uterus  the  ova  may 
be  liberated  from  the  ovary  on  one  side,  as  shown  by  the  presence 
of  the  corpora  lutea,  while  the  embryos  are  developed  in  the  horn 
of  the  other  side.  As  further  evidence  for  the  same  possibility  of 
migration  it  has  been  shown  that  the  ovary  may  be  excised  on  one 
side  and  the  horn  of  the  uterus  on  the  other  and  yet  the  animal  may 
become  pregnant  after  sexual  union.  It  would  seem  probable, 
therefore,  that  the  ovum  is  discharged  into  the  pelvic  cavity  and 
may  be  caught  up  by  the  ciliary  movements  at  the  end  of  the  tube 
on  the  same  side,  or  may  traverse  the  pelvic  cavity  in  the  narrow 
spaces  between  the  viscera  and  be  received  by  the  tube  on  the 
other  side.  Such  a  view  explains  the  possible  occurrence  of  true 
abdominal  pregnancies,  and  suggests  also  the  possibility  that  ova 
may  at  times  fail  to  reach  the  uterus  at  all  and  may  undergo  de- 
struction and  absorption  in  the  abdominal  cavity.  In  some  of 
the  lower  animals — the  dog,  for  example — provision  is  made  for 
the  more  certain  entrance  of  the  ova  into  the  tubes  by  the  fact 
that  the  latter  end  in  connection  with  a  membranous  sac  of  peri- 
toneum which  envelopes  the  ovary.  The  sexual  fertilization  of  the 
ovum  is  supposed  to  take  place  shortly  after  its  entrance  into 
the  Fallopian  tube,  since  spermatozoa  have  been  found  in  this 
region,  and  the  fertilized  ovum,  before  reaching  the  seat  of  its  im- 
plantation in  the  body  of  the  uterus,  has  begun  its  development. 
By  the  act  of  coitus  the  spermatozoa  are  deposited  at  the  mouth 
of  the  uterus,  whence  they  make  their  way  toward  the  tubes, 

*  King,  "American  Journal  of  Physiology,"  34,  203,  1914;  also  Mosher, 
"Johns  Hopkins  Hospital  Bulletin,"  12,  178,  1901. 


990 


THE    PHYSIOLOGY    OF    REPRODUCTION. 


being  guided  in  their  movements  very  probably  by  the  opposing 
force  of  the  ciliary  contractions  in  the  uterus.  It  is  known  that 
the  cilia  of  the  tubes  and  uterus  contract  so  as  to  drive  inert 
objects  toward  the  vagina  and  they  carry  the  egg  in  this  direction, 
but  the  spermatozoa,  being  moved  by  the  contractions  of  their 
own  cilia  or  tails,  are  stimulated  to  advance  against  this  ciliary 
current.  The  act  of  fertilization  of  the  ovum  is  preceded  by 
certain  preparatory  changes  in  the  ovum  itself  which  are  described 
under  the  term  maturation. 

Maturation  of  the  Ovum. — The  process  of  maturation  occurs 
before  or  just  after  the  spermatozoon  enters  the  ovum.  At  the 
time  the  latter  is  extruded  from  the  follicle  it  is  a  single  cell  sur- 

rounded  by  a  layer  of  fol- 

ilcular  epithelium  forming 
the  corona  radiata,  which 
is  subsequently  lost.  The 
egg  proper  consists  of  cyto- 
plasm and  a  nucleus  or 
germinal  vesicle  containing 
a  nucleolus  or  germinal 
spot.  Within  the  cyto- 
plasm is  a  definite  collec- 
tion of  food  material  or 
yolk  which  is  sometimes 
designated  as  deutoplasm. 
The  whole  structure  is  sur- 
rounded by  a  membrane 
known  as  the  zona  radiata 
(Fig.  302).  Before  or  after 
the  egg  reaches  the  Fal- 
lopian tube  its  nucleus  undergoes  the  changes  preparatory  to 
a  mitotic  division.  The  changes  that  occur  in  an  ordinary  cell 
division  are  represented  schematically  in  Fig.  303.  The  nucleus 
at  first  presents  the  ordinary  chromatin  network,  and  in  the 
cytoplasm  lies  the  minute  structure  known  as  the  centrosome. 
This  latter  divides  into  two  daughter-centrosomes  (b)  which  move 
to  opposite  sides  of  the  nucleus  and  become  surrounded  by  rays, 
each  centrosome  with  its  radiating  system  forming  an  astro- 
sphere.  The  chromatin  material  in  the  nucleus  meanwhile  has 
collected  into  larger  threads  known  as  chromosomes  (c),  and 
the  nuclear  membrane  disappears  (d).  The  number  of  chromo- 
somes is  definite  for  each  species  of  animal.  The  chromosomes 
arrange  themselves  equatorially  between  the  astrospheres  and  then 
each  divides  longitudinally  into  two  parts  (/).  These  parts  migrate 
or  are  drawn  toward  their  respective  centrosomes  (g,  h,  i),  and  this 


Fig.  302. — Human  ovum  (Lee,  modified  from 
Nagel) :  n,  Nucleus  (germinal  vesicle)  containing 
tne  ameboid  nucleolus  (germinal  spot) ;  d,  deu- 
toplasmic  zone;  p,  protoplasmic  zone;  z,  zona 
radiata;  s,  perivitelhn  space. 


Fig.  303. — Schematic  representation    of    the   processes   occurring  during   cell    division, 

CBoveri.) 


THE  FEMALE  REPRODUCTIVE  ORGANS.  991 

division  is  followed  by  a  separation  of  the  cytoplasm  into  two 
parts.  Thus,  two  daughter-cells  are  formed,  each  containing  the 
same  number  of  chromosomes  as  the  parent  cell,  but  only  half  the 
amount  of  chromatin  material.  In  ordinary  cell  division  the 
chromosomes  again  form  a  resting  reticulum  and  a  nuclear 
membrane,  and  the  chromatin  substance  increases  in  quantity. 
The  primitive  egg-cells,  or  oogonia,  divide  according  to  this 
schema,  but  before  an  ovum  is  ready  for  fertilization  it  undergoes 
a  process  of  maturation  which  consists  in  two  successive  cell 
divisions  differing  somewhat  from  the  type  just  described.  Pre- 
ceding the  first  of  these  divisions  the  various  chromosomes  come 
together  in  pairs  and  fuse  more  or  less  completely,  the  process  of 
conjugation  being  designated  as  the  period  of  synapsis.  The 
evidence  indicates  that  in  this  pairing  of  the  chromosomes  one  of 
each  pair  was  originally  maternal  in  its  origin,  the  other  was 
paternal.  The  result  of  the  conjugation  is  to  reduce  the  number 
of  chromosomes  typical  for  the  species  by  one-half.  In  man,  for 
example,  the  typical  number  of  chromosomes  for  the  tissue  cells 
is  48;  by  the  synapsis  they  are  reduced  to  24.  Following  the 
synapsis  the  ovum  undergoes  the  first  of  the  maturation  divisions, 
sometimes  known  as  the  reduction  division.  The  two  ova  pro- 
duced are  very  unequal  in  size;  the  smaller  one  is  known  as  the 
first  polar  body,  and  it  subsequently  degenerates.  The  larger 
one  is  the  ovum,  but  it  now  contains  only  half  the  typical  number 
of  chromosomes,  since  in  the  division  the  paired  chromosomes 
separate,  one  of  each  pair  going  to  the  polar  body.  The  separation 
of  the  paired  chromosomes  is  such  that  the  ovum  gets  some  that 
were  of  maternal  and  some  that  were  of  paternal  origin.  After 
the  formation  of  the  first  polar  body  the  ovum  again  divides,  this 
time  in  a  typical  way,  with  an  equal  splitting  of  the  chromosomes, 
except  that  again  there  is  a  great  disparity  in  size,  the  smaller 
cell  being  known  as  the  second  polar  body.*  Since  the  first 
polar  body  after  its  separation  may  again  divide  into  two  cells, 
the  process  of  maturation  results  in  the  formation  of  four  cells, 
three  of  which  are  polar  bodies  and  may  be  regarded  as  abortive 
ova.  The  fourth,  the  matured  ovum,  retains  practically  all  of 
the  original  cytoplasm,  but  has  lost  a  part  of  its  chromatin  mate- 
rial and,  according  to  Boveri,  also  its  centrosome.  The  production 
of  these  four  cells  may  be  represented,  therefore,  by  a  schema  of 
the  kind  shown  in  Fig.  304. 

From  a  biological  standpoint  the  reduction  of  chromosomes 
throws  much  light  upon  the  significance  of  fertilization  by  the  male 
cell.  The  spermatozoon  before  it  is  ripe  undergoes  a  process  of 

*  Wilson,  "The  Cell  in  Inheritance  and  Development,"  also  Conklin, 
"Heredity  and  Environment,"  1914. 


I 
992  THE    PHYSIOLOGY    OF    REPRODUCTION. 

maturation  essentially  similar  to  that  described  for  the  ovum. 
Two  cell  divisions  take  place  with  the  formation  of  four  spermato- 
zoa, each  of  which,  however,  is  a  functional  spermatozoon.  In  the. 
process  of  division  the  number  of  chromosomes  in  each  cell  is 
reduced  to  half — part  of  maternal  and  part  of  paternal  origin. 
When  the  matured  ovum  and  the  matured  spermatozoon  fuse, 
therefore,  each  brings  half  the  normal  number  of  chromosomes, 
and  the  resulting  fertilized  ovum  is  a  cell  with  its  chromosomes 
restored  to  their  usual  number.  The  chromosomes  are  believed  to 
contain  the  material  which  conveys  hereditary  characteristics. 
The  chromosomes  of  maternal  origin  contain  carriers  of  charac- 
teristics belonging  to  the  stock  of  the  mother,  and  the  paternal 
chromosomes  the  carriers  for  the  qualities  transmitted  through 
the  paternal  side.  The  process  which  causes  each  element  to  lose 
a  part  of  this  material  before  its  union  with  the  cell  of  the  oppo- 


— Ovarian  egg. 


polar  body. 
Second  polar  body  (abortive  ovum). 
Fig.  304. — Schema  to  indicate  the  process  of  maturation  of  the  ovum. — (Boveri.) 

site  sex. is,  from  this  standpoint,  a  provision  by  means  of  which 
the  fertilized  egg,  from  which  the  offspring  develops,  shall  inherit 
the  characteristics  of  the  stock  to  which  each  parent  belongs, 
without  increase  in  the  typical  number  of  the  chromosomes.* 

Fertilization  of  the  Ovum. — The  spermatozoon  comes  into 
contact  with  the  ovum  probably  at  the  beginning  of  the  Fallopian 
tubes.  The  meeting  of  the  two  cells  is  possibly  not  simply  a  matter 
of  accidental  contact,  although  the  number  of  spermatozoa  dis- 
charged by  the  male  at  coitus  is  so  great  that  there  would  seem 
to  be  little  chance  for  the  ovum  to  fail  to  meet  some  of  them.  Ex- 
periments upon  the  reproductive  elements  of  plants  indicate,  how- 
ever, that  the  egg  may  contain  substances  which  serve  to  attract 
the  spermatozoon,  within  a  certain  radius,  by  that  force  which 
is  described  under  the  name  of  chemotaxis.  However  this  may  be, 
the  egg  unites  with  a  spermatozoon  and  under  normal  conditions 
with  only  one.  A  number  of  the  spermatozoa  may  penetrate 

*  For  a  popular  presentation  see  Boveri,  "Das  Problem  der  Befruchtung," 
Jena,  1902,  and  Conklin,  loc.  cit. 


Fig.  305. — Schematic  representation  of  the  processes  occurring  during  the  fertiliza- 
tion and  subsequent  segmentation  of  the  ovum. — (Boveri.)  The  chromatin  (chromo- 
somes) of  the  ovum  is  represented  in  blue,  that  of  the  spermatozoon  in  red. 


THE  FEMALE  REPRODUCTIVE  ORGANS.  993 

the  zona  radiata,  but  so  soon  as  one  has  come  into  contact  with 
the  cytoplasm  of  the  egg  a  reaction  ensues  in  the  surface  layer 
which  makes  it  impervious  to  other  spermatozoa.  The  spermato- 
zoon consists  of  three  essential  parts, — the  head,  the  middle  piece, 
and  the  tail.  The  last  named  is  the  organ  of  locomotion,  and 
after  the  spermatozoon  enters  the  egg  this  portion  atrophies  and 
disappears,  probably  by  absorption.  The  head  of  the  spermato- 
zoon represents  the  nucleus,  and  contains  the  valuable  chromatin 
material.  On  entering  the  egg  it  moves  toward  the  nucleus  of  the 
latter,  meanwhile  enlarging  and  taking  on  the  character  of  a  nu- 
cleus. The  egg  now  contains  two  nuclei, — one  belonging  to  it  origi- 
nally, the  female  pronucleus;  one  brought  into  it  by  the  sperma- 
tozoon, the  male  pronucleus.  The  two  come  together  and  fuse, 
— superficially  at  least, — forming  the  nucleus  of  the  fertilized  egg,  or 
the  segmentation  nucleus.  The  middle  piece  of  the  spermatozoon 
also  enters  the  egg,  but  its  exact  function  and  fate  is  still  a  matter 
of  uncertainty.  Boveri  believes  that  it  brings  into  the  egg  a 
centrosome  or  material  which  induces  the  formation  of  a  centro- 
some  in  the  ovum,  and  is,  therefore,  of  the  greatest  importance  in 
initiating  the  actual  process  of  cell  division  which  begins  promptly 
after  the  fusion  of  the  nuclei.  In  the  segmentation  nucleus  the  nor- 
mal number  of  chromosomes  is  restored,  and  it  is  believed  that  in 
the  subsequent  divisions  of  the  cell  to  form  the  embryo  the  chromo- 
somes are  so  divided  that  each  cell  gets  an  equal  division  of  mater- 
nal and  paternal  chromosomes,  and  thus  shares  the  hereditary 
characteristics  of  each  parental  stock.  This  view  is  represented  in  a 
schematic  way  by  Fig.  305,  taken  from  Boveri,  the  maternal  and 
paternal  chromosomes  being  indicated  by  different  colors.  Accord- 
ing to  this  description,  both  egg  and  spermatozoon  are  incomplete 
cells  before  fusion.  The  egg  contains  a  nucleus  and  a  large  cell 
body,  cytoplasm,  rich  in  nutritive  material,  but  it  lacks  a  centro- 
some or  the  conditions  necessary  for  the  formation  of  an  astro- 
sphere,  so  that  it  cannot  multiply.  The  spermatozoon  has  also 
chromatin  for  a  nucleus,  and  a  centrosome  or  the  material  which 
may  give  rise  to  a  centrosome,  but  it  lacks  cytoplasm — that  is, 
food  material  for  growth.  It  would  seem  that  if  the  spermatozoon 
could  be  given  a  quantity  of  cytoplasm  it  would  proceed  to  develop 
an  embryo  without  the  aid  of  an  ovum.  This  experiment  has,  in 
fact,  been  made  by  Boveri.  Eggs  of  the  sea-urchin  were  shaken 
violently  so  as  to  break  them  into  fragments.  If  now  a  spermato- 
zoon entered  one  of  these  fragments,  which  consisted  only  of  cyto- 
plasm, cell  multiplication  began  and  proceeded  to  the  formation 
of  a  larva.  On  the  other  hand,  it  would  seem  to  be  equally  evi- 
dent that  if  a  centrosome  was  present  in  the  egg  or  some  in- 
fluence could  be  brought  to  bear  upon  it  to  initiate  the  process  of 
63 


994  THE    PHYSIOLOGY    OF    REPRODUCTION. 

cell  division,  it  would  develop  without  a  spermatozoon.  In  some 
animals  eggs  do  normally  develop  at  times  without  fertilization 
by  a  spermatozoon  (parthenogenesis),  the  eggs  that  have  this 
property  probably  preserving  their  centrosomes.  Loeb*  has 
shown,  however,  in  some  most  interesting  experiments  that 
certain  eggs,  especially  those  of  the  sea-urchin  (Strongylocentro- 
tus  purpuratus),  which  normally  develop  by  fertilization  with 
spermatozoa,  may  be  made  to  develop  by  physicochemical  means. 
Numerous  means  for  bringing  about  artificial  fertilization  have 
been  described.  One  method  is  to  treat  the  egg  for  a  minute  or  two 
with  an  acid  (acetic,  formic,  etc.),  which  causes  the  formation  of  a 
membrane.  They  are  then  placed  for  a  certain  interval  in  a  hyper- 
tonic  sea  water,  made  by  adding  sodium  chlorid  to  ordinary  sea 
water.  They  are  then  transferred  to  normal  sea  water  and  after 
an  hour  or  so  they  begin  to  multiply  and  eventually  develop  into 
normal  larvae.  Similar  although  less  complete  results  were  ob- 
tained previously  by  Morgan.  Experiments  of  this  character 
would  indicate  that  the  spermatozoon  brings  into  the  ovum 
definite  substances,  which,  by  chemical  or  physicochemical  means, 
initiate  and  control  the  process  of  segmentation.  Suggestions  as 
to  the  nature  of  these  substances  are  at  present  very  hypothetical. 
Robertson  f  states  that  he  is  able  to  isolate  from  spermatozoa  a 
substance  which  can  fertilize  the  ovum,  that  is,  cause  the  forma- 
tion of  a  fertilization  membrane.  The  substance  is  not  defined 
chemically,  otherwise  than  to  state  that  it  is  not  a  protein  nor  an 
enzyme.  He  proposes  for  it  the  name  oocytin.  On  the  other  hand, 
F.  R.  LillieJ  claims  that  fertilization  is  due  to  a  substance  produced 
in  the  egg  itself — designated  as  fertilizin — which  acts  as  an  ambo- 
ceptor  binding  the  sperm  by  a  spermophile  group.  He  conceives 
that  the  sperm  when  thus  bound  activates  the  ovophile  side  chain 
in  the  fertilizin,  which  then  causes  fertilization.  According  to  this 
view  the  egg  is  really  self-fertilizing,  the  spermatozoon  furnishing 
simply  an  activating  substance,  and  the  function  of  the  sperm  can 
be  assumed  by  the  above-mentioned  reagents  which  induce  arti- 
ficial fertilization. 

Implantation  of  the  Ovum. — After  fertilization  in  the  tube  the 
ovum  begins  to  segment  and  multiply,  and  meanwhile  is  carried 
toward  the  uterus,  probably  by  the  action  of  the  cilia  lining  the  tube. 
Upon  reaching  the  cavity  of  the  uterus  it  becomes  attached  to  the 
mucous  membrane,  usually  in  the  neighborhood  of  the  fundus. 
The  membrane  of  the  uterus  has  become  much  thickened  mean- 
while, and  in  this  condition  is  known  usually  as  the  decidua.  The 

*Loeb,  "University  of  California  Publications,"  2,  pp.  83,  89,  and  113, 
1905.     See  also  Wilson,  "Archiv.  f.  entwick.  Mechanik,"  12,  1901. 
t  Robertson,  "Journal  of  Biological  Chemistry,"  12,  163,  1912. 
JF.  R.  Lillie,  "Science,"  October,  1913. 


THE    FEMALE    REPRODUCTIVE    ORGANS.  995 

portion  to  which  the  egg  becomes  attached  is  the  decidua  serotina, 
and  it  eventually  develops  into  the  placenta,  the  organ  through 
which  the  maternal  nutriment  is  supplied  to  the  fetus.  The  ovum 
has  made  considerable  progress  in  its  development  before  reaching 
the  uterus,  having  formed  amnion  and  chorion,  with  chorionic  villi. 
Some  of  the  ectodermal  cells  in  the  chorion  become  specialized  to 
form  a  group  of  trophoblastic  cells  which  have  a  digestive  action, 
and  it  is  suggested  that  the  activity  of  these  cells  enables  the  ovum 
to  become  attached  to  the  decidual  membrane  and  to  hollow  out 
spaces  in  which  the  chorionic  papilla  become  inserted.*  The  further 
development  of  the  egg  into  a  fetus,  the  formation  of  the  decidua 
graviditatis,  and  the  placenta  are  anatomical  features  that  need 
not  be  described  here.  Details  of  these  structures  will  be  found 
in  works  on  anatomy,  embryology,  or  obstetrics.  On  the  phys- 
iological side  it  has  been  found  that  removal  of  the  ovaries,  or  even 
destruction  of  the  corpora  lutea,  shortly  after  pregnancy  has  begun 
brings  the  process  to  an  end,  while  a  similar  operation  later  in 
pregnancy  has  no  effect  upon  the  developing  fetus  or  the  subsequent 
act  of  parturition.  It  seems,  therefore,  that  the  process  of  implan- 
tation of  the  ovum  in  the  uterine  mucous  membrane  and  the  devel- 
opment of  a  placenta  are  dependent  in  some  way  upon  the  ovaries. 
The  apparent  explanation  of  the  connection  is  given  in  the  hypothe- 
sis that  the  corpora  lutea,  during  their  rapid  development  at  the 
beginning  of  pregnancy,  give  off  an  internal  secretion  which  controls 
or  influences  in  some  essential  way  the  processes  connected  with 
the  fixing  of  the  fertilized  ovum.f 

The  Nutrition  of  the  Embryo — Physiology  of  the  Placenta. 
^— At  the  time  of  fertilization  the  ovum  contains  a  small  amount 
of  nutriment  in  its  cytoplasm.  The  amount,  however,  in  the  mam- 
malian ovum  is  small  and  suffices  probably  only  for  the  initial  stages 
of  growth.  When  the  ovum  becomes  implanted  in  the  decidual 
membrane  of  the  uterus  the  new  material  for  growth  must  be  ab- 
sorbed directly  from  the  maternal  blood  of  the  uterus.  Within 
a  short  time,  however,  the  ehorionic  villi  begin  to  burrow  into  the 
uterine  membrane  at  the  point  of  attachment,  the  decidua  serotina, 
and  the  placenta  gradually  forms  as  a  definite  organ  for  the  control 
of  fetal  nutrition.  The  details  of  histological  structure  of  this 
organ  must  be  obtained  from  anatomical  sources.  For  the  purposes 
of  understanding  its  general  functions  it  is  sufficient  to  recall  that 
the  placenta  consists  essentially  of  vascular  chorionic  papillae  from 
the  fetus  bathed  in  large  blood-spaces  in  the  decidual  membrane  of 
the  mother.  The  fetal  and  the  maternal  blood  do  not  come  into 
actual  contact;  they  are  separated  from  each  other  by  the  walls  of 

*  See  Minot,  "Transactions  of  the  American  Gynecological  Society,"  1904. 
t  Marshall  and  Jolly  and  Fraenkel,  loc.  tit. 


996  THE    PHYSIOLOGY    OF    REPRODUCTION. 

the  fetal  blood-vessels  and  the  epithelial  layers  of  the  chorionic  villi, 
but  an  active  diffusion  relation  is  set  up  between  them.  Nutritive 
material,  protein,  fat,  and  carbohydrate,  and  oxygen  pass  from 
the  maternal  to  the  fetal  blood,  and  the  waste  products  of  fetal 
metabolism — carbon  dioxid,  nitrogenous  wastes,  etc.,  pass  from  the 
fetal  to  the  maternal  blood.  The  nutrition  of  the  fetal  tissues  is 
maintained,  in  fact,  in  much  the  same  way  as  though  it  were  an 
actual  part  of  the  maternal  organism.  That  material  passes  from 
the  maternal  to  the  fetal  blood  is  a  necessary  inference  from  the 
growth  of  the  fetus.  The  fact  has  also  been  demonstrated  repeat- 
edly by  direct  experiment.  Madder  added  to  the  food  of  the  mother 
colors  the  bones  of  the  embryo.  Salts  of  various  kinds,  sugar,  drugs, 
etc.,  injected  into  the  maternal  circulation  may  afterward  be  de- 
tected in  the  fetal  blood.  But  we  are  far  from  having  data  that 
would  justify  us  in  supposing  that  the  exchange  between  the 
two  bloods  is  effected  by  the  known  physical  processes  of  os* 
mosis,  diffusion,  and  filtration.  The  difficulties  in  understanding 
the  exchange  in  this  case  are  the  same  as  in  the  absorption  of  nour- 
ishment by  the  tissues  generally.  It  is  perhaps  generally  assumed 
that  the  chorionic  villi  play  an  active  part  in  the  process,  func- 
tioning, in  fact,  in  much  the  same  way  as  the  intestinal  villi.  This 
assumption  implies  that  the  epithelial  cells  of  the  villi  take  an  active 
part  in  the  absorption  of  material  by  virtue  of  processes  which  can- 
not be  wholly  explained,  but  which  without  doubt  are  due  to  the 
chemical  and  physical  properties  of  the  substance  of  which  they  are 
composed.  This  assumption  does  not  mean  that  the  simpler 
and  better  understood  physical  properties  of  diffusion  and  osmosis 
are  not  also  important.  The  respiratory  exchange  of  gases,  the 
diffusion  of  water,  salts,  and  sugar,  may  be  largely  controlled  in  this 
way.  There  are  no  facts  at  least  which  contradict  such  an  assump- 
tion. The  passage  of  fats  and  proteins,  however,  would  seem  to 
require  some  special  activity  in  the  chorionic  tissue,  which  may  be 
connected  with  the  presence  of  special  enzymes.  Glycogen  occurs 
in  the  placenta  itself  and  in  all  the  tissues  of  the  embryo  during  the 
period  of  most  active  growth.  In  the  later  period  of  embryonic 
life,  as  the  liver  assumes  its  functions,  the  glycogen  becomes 
more  localized  to  this  organ  and  disappears,  except  for  traces, 
in  the  skin,  lungs,  and  other  tissues  in  which  it  was  present  at 
first  in  considerable  quantities.  It  would  appear,  therefore,  that 
glycogen  (sugar)  represents  one  of  the  important  materials  for  the 
growth  of  the  embryo,  and  that  in  the  beginning  at  least  the  tissues 
generally  have  a  glycogenetic  power.  The  sugar  brought  to  the 
placenta  in  the  maternal  blood  passes  over  into  the  fetal  blood  and 
the  excess  beyond  that  immediately  consumed  is  deposited  in  the 
tissues  as  glycogen.  The  body  fat  of  the  fetus  is  at  first  slight  in 


THE    FEMALE    REPRODUCTIVE    ORGANS.  997 

amount,  but  after  the  sixth  month  begins  to  increase  with  some 
rapidity.  The  fat-forming  tissues  are  in  full  activity,  therefore, 
before  birth,  and  function  doubtless  in  the  same  way  as  in 
the  adult.  Before  birth  also  the  various  organs  begin  to  take  on 
their  normal  activity.  The  kidney  may  form  urine  long  before 
birth,  as  is  shown  by  the  presence  of  this  secretion  in  the  bladder, 
and,  shortly  before  birth  at  least,  it  has  the  power  of  producing 
hippuric  acid,  as  may  be  shown  by  injecting  benzoates  into  the 
blood  of  the  mother.  The  kidney  functions  of  the  embryo,  how- 
ever, are  doubtless  performed  chiefly  by  the  placenta  and  the 
kidney  of  the  mother  up  to  the  time  of  birth.  That  the  liver  also 
begins  to  assume  its  functions  early  is  shown  by  the  fact  that  from 
the  fifth  to  the  sixth  month  one  may  find  bile  in  the  gall-bladder. 
In  the  intestine,  colon,  there  is  found  also  a  collection  of  excrement, 
the  meconium,  which  shows  that  the  motor  and  secretory  functions 
of  the  intestinal  canal  may  be  present  in  the  last  months  of  fetal 
life.  From  the  pancreas  a  proteolytic  enzyme  may  be  extracted  at 
the  time  of  birth  or  before,  but  the  amylolytic  enzyme  is  not  formed 
apparently  until  some  time  later.  It  is  stated,  at  least,  that  it  is 
not  present  at  birth.  In  general,  it  is  evident  that  for  a  long  period 
the  maternal  organism  digests  and  prepares  the  food  for  the  embryOj 
excretes  the  wastes,  regulates  the  conditions  of  temperature,  etc., 
as  it  does  for  a  portion  of  its  own  substance,  but  as  the  fetus  ap- 
proaches term  its  tissues  and  organs  begin  to  assume  more  of  an 
independent  activity,  as  indeed  must  be  the  case  in  preparation 
for  the  sudden  change  at  birth.  In  this  respect,  as  in  all  parts  of 
the  reproductive  process,  we  meet  with  regulations  whose  mechanism 
is  but  dimly  understood. 

Changes  in  the  Maternal  Organism  during  Pregnancy. — 
The  two  most  distinct  effects  upon  the  mother  that  result  from 
pregnancy  are  the  growth  of  the  uterus  and  of  the  mammary  gland. 
The  virgin  uterus  is  small  and  firm,  weighing  from  30  to  40  gms., 
while  at  the  end  of  pregnancy  it  may  weigh  as  much  as  1000  gms. 
This  great  increase  in  material  is  due  partly  to  the  growth  of  new 
muscular  tissue  and  partly  to  an  hypertrophy  of  the  muscle  already 
present.  In  the  uterus  at  term  the  muscle  cells  are  much  longer 
and  larger  than  in  the  organ  before  the  implantation  of  the 
fertilized  ovum.  The  stimulus  that  initiates  and  controls  this 
new  growth  is  seemingly  the  fertilized  ovum  itself,  but  the  phys- 
iological means  employed  are  not  comprehended.  We  know 
from  experiments  upon  lower  animals  (Rein)  that  when  all 
connections  with  the  central  nervous  system  are  severed  the 
fetus  develops  normally  and  the  uterus  increases  correspond- 
ingly in  size  and  weight.  The  influence  of  the  ovum  on  the 
uterus  must  be  exerted,  therefore,  in  all  probability,  through 
some  chemical  stimulus  which  it  gives  to  the  organ.  The  effect 


998  THE    PHYSIOLOGY    OF    REPRODUCTION. 

of  the  presence  and  growth  of  the  fetus  on  the  mammary 
gland  is  treated  in  a  separate  paragraph  below.  In  addition  to 
these  two  visible  effects  it  is  evident  that  the  growth  of  the  fetus 
has  an  important  influence  on  general  metabolism  and  therefore 
upon  the  whole  maternal  organism.  This  fact  is  indicated  by  the 
marked  changes  often  exhibited  in  the  physical  and  mental  con- 
dition of  the  mother.  It  is  shown  more  precisely  by  a  study  of  the 
nutritional  changes.  Numerous  investigations  have  been  made 
upon  this  subject,  especially  as  regards  the  nitrogen  equilibrium. 
During  the  latter  part  of  pregnancy,  especially,  the  nitrogen  balance 
is  positive — that  is,  nitrogen  is  stored  as  protein — due  doubtless 
both  to  the  growth  of  the  embryo  and  the  increase  in  material  in 
the  uterus  and  mammary  gland.  The  proportion  of  ammonia  in 
the  urine  increases  during  pregnancy  and  especially  during  labor. 
Parturition. — The  fetus  "  comes  to  term  "  usually  in  the  tenth 
menstrual  period  after  conception — that  is,  about  280  days  after 
the  last  menstruation.  The  actual  time  of  delivery,  however, 
shows  considerable  variation.  Delivery  occurs  in  consequence  of 
contractions,  more  or  less  periodical,  of  the  musculature  of  the 
uterus,  and  reflex  as  well  as  voluntary  contractions  of  the  abdom- 
inal muscles.  It  has  been  shown  that  delivery  may  occur  when  the 
nerves  connecting  the  uterus  with  the  central  nervous  system  are 
severed,  so  that  the  act  is  essentially  an  independent  function  of 
the  uterus,  although  under  normal  conditions  the  contractions  of 
this  organ  are  doubtless  influenced  by  reflex  effects  through  its 
extrinsic  nerves.  It  has  been  shown  that  contractions  of  the  gravid 
uterus  may  be  caused  by  stimulation  of  various  sensory  nerves,  and 
in  women  it  is  known  that  delivery  may  be  precipitated  prematurely . 
by  various  mental  or  physical  disturbances.  The  interesting  prob- 
lem physiologically  is  to  determine  the  normal  factor  or  factors  that 
bring  on  uterine  contractions  at  term.  Various  more  or  less  unsatis- 
factory theories  have  been  proposed.  Some  authors  attribute 
the  act  to  a  change  in  the  maternal  organism,  such  as  mechani- 
cal distension  of  the  uterus,  a  venous  condition  of  the  blood,  a 
degenerative  change  in  the  placenta,  etc.,  while  others  suppose  that 
the  initial  stimulus  comes  from  the  fetus.  In  the  latter  case  it 
is  suggested  that  the  increasing  metabolism  of  the  fetus  is  insuffi- 
ciently provided  for  by  the  placental  exchange,  and  that  therefore 
certain  products  are  formed  which  serve  to  stimulate  the  uterus 
to  contraction.  Healy  and  Kastle*  suggest  another  hypothesis  for 
which  they  give  some  experimental  support.  They  believe  that  a 
hormone  is  formed  in  the  mammary  gland,  which  at  this  time  takes 
on  an  accelerated  development,  and  this  hormone  by  a  stimulating 
effect  on  the  uterus  initiates  normal  labor. 

*  Healy  and  Kastle,  "Bulletin  160,  Ky.  Agricultural  Exp.  Station,"  1912. 


THE  FEMALE  REPRODUCTIVE  ORGANS.  999 

The  duration  of  the  labor  pains  is  variable,  but  usually  they  are 
longer  in  primiparae  *en  to  twenty  hours  or  more,  than  in  multip- 
arse.  After  the  fetus  is  delivered  the  contractions  of  the  uterus 
continue  until  the  placenta  also  is  expelled  as  the  "after-birth." 
During  these  latter  contractions  the  fetal  blood  in  the  placenta  is, 
for  the  most  part,  squeezed  into  the  circulation  of  the  newborn 
child.  The  hemorrhage  from  the  walls  of  the  uterus  due  to  the  rup- 
ture of  the  placenta  may  be  profuse  at  first,  but  under  normal  con- 
ditions is  soon  controlled  by  the  firm  contraction  of  the  uterine  walls. 

The  Mammary  Glands. — At  the  time  of  puberty  the  mam- 
mary glands  increase  in  size,  but  this  growth  is  confined  largely 
to  the  connective  tissue;  the  true  glandular  tissue  remains  rudi- 
mentary and  functionless.  There  is  reason  to  believe  that  the 
growth  of  the  gland  in  the  prepubertal  period,  like  other  secondary 
sexual  characteristics,  is  controlled  by  an  internal  secretion  from 
the  interstitial  tissue  of  the  ovaries  (p.  893).  At  the  time  of  con- 
ception the  glandular  tissue  is  in  some  way  stimulated  to  further 
growth.  Secreting  alveoli  are  formed,  and  during  the  latter  part 
of  pregnancy  they  produce  an  incomplete  secretion,  scanty  in 
amount,  known  as  colostrum.  After  delivery  the  gland  evidently 
is  again  brought  under  the  influence  of  special  stimuli.  It  becomes 
rapidly  enlarged  and  a  more  abundant  secretion  is  formed.  For  the 
first  day  or  two  this  secretion  still  has  the  characteristics  of  colos- 
trum, but  on  the  third  or  fourth  day  the  true  milk  is  formed  and 
thereafter  is  produced  abundantly,  during  the  period  of  lactation, 
under  the  influence  of  the  act  of  milking.  If  during  this  period  a 
new  conception  occurs,  the  milk  secretion  is  altered  in  composition 
and  finally  ceases.  On  the  other  hand,  if  the  act  of  nursing  is  aban- 
doned permanently  the  glands  after  a  preliminary  stage  of  turgid- 
ity  undergo  retrogressive  changes  that  result  in  the  cessation  of 
secretory  activity.  The  colostrum  secretion  that  occurs  during 
pregnancy  and  for  a  day  or  two  after  birth  differs  from  milk  in 
its  composition  and  histological  structure.  It  is  a  thin,  yellowish 
liquid  containing  a  larger  percentage  of  albumin  and  globulin 
and  a  smaller  percentage  of  milk-sugar  and  fat  than  normal  milk. 
Under  the  microscope  it  shows,  in  addition  to  some  fat  droplets, 
certain  large  elements, — the  colostrum  corpuscles.  These  con- 
sist of  spherical  cells  filled  with  fat  droplets,  and  are  most  probably 
leucocytes  filled  with  fat  which  they  have  ingested.  Colostrum 
corpuscles  may  occur  in  milk  whenever  the  secretion  of  the  gland 
is  interfered  with,  and  their  presence  may  be  taken  as  an  indi- 
cation of  an  incomplete  secretion. 

Conditions  Controlling  the  Secretion  of  the  Mammary  Gland. 
—The  physiological  connection  between  the  uterus  and  the 
mammary  gland  is  shown  by  the  facts  mentioned  in  the  pre- 


1000  THE    PHYSIOLOGY    OF    REPRODUCTION. 

ceding  paragraph.  That  the  ovary  also  shares  in  this  influence 
either  directly  or  through  its  effect  on  the  uterus  is  shown  by 
the  fact  that  after  complete  ovariotomy  the  mammary  gland  under- 
goes atrophy.  This  undoubted  influence  of  one  organ  upon  the 
other  might  be  exerted  either  through  the  central  nervous  sy&tem 
or  by  way  of  the  circulation.  There  are  indications  that  the 
secretion  of  the  mammary  glands  is  under  the  control,  to  some 
extent  at  least,  of  the  central  nervous  system.  For  instance,  in 
women  during  the  period  of  lactation  cases  have  been  recorded 
in  which  the  secretion  was  altered  or  perhaps  entirely  suppressed 
by  strong  emotions,  by  an  epileptic  attack,  etc.  This  indication 
has  not  received  satisfactory  confirmation  from  the  side  of  ex- 
perimental physiology.  Eckhard  found  that  section  of  the  main 
nerve-trunk  supplying  the  gland  in  goats,  the  external  spermatic, 
caused  no  difference  in  the  quantity  or  quality  of  the  secretion. 
Rohrig  obtained  more  positive  results,  inasmuch  as  he  found  that 
some  of  the  branches  of  the  external  spermatic  supply  vasomotor 
fibers  to  the  blood-vessels  of  the  gland  and  influence  the  secretion 
of  milk  by  controlling  the  local  blood-flow  in  the  gland.  Section 
of  the  inferior  branch  of  this  nerve,  for  example,  gave  increased 
secretion,  while  stimulation  caused  diminished  secretion,  as  in  the 
case  of  the  vasoconstrictor  fibers  to  the  kidney.  These  results 
have  not  been  confirmed  by  others — in  fact,  they  have  been  sub- 
jected to  adverse  criticism — and  they  cannot,  therefore,  be  ac- 
cepted unhesitatingly. 

After  apparently  complete  separation  of  the  gland  from  all  its 
extrinsic  nerves,  not  only  does  the  secretion,  if  it  was  previously 
present,  continue  to  form,  although  less  in  quantity,  but  in  opera- 
tions of  this  kind  upon  pregnant  animals  the  glands  increase  in  size 
during  pregnancy  and  become  functional  after  the  act  of  parturi- 
tion.* This  result  confirms  the  older  experiments  of  Goltz,  Rein, 
and  others,  according  to  which  section  of  all  the  nerves  going  to 
the  uterus  does  not  prevent  the  normal  effect  on  lactation  after 
delivery.  Regarding  the  question  of  the  existence  of  secretory 
nerves,  Baschf  reports  that  extirpation  of  the  celiac  ganglion  or 
section  of  the  spermatic  nerve  does  not  prevent  the  secretion,  but 
causes  the  appearance  of  colostrum  corpuscles. 

Experiments,  therefore,  as  far  as  they  have  been  carried  in- 
dicate that  the  gland  is  under  the  regulating  control  of  the  cen- 
tral nervous  system,  either  through  secretory  or  more  probably 
through  vasomotor  fibers.  The  bond  of  connection  between  the 
mammary  gland  and  the  uterus  is,  however,  established  mainly 

*  Mironow,  "Archives  des  sciences  biologiques,"  St.  Petersburg,  3,  353, 

1894 

t  Basch,  "Ergebnisse  der  Physiologic,"  vol.  ii.,  part  i,  1903. 


THE    FEMALE    REPRODUCTIVE    ORGANS.  1001 

through  the  blood  rather  than  through  the  nervous  system.  Some 
direct  evidence  for  this  point  of  view  is  furnished  by  the  interesting 
experiments  of  Starling  and  Lane-Claypon.*  These  authors  found 
that  extracts  made  from  the  body  of  the  fetus,  or  rather  from  the 
bodies  of  many  fetuses,  when  injected  repeatedly  into  a  virgin  rabbit 
caused  a  genuine  development  of  the  mammary  glands  closely 
simulating  the  growth  that  normally  occurs  during  pregnancy. 
Since  similar  extracts  made  from  ovaries,  placental  and  uterine 
tissues  had  no  effect,  they  conclude  that  a  specific  chemical  sub- 
stance (a  hormone)  is  produced  in  the  fetus  itself  and,  after  absorp- 
tion into  the  maternal  blood,  acts  upon  the  mammary  gland,  stim- 
ulating it  to  growth.  Since  the  birth  of  the  fetus  is  followed  by 
active  secretion  in  the  mammary  glands  they  adopt  further  the 
view  that  this  substance,  while  promoting  the  growth  of  the  gland 
tissue,  inhibits  the  catabolic  processes  which  lead  to  the  formation 
of  the  secretion.  With  the  birth  of  the  fetus  this  substance  is 
withdrawn  and  secretion  begins,  and,  on  the  contrary,  the  secretion 
is  suspended  when  a  new  pregnancy  is  well  advanced.  Further 
evidence  of  the  same  kind  is  furnished  by  the  interesting  case  of  the 
Blazek  sisters.f  These  twins  had  a  common  circulation  but  sepa- 
rate nervous  systems.  Pregnancy  and  parturition  in  one  was 
followed  by  a  secretion  of  the  mammary  glands  of  both. 

As  was  said  in  speaking  of  the  histology  of  the  gland,  the  se- 
creting alveoli  are  not  fully  formed  until  the  first  pregnancy.  Dur- 
ing the  period  of  gestation  the  epithelial  cells  multiply,  the  alveoli 
are  formed,  and  after  parturition  secretion  begins.  As  the  liquid 
is  formed  it  accumulates  in  the  enlarged  galactophorous  ducts,  and 
after  the  tension  has  reached  a  certain  point  further  secretion 
is  apparently  inhibited.  If  the  ducts  are  emptied,  by  the  infant 
or  otherwise,  a  new  secretion  begins.  The  emptying  of  the  ducts, 
in  fact,  seems  to  constitute  the  normal  physiological  stimulus  to 
the  gland-cells,  but  how  this  act  affects  the  secreting  cells,  whether 
reflexly  or  directly,  is  not  known. 

The  possibility  that  the  mammary  secretion  is  influenced  by 
various  internal  secretions  has  been  brought  out  by  the  experiments 
of  Ott  and  Scott  .J  These  observers  find  that  extracts  of  several 
glands,  particularly  of  the  posterior  lobe  of  the  hypophysis  and  of 
the  corpus  luteum,  have  a  distinct  stimulating  effect  upon  the 
mammary  gland.  Whether  or  not  this  influence  is  exerted  nor- 
mally remains  to  be  determined. 

Composition  of  the  Milk. — The  composition  of  milk  is  com- 

*  Lane-Claypon  and  Starling,  "Proceedings  of  the  Royal  Society,"  1906, 
B.  Ixxvii.;  see  also  Starling  in  "Lancet,"  1905. 

t  Basch,  "Deut.  Med.  Wochenschrift,"  36,  981,  1910. 

I  Ott  and  Scott,  "Therapeutic  Gazette,"  Oct.,  1911,  May  and  Nov.,  1912. 


1002  THE    PHYSIOLOGY    OF    REPRODUCTION. 

plex  and  variable.*  The  important  constituents  are  the  fats,  held 
in  emulsion  as  minute  oil  droplets,  and  consisting  chiefly  of  olein 
and  palmitin;  casein,  a  nucleo-albumin  which  clots  under  the  in- 
fluence of  rennin;  milk-albumin  or  lactalbumin,  a  protein  resem- 
bling serum-albumin;  lactoglobulin;  lactose  or  milk-sugar;  lecithin, 
cholesterin,  phosphocarnic  acid,  urea,  creatin,  citric  acid,  enzymes, 
and  mineral  salts.  It  is  well  known  also  that  many  foreign  sub- 
stances— drugs,  flavors,  etc. — introduced  with  the  food  are  secreted 
in  the  milk.  An  average  composition  is:  proteins,  2  to  3  per  cent.; 
fats,  3  to  4  per  cent.;  sugar,  6  to  7  per  cent.;  salts,  0.2  to  0.3  per 
cent.  The  fact  that  casein  and  milk-sugar  do  not  exist  preformed 
in  the  blood  is  an  argument  in  favor  of  the  view  that  they  are  formed 
by  the  secretory  metabolism  of  the  gland  cells.  The  special  com- 
position of  the  milk-fat  and  the  histological  appearance  of  the 
gland  cells  during  secretion  suggest  the  view  that  the  fat  is  also 
constructed  within  the  gland  itself.  Bunge  has  called  attention 
to  the  fact  that  the  inorganic  salts  of  milk  differ  quantitatively 
from  those  in  the  blood-plasma  and  resemble  closely  the  propor- 
tions found  in  the  body  of  the  young  animal,  thus  indicating  an 
adaptive  secretion.  This  fact  is  illustrated  in  the  following  table 
giving  the  mineral  constituents  in  100  parts  of  ash: 

YOUNG  PUP.     DOGS'  MILK.     DOGS'  SERUM. 

K2O..                       8.5  10.7  2.4 

Na20 8.2                  6.1  52.1 

CaO 35.8  34.4  2.1 

MgO 1.6                  1.5  0.5 

Fe2O, 0.34                0.14  0.12 

P,Ofi..                           39.8  37.5  5.9 

Cl... 7.3  12.4  47.6 

On  account  of  the  use  of  cows'  milk  in  place  of  human  milk  in 
the  nourishment  of  infants  much  attention  has  been  given  to 
the  relative  composition  and  properties  of  the  two  secretions. 
The  chief  difference  between  the  two  lies  apparently  in  the  casein. 
The  casein  of  human  milk  is  smaller  in  amount,  curdles  in  loosei 
flocks  than  that  of  cows'  milk,  and  seems  to  dissolve  more  easily 
and  completely  in  gastric  juice.  The  former  also  contains  rela- 
tively more  lecithin  and  less  ash,  particularly  the  lime  salts.  On 
the  other  hand,  cows'  milk  contains  less  sugar  and  fat.  In  using 
it,  therefore,  for  the  nutrition  of  infants  it  is  customary  to  add 
water  and  sugar.  The  composition  of  cows'  milk  is  so  well  known 
that  it  is  easy  to  modify  it  for  special  cases  according  to  the  in- 
dications. The  rules  for  this  procedure  will  be  found  in  works 
upon  pediatrics. 

*  For  data  as  to  composition  and  hygienic  relations,  see  Bulletin  41, 
"Hygienic  Laboratory,"  Public  Health  and  Marine  Hospital  Service,  U.  S., 
Washington,  1908. 


CHAPTER  LIH. 
PHYSIOLOGY  OF  THE  HALE  REPRODUCTIVE  ORGANS, 

Puberty. — The  sexual  life  of  the  male  is  longer  than  that  of  the 
female.  Puberty  or  sexual  maturity  begins  somewhat  later, — in 
temperate  climates  at  about  the  fifteenth  year;  but  there  is  no  dis- 
tinct limitation  of  the  reproductive  powers  in  old  age  correspond- 
ing to  the  menopause  of  the  female.  At  the  time  of  puberty  and 
for  a  short  preceding  period  the  boy  grows  more  rapidly  in  stature 
and  weight,  and  the  assumption  of  its  complete  functions  by  the 
testis  exerts  a  general  influence  upon  the  organism  as  a  whole. 
One  of  the  superficial  changes  at  this  period  which  is  very  evident 
is  the  alteration  in  pitch  of  the  voice.  Owing  to  the  rapid  growth 
of  the  larynx  and  the  vocal  cords  the  voice  becomes  markedly 
deeper,  and  the  change  is  in  some  cases  sufficiently  sudden  to  cause 
the  well-known  phenomenon  of  the  breaking  of  the  voice.  The 
neuromuscular  control  of  the  vocal  cords  becomes  for  a  time  un- 
certain. The  completion  of  puberty  can  not  be  determined  in  the 
boy  with  the  same  exactness  as  in  the  girl,  in  whom  menstruation 
furnishes  a  visible  sign  of  sexual  maturity.  Part  of  the  sexual 
mechanism  may  be  functional  long  before  the  time  of  puberty, 
as  is  shown  by  the  presence  of  sexual  desire  and  the  possibility 
of  erection;  but  fully  developed  spermatozoa  are  not  produced 
until  this  period,  and  indeed  the  presence  of  ripe  and  functional 
spermatozoa  in  the  testis  is  the  only  certain  sign  that  sexual  ma- 
turity has  been  attained.  Puberty  as  thus  defined  consists  in  the 
maturation  of  the  testis  in  the  male,  and  of  the  ovary  in  the  female. 

It  will  be  recalled  that  in  the  interesting  work  upon  the  internal 
secretion  of  the  testes  reported  by  Steinach  (p.  893),  he  empha- 
sizes the  fact  that  these  organs  consist  of  two  distinct  parts,  the 
reproductive  cells  proper  lining  the  seminiferous  tubules  and  the 
interstitial  tissue.  This  latter  tissue  forms  the  internal  secretion, 
which  is  responsible  in  all  probability  for  the  development  of  the 
secondary  sexual  characteristics,  such  as  the  enlargement  of  the 
penis  and  its  accessory  glands  (vesicles,  prostate),  the  appearance 
of  sexual  desire,  the  prepubertal  growth,  etc.  Since  the  full  devel- 
opment of  these  characteristics  marks  the  appearance  of  puberty, 
Steinach  proposes  to  designate  the  mass  of  interstitial  tissue  as  the 
"pubertal  gland."  Normally,  the  full  establishment  of  the  sex 

1003 


1004  THE    PHYSIOLOGY    OF    REPRODUCTION. 

characteristics  is  coincident  with  the  maturation  of  functional 
activity  in  the  generative  part  of  the  gland,  and  the  practical  indi- 
cation of  the  completion  of  puberty  is  the  formation  of  spermatozoa. 
In  Steinach's  experiments  these  two  functions  of  the  testis  were 
separated,  and  puberty,  so  far  as  the  development  of  sex  character- 
istics was  concerned,  was  established  without  the  production  of 
spermatozoa.  It  seems  probable  that  the  secretions  of  the  inter- 
stitial tissue  begin  to  influence  the  rest  of  the  organism  some  time 
before  the  generative  elements  mature,  since  sexual  appetite  may 
be  present  before  puberty,  and  the  prepubertal  growth  changes 
appear  gradually.  The  history  of  this  tissue,  moreover,  is  bound  up 
in  some  intimate  way  with  the  activity  of  other  glands  of  internal 
secretion,  with  the  thymus,  the  cortical  portion  of  the  adrenal 
gland,  and  particularly  with  the  pituitary  gland.  It  will  be  re- 
membered that  deficiency  of  the  pituitary  gland  (posterior  lobe)  is 
accompanied  by  a  condition  of  sexual  infantilism. 

The  Properties  of  the  Spermatozoa. — The  development  and 
maturation  of  the  spermatozoa  in  the  testis  has  been  followed 
successfully  by  histological  means.  The  mother-cells  of  the  sper- 
matozoa, the  spermatocytes,  give  rise  to  four  daughter-cells,  sper- 
matids,  each  of  which  develops  into  a  functional  spermatozoon. 
The  process  in  this  case  is  something  more  than  mere  cell  division, 
since  in  the  spermatozoa  eventually  produced  the  number  of 
chromosomes  present  in  the  nucleus — that  is,  the  head  of  the  sper- 
matozoon— are  reduced  by  one-half.  The  process  of  production 
of  the  spermatozoa  is  therefore  quite  analogous  to  the  maturation 
of  the  ovum  during  the  formation  of  the  polar  bodies.  The  forma- 
tion and  maturation  of  the  spermatozoa  may  be  represented  by 
a  schema  similar  to  that  used  in  the  case  of  the  ova,  as  follows  (Fig. 
306) :  In  the  case  of  the  ovum  four  ova  are  produced,  but  only  one 
is  functional,  and  this  one,  the  ripe  egg,  is  characterized  by  its  large 
amount  of  cytoplasm,  its  inability  to  undergo  further  cell  division 
until  fertilized,  and  the  reduction  of  its  chromosomes  to  half  the  num- 
ber characteristic  of  the  body  cells  of  the  species.  In  the  case 
of  the  spermatozoa,  the  four  cells  produced  are  all  functional,* 
and  are  characterized  by  the  practical  loss  of  cytoplasm,  reduc- 
tion of  chromosomes  by  one-half,  and  inability  to  multiply  until 
cell  material  is  furnished.  The  two  cells  supplement  each  other, 
therefore.  Their  union  restores  the  normal  number  of  chromo- 
somes, part  of  which  are  now  maternal  and  part  paternal;  the  egg 
supplies  the  cytoplasm  and  the  spermatozoon  nuclear  material  and 
the  definite  stimulus  that  leads  to  multiplication. 

*  It  is  an  interesting  fact  that  in  some  cases  (bees)  two  kinds  of  spermatids 
are  formed  by  an  unequal  division  of  the  spermatocyte,  and  the  smaller  of 
the  two  is  abortive,  as  in  the  case  of  the  polar  bodies  of  the  egg. 


THE  MALE  REPRODUCTIVE  ORGANS. 


1005 


Primary 
spermatocyte. 


Secondary 
spermatocytes 


Spermatids. 


Spermatozoa. 

Fig.  306. — Schema  to  indicate  the  proc- 
ess of  maturation  of  the  spermatozoa. — 
08  overi). 


The  spermatozoa  are  produced  in  enormous  numbers.  It  is 
calculated  that  at  ejaculation  each  cubic  centimeter  of  the  liquid 
contains  from  sixty  to  seventy 
millions  of  these  cells.  The 
adult  ripe  spermatozoon  is 
characterized  as  an  independ- 
ent cell  by  its  great  motility, 
due  to  the  cilia-like  contrac- 
tions of  its  tail.  Its  power  of 
movement  or  its  vitality  is 
retained  under  favorable  con- 
ditions for  very  long  periods. 
The  most  striking  instance  of 
this  fact  is  found  in  the  case 

of  bats.  In  these  animals  copulation  takes  place  in  the  fall  and 
the  uterus  of  the  female  retains  the  spermatozoa  in  activity  until 
the  period  of  ovulation  in  the  following  spring.  Even  in  the  human 
being  it  is  believed  that  the  spermatozoa  may  exist  for  many  days 
in  the  uterus  and  Fallopian  tubes  of  the  female.  In  the  semen  that 
is  ejaculated  during  coitus  the  spermatozoa  are  mixed  with  the 
secretions  of  the  accessory  reproductive  glands,  such  as  the  seminal 
vesicles,  the  prostate  gland,  and  Cowper's  gland.  The  specific  in- 
fluence of  each  of  these  secretions  is  not  entirely  understood,  but 
experiments  show  that  in  some  way  they  are  essential  to  or  aid 
greatly  in  maintaining  the  motility  of  the  spermatozoa.  Steinach  * 
has  found,  for  example,  that  removal  of  the  prostate  gland  and 
seminal  vesicles  in  white  rats  prevents  successful  fertilization  of  the 
female,  although  the  ability  and  desire  to  copulate  are  not  inter- 
fered with.  This  result  has  been  corroborated  by  Walker,  f  Accord- 
ing to  this  author,  removal  of  both  the  prostate  and  seminal  vesicles 
in  the  rat  leaves  the  testes  in  apparently  normal  condition,  but  the 
animals  are  not  able  to  fertilize  the  female.  Removal  of  the  testes, 
on  the  other  hand,  prevents  the  development  of  the  prostate  in  the 
young  animal  and  causes  atrophy  of  the  gland  in  the  adult.  Evi- 
dently, therefore,  the  testis  controls,  in  some  way,  probably  by  a 
hormone,  the  metabolic  processes  in  the  prostate.  Walker  believes 
that  the  prostatic  secretion  aids  in  rendering  the  spermatozoon 
properly  motile.  The  secretion  of  the  seminal  vesicles  in  the  rat 
exhibits  a  curious  property  of  clotting  upon  mixture  with  the 
secretion  of  a  small  gland  at  its  base — the  coagulating  gland.  If 
the  secretion  of  the  vesicles  follows  the  ejaculation  of  the  semen,  it 
is  possible  that  the  coagulation  of  the  former  serves  to  occlude  the 

*  See  Steinach,  "Archiv  f.  die  gesammte  Physiologic, "  56, 1894,  and  Walker, 
"Archiv  f.  Anatomic  u.  Physiologic,"  1889,  p.  313. 

f  Walker,  "Johns  Hopkins  Hospital  Reports,"  16,  1911,  and  "Johns  Hop- 
kins Bulletin,"  21,  1910. 


1006  THE    PHYSIOLOGY    OF    REPRODUCTION. 

vagina  in  the  female  and  thus  prevent  the  loss  of  the  fertilizing 
liquid.  The  union  of  spermatozoon  and  ovum  is  believed  to 
take  place  usually  in  the  Fallopian  tube,  and  under  normal  con- 
ditions only  one  spermatozoon  penetrates  into  the  egg.  The 
remainder  of  the  great  number  that  may  be  present  eventually 
perish.  The  changes  that  take  place  during  the  process  of  fer- 
tilization have  already  been  described  (p.  993). 

Chemistry  of  the  Spermatozoa. — Much  chemical  work  has 
been  done  upon  the  composition  of  spermatozoa,  particularly  in 
the  fishes.  The  results  have  been  most  interesting  from  a  chem- 
ical standpoint,  and  biologically  they  are  suggestive  in  that  the 
analytical  work  has  been  done  upon  the  heads  of  the  spermatozoa. 
These  heads  consist  entirely  of  nuclear  material,  and  contain  the 
substance  or  substances  which  convey  the  hereditary  characteristics 
of  the  father,  or,  to  speak  more  accurately,  of  the  race  to  which  the 
father  belongs.  Whatever  progress  may  be  made  in  the  understand- 
ing of  the  chemistry  of  this  material  is  a  step  toward  the  solution  of 
the  most  difficult  and  mysterious  side  of  reproduction,  the  power 
of  hereditary  transmission.  Miescher,  in  investigations  upon  the 
spermatozoa  of  salmon,  discovered  that  the  heads  are  composed 
essentially  of  an  organic  combination  of  phosphoric  acid,  since 
designated  as  nucleic  acid,  united  with  a  basic  albuminous  body, 
protamin.  This  view  has  been  confirmed  and  extended  by  later 
observers,  especially  by  Kossel  and  his  pupils.  *  The  head  of  the 
spermatozoon,  the  male  pronucleus  in  fertilization,  may  be  de- 
fined, in  the  case  of  the  fishes  at  least,  as  "a  salt  of  an  organic 
base  and  an  organic  acid,  a  protamin-nucleic  acid  compound." 
The  term  protamin  is  used  now  to  designate  a  group  of  closely 
related  proteins  obtained  from  the  spermatozoa  of  different 
animals.  The  special  protamin  of  each  species  is  designated  ac- 
cording to  the  zoological  name  of  that  species;  thus  the  protamin 
of  salmon  is  salmin,  of  herring  (Clupea  harengus),  clupein,  and  so 
on.  The  protamins  are  all  strong  bases;  their  aqueous  solutions 
give  an  alkaline  reaction,  and  they  unite  readily  with  various 
acids  to  form  well-defined  salts.  They  are  protein  bodies,  giv- 
ing the  biuret  reaction  readily  even  without  the  addition  of 
alkali,  and  they  are  precipitated  by  most  of  the  general  precipitants 
of  proteins,  such  as  the  neutral  salts,  the  alkaloidal  reagents,  etc. 
Their  solutions,  however,  are  not  coagulated  by  heat.  The  molec- 
ular formula  for  salmin  is  given  as  C30H57N17O6.  When  decom- 
posed by  the  action  of  acids  they  yield  simpler  basic  products, 
the  so-called  hexon  bases  or  diamino-bodies,  and  particularly  the 
base  arginin  (C6H14N4O2),  which  is  contained  in  the  protamin  of 

*  For  literature  and  details  of  the  chemistry  of  spermatozoa,  see  Burian, 
in  "Ergebnisse  der  Physiologic,"  vol.  Hi.,  part  i,  1904,  and  1906,  v.,  832. 


THE  MALE  REPRODUCTIVE  ORGANS.  1007 

the  spermatozoa  in  greater  abundance  than  in  any  other  protein. 
The  protamins  differ  from  most  other  protein  compounds  by  their 
relative  simplicity;  they  contain  no  cystin  grouping,  therefore  no 
sulphur;  no  carbohydrate  grouping  in  most  of  the  compounds 
examined;  and  no  tyrosin  complex.  In  the  spermatozoa  of  some 
fishes  the  protamins  are  replaced  by  more  complex  compounds 
belonging  to  the  group  of  histons  which  show  properties  somewhat 
intermediate  between  those  of  protamins  and  ordinary  proteins, 
and  in  general  it  may  be  said  that  the  head  of  the  spermatozoon, 
like  the  nuclei  of  cells  in  general,  consists  chiefly  of  a  nucleoprotein 
compound,  that  is,  a  compound  of  nucleic  acid  with  a  protein  body 
of  a  more  or  less  distinctly  basic  character.*  The  nucleic  acid  com- 
ponent of  the  spermatozoon  resembles  the  same  substance  as 
obtained  from  the  nuclei  of  other  cells.  In  the  spermatozoa  of  the 
salmon  this  nucleic  acid  has  the  formula  C40H56NUP4O26.  On 
decomposition  by  hydrolysis  it  yields  at  first  some  of  the  purin  bases 
(adenin,  guanin),  and  on  deeper  cleavage  a  number  of  compounds, 
including  the  pyrimidin  derivatives,  thymin,  uracil,  and  cytosin. 
While  the  chemical  studies  upon  spermatozoa,  thus  briefly  referred 
to,  have  greatly  extended  our  knowledge,  it  is  still  impossible  to 
say  that  they  have  given  any  information  concerning  the  peculiar 
functions  of  the  spermatozoa  in  fertilization. 

The  Act  of  Erection. — In  the  sexual  life  of  the  male  the  act  of 
erection  of  the  penis  during  coitus  offers  a  most  striking  physical 
phenomenon.  During  this  act  the  penis  becomes  hard  and  erect, 
owing  to  an  engorgement  with  blood.  The  structure  of  the  corpora 
cavernosa  and  corpus  spongiosum  is  adapted  to  this  function,  being 
composed  of  relatively  large  spaces  inclosed  in  trabeculse  of  connec- 
tive and  plain  muscle  tissue, — the  so-called  erectile  tissue.  Many 
theories  have  been  proposed  to  explain  the  mechanism  of  erection, 
but  it  is  generally  agreed  that  the  work  of  Eckhard  f  demonstrated 
the  essential  facts  in  the  process.  This  investigator  discovered  that 
in  the  dog  stimulation  of  the  nervi  erigentes  causes  erection.  These 
nerves  are  composed  of  autonomic  fibers  arising  from  the  sacral  por- 
tion of  the  spinal  cord  (see  Figs.  Ill  and  112).  They  arise  from  the 
sacral  spinal  nerves,  first  to  third  (dog),  on  each  side  and  help  to 
form  the  pelvic  plexus.  They  contain  vasodilator  fibers  to  the  penis, 
as  well  as  to  the  rectum  and  anus,  and  also  visceromotor  fibers  to  the 
descending  colon,  rectum,  and  anus.  Eckhard,  Loven,  and  others  J 
have  shown  that  when  these  fibers  are  stimulated  there  is  a  large 
dilatation  of  the  arterioles  in  the  erectile  tissue  of  the  penis  and  a 

*  Burian,  loc.  tit. 

t  Eckhard,  "Beitrage  zur  Anatomie  und  Physiologic,"  2,  123,  1863,  and 
4,  69,  1869. 

t  See  especially  Francois-Franck,  "Archives  de  Physiol.  norm,  et  pathol.," 
1895,  122,  138. 


1008  THE    PHYSIOLOGY    OF   REPRODUCTION. 

greatly  augmented  blood-flow  to  the  organ.  If  the  erectile  tissue 
is  cut  or  the  dorsal  vein  is  opened  the  blood-flow  under  usual  con- 
ditions is  a  slow  stream,  but  when  the  nervus  erigens  is  stimulated 
the  outflow  is  very  greatly  increased;  according  to  Eckhard's 
measurements,  eight  to  fifteen  times  more  blood  flows  out  of  the 
organ.  The  act  of  erection  is  therefore  due  essentially  to  a  vas- 
cular dilatation  of  the  small  arteries  whereby  the  cavernous  spaces 
become  filled  with  blood  under  considerable  pressure.  The  caver- 
nous tissues  are  distended  to  the  limits  permitted  by  their  tough, 
fibrous  wall.  It  seems  probable  that  the  turgidity  or  rigidity  of 
the  congested  organ  is  completed  by  a  partial  occlusion  of  the 
venous  outflow,  which  is  effected  by  a  compression  of  the  efferent 
vein  by  means  of  the  extrinsic  muscles  (ischio  and  bulbocavernosus) 
and  possibly  by  the  intrinsic  musculature  as  well.  This  compres- 
sion does  not  occlude  the  blood-flow  completely,  but  serves  to  in- 
crease greatly  the  venous  pressure.  This  explanation  of  the  act  of 
erection,  while  no  doubt  correct,  so  far  as  it  goes,  leaves  undeter- 
mined the  means  by  which  the  dilatation  of  the  small  arteries  is 
produced.  Vasodilator  nerve  fibers  in  general  are  assumed  to  pro- 
duce a  dilatation  by  inhibiting  the  peripheral  tonicity  of  the 
arterial  walls.  If  this  explanation  is  applied  to  the  case  under 
consideration  it  forces  us  to  believe  that  throughout  life,  except 
for  the  very  occasional  acts  of  erection,  the  arteries  in  the  penis 
are  kept  in  a  constant  condition  of  active  tone.  Moreover,  on  this 
view  we  should  expect  that  section  of  the  vasoconstrictor  fibers  to 
the  penis,  by  abolishing  the  tone  of  the  arteries,  would  also  cause 
erection.  These  constrictor  fibers  arise  from  the  second  to  fifth 
lumbar  spinal  nerves,  and  reach  the  organ  by  way  of  the  hypo- 
gastric  nerve  and  plexus  and  the  pudic  nerve.  No  such  result  of 
their  section  is  reported  and  it  seems  that  in  the  matter  of  erec- 
tion the  actual  mechanism  of  the  great  dilatation  caused  by  the 
nervi  erigentes  still  contains  some  points  that  need  investigation. 

The  Reflex  Apparatus  of  Erection  and  Ejaculation.— The 
dilatation  of  the  arteries  of  the  penis  during  erection  is  normally  a 
reflex  act,  effected  through  a  center  in  the  lumbar  cord.  This  center 
may  be  acted  upon  by  impulses  descending  from  the  brain,  as 
in  the  case  of  erotic  sensations,  or  by  afferent  impulses  arising  in 
some  part  of  the  genital  tract, — from  the  testes  themselves,  from 
the  urethra  or  prostate  gland,  and  especially  from  the  glans  penis. 
Mechanical  stimulation  of  the  glans  leads  to  erection,  and  Eckhard 
showed  in  dogs  that  section  of  the  pudic  nerve  prevents  this  reflex 
from  occurring,  proving,  therefore,  that  the  sensory  fibers  concerned 
run  in  the  pudic  nerve.  Stimulation  of  these  latter  fibers  leads  also 
to  erotic  sensations  and  eventually  to  the  completion  of  the  sexual 
orgasm.  This  latter  act  brings  about  the  forcible  ejection  of  the 


THE  MALE  REPRODUCTIVE  ORGANS.  1009 

sperm  through  the  urethra.  It  is  initiated  by  contractions  of  the 
musculature  of  the  vasa  deferentia,  ejaculatory  duct,  the  seminal 
vesicles,  and  the  prostate  gland,  which  force  the  spermatozoa,  to- 
gether with  the  secretions  of  the  vesicles  and  prostate  gland,  into 
the  urethra,  whence  they  are  expelled  in  the  culminating  stage  of 
the  orgasm  by  the  rhythmical  contractions  of  the  ischiocavernosus 
and  bulbocavernosus  muscles,  together  with  the  constrictor  urethrse. 
The  immediate  center  for  this  complex  reflex  is  assumed  to  lie  in 
the  lumbar  cord,  since,  according  to  the  experiments  of  Goltz, 
mechanical  stimulation  of  the  glans  in  dogs  causes  erection  and 
seminal  emission  after  the  lumbar  cord  is  severed  from  the  rest  of 
the  central  nervous  system.  Under  ordinary  conditions  the  act  is 
accompanied  by  strong  psychical  reactions  which  indicate  that 
the  cortical  region  of  the  cerebrum  is  involved.  It  is  interesting  in 
this  connection  to  find  that  electrical  stimulation  of  a  definite  re- 
gion in  the  cortex*  of  dogs  may  cause  erection  and  ejaculation. 

*  Pussep,   quoted   from   Hermann's   "  Jahresbericht    der    Physiologie," 
vol.  xi,  1903. 

64 


CHAPTER   LIV. 

HEREDITY— DETERMINATION  OF  SEX-GROWTH  AND 

SENESCENCE. 

Heredity. — The  development  of  the  fertilized  ovum  offers  two 
general  phenomena  for  consideration:  First,  the  mere  fact  of  mul- 
tiplication by  which  an  infinite  number  of  cells  are  produced  by 
successive  cell-divisions;  second,  the  fact  that  these  cells  become 
differentiated  in  structure  in  an  orderly  and  determinate  way  so  as 
to  form  an  organism  of  definite  structure  like  those  which  gave 
origin  to  the  ovum  and  the  spermatozoon.  In  other  words,  the 
fertilized  ovum  possesses  a  property  which,  for  want  of  a  better 
term,  we  may  designate  as  a  form-building  power.  The  ovum 
develops  true  to  its  species,  or,  indeed,  more  or  less  strictly  in  accord- 
ance with  the  peculiarities  of  structure  characteristic  of  its  parents. 
The  object  of  a  complete  theory  of  heredity  is  to  ascertain  the  me- 
chanical causes — that  is,  the  physicochemical  properties — resi- 
dent in  the  fertilized  ovum  which  impel  it  to  follow  in  each  case  a 
definite  line  of  development.  The  discussions  upon  this  point  have 
centered  around  two  fundamentally  different  conceptions  designated 
as  evolution  and  epigenesis. 

Evolution  and  Epigenesis. — The  earlier  embryologists  found  a 
superficial  explanation  of  this  problem  in  the  view  that  in  the  germ 
cells  there  exists  a  miniature  animal  already  preformed,  and  that 
its  development  under  the  influence  of  fertilization  consists  in  a 
process  of  growth  by  means  of  which  the  minute  organism  is 
unfolded,  as  it  were.  The  process  of  development  is  a  process  of 
evolution  of  a  pre-existing  structure.  Inasmuch  as  countless  in- 
dividuals develop  in  successive  generations,  it  was  assumed  also 
that  in  the  germ  cell  there  are  included  countless  miniature  organ- 
isms,— one  incased,  as  it  were,  in  the  other.  Some  of  the  embry- 
ologists of  that  period  conceived  that  the  undeveloped  embryos  are 
contained  in  the  ovum, — the  ovists, — while  others  believed  that 
they  are  present  in  the  spermatozoon,  the  animalculists.  Other 
embryologists  pointed  out  that  the  fertilized  egg  shows  no  indication 
of  a  preformed  structure,  and  therefore  concluded  that  development 
starts  from  an  essentially  structureless  cell,  and  consists  in  the 
successive  formation  and  addition  of  new  parts  which  do  not  pre 

1010 


HEREDITY.  1011 

exist  as  such  in  the  fertilized  egg.  This  view  in  contradistinction 
to  the  evolution  theory  was  designated  as  epigenesis.  Microscopi- 
cal investigation  has  demonstrated  beyond  all  doubt  that  the  fer- 
tilized ovum  is  a  simple  cell  devoid  of  any  parts  or  organs  resem- 
bling those  of  the  adult,  and  the  evolution  theory  in  its  crude  form 
has  been  entirely  disproved.  Nevertheless  the  controversy  be- 
tween the  evolutionists  and  epigenesists  still  exists  in  modified 
form.  For  it  is  evident  that  in  the  fertilized  ovum  there  may  exist 
preformed  mechanisms  or  complexes  of  molecules  which,  while  in  no 
way  resembling  anatomically  the  subsequently  developed  parts  of 
the  organism,  nevertheless  are  the  foundation  stones,  to  use  a  figure 
of  speech,  upon  which  the  character  of  the  adult  structure  depends. 
Such  a  view  in  one  form  or  another  is  probably  held  by  most  bi- 
ologists, since  it  avoids  the  well-nigh  inconceivable  difficulties  of- 
fered by  a  completely  epigenetic  theory.  If  the  fertilized  ovum 
of  one  animal  is  in  the  beginning  substantially  similar  to  that  of 
any  other  animal  the  epigenesist  must  ascertain  what  combination 
of  conditions  during  the  process  of  development  causes  the  egg, 
in  a  dog,  for  instance,  to  develop  always  into  a  dog,  and  moreover 
into  a  certain  species  of  dog  resembling  more  or  less  exactly  the 
parent  organisms.  The  infinite  difficulties  encountered  by  such  a 
point  of  view  are  apparent  at  once.  In  this,  as  in  other  similar  prob- 
lems, experimental  work  is  gradually  accumulating  facts  which 
throw  some  light  upon  the  matter  and  may  eventually  lead  us  to  the 
right  explanation.  It  has  been  made  highly  probable  that  the  chro- 
matin  material  in  the  nuclei  of  the  germ  cells,  the  chromosomes, 
constitute  the  physical  basis  of  hereditary  transmission  of  racial 
characteristics.  In  the  fertilized  egg,  it  will  be  remembered,  half 
of  the  chromosomes  come  from  the  mother  and  half  from  the 
father,  and  there  is  good  reason  for  believing  that  the  maternal 
chromosomes  are  the  bearers  of  the  maternal  characteristics,  and 
the  chromosomes  derived  from  the  spermatozoon  convey  the 
hereditary  traits  of  the  father.  It  must  not  be  understood  from 
this  statement  that  the  characteristics  of  the  parent  are  directly 
transmitted  or  handed  over  to  the  reproductive  cells.  On  the 
contrary,  the  ova  of  the  mother  are  cells  lineally  descended  from 
the  ovum  that  gave  rise  to  her  as  an  individual,  and  the  struc- 
tures or  determiners  in  the  chromosomes  of  the  ova  are  not  derived 
from  the  body  of  the  mother,  but  are  transmitted  from  the  original 
ovum.  By  this  means  there  is  constituted  a  physical  continuity 
of  the  germinal  material  from  generation  to  generation.  The 
hereditary  characteristics  contained  in  the  structure  of  the  germ 
cells  are  racial — they  belong  to  the  stock  and  are  not  created  anew 
in  each  generation.  The  spermatozoon,  so  far  as  it  enters  into  the 
structure  of  the  fertilized  ovum,  consists  only  of  chromatin  material 


1012  THE    PHYSIOLOGY    OF    REPRODUCTION. 

or  chromosomes  conveying  the  carriers  or  determiners  of  heredi- 
tary traits  belonging  to  the  parental  stock  of  germ  plasm.  The 
ovum  contains  chromosomes  that  in  the  same  way  add  hereditary 
characteristics  from  the  maternal  strain  of  germ  plasm.  When 
these  two  cells  unite  a  new  individual  is  begun,  and  his  hereditary 
traits  are,  so  to  speak,  defined,  and  they  constitute  a  mixture  from 
two  strains,  but  a  mixture  the  composition  of  which  may  be  in- 
finitely varied.  Modern  biologists  insist  that  the  cytoplasm  of  the 
ovum  also  conveys  certain  general  hereditary  characteristics  of 
a  fundmental  kind,  such  as  the  polarity  and  symmetry  of  the  future 
organism  and  possibly  also  its  pattern  or  the  relative  position  of 
future  organs.  Such  a  view,  it  will  be  noticed,  implies  at  once 
preformed  structures  in  the  gametes  and  constitutes  one  form  of 
an  evolutionary  hypothesis.  This  view  is  further  supported  by 
the  interesting  experiments  of  Wilson.* 

This  author  has  shown  that  in  certain  mollusks  (Dentalium  or 
Patella),  if  a  portion  of  the  egg  is  cut  off,  the  remaining  portion  upon 
fertilization  develops  into  a  defective  animal  that  is  not  a  whole 
embryo,  but  rather  a  piece  or  fragment  of  an  embryo.  Or  if  the 
fertilized  egg  after  its  first  segmentation  is  separated  artificially 
into  two  independent  cells,  each  develops  an  embryo,  but  neither 
one  is  completely  formed — each  is  lacking  in  certain  structures  and 
the  two  must  be  taken  together  to  constitute  an  entirely  normal  ani- 
mal. By  experiments  of  this  kind  it  has  been  shown  that  certain  def- 
inite portions  of  the  egg  are  responsible  for  the  formation  of  partic- 
ular organs  ill  the  adult.  If  these  portions  of  the  egg  are  removed 
the  organs  in  question  are  not  developed.  Many  interesting  gen- 
eral theories  of  heredity  have  been  proposed  by  Darwin,  Nageli, 
Weissmann,  Mendel,  Galton,  Brooks,  and  others.  It  is  impossible 
to  give  here  an  outline  of  all  these  theories,  but  a  word  may  be 
said  regarding  the  work  of  de  Vries  and  Mendel,  which  have  given 
rise  recently  to  so  much  discussion.  For  fuller  information  the 
reader  is  referred  to  special  treatises  on  the  subject.f  According 
to  the  well-known  views  of  Darwin  in  regard  to  the  action  of 
natural  selection  it  was  assumed  that  new  varieties  and  species 
are  formed  by  the  cumulative  action  of  selection  upon  small 
fluctuating  variations.  By  this  cumulative  selection  certain 
variations  are  preserved  and  strengthened  until  they  are  suffi- 
ciently marked  to  constitute  a  specific  difference,  the  process 
requiring  naturally  a  long  period  of  time.  In  contrast  with  this 
view  de  Vries  has  suggested  what  is  commonly  known  as  the 
theory  of  mutations.  According  to  this  view  the  variability  in 

*  Wilson,  "Science,"  February  24,  1905,  for  a  popular  discussion;  also 
"Journal  of  Experimental  Zoology,"  1,  1  and  197,  1904,  and  2,  371,  1905. 

fHertwig,  "The  Biological  Problems  of  To-day";  Delage,  "L'heredite" 
et  les  grands  problemes  de  la  biologic  generate,"  1903;  Thomson,  "Heredity," 
1908;  Conklin,  "Heredity  and  Environment,"  1914. 


HEREDITY.  1013 

the  germ  plasm  is  such  that  it  may  at  times  give  rise  not  to  fluctu- 
ating variations,  but  to  marked  and  permanent  variations,  and 
these  latter,  if  advantageous  to  the  animal,  are  preserved  by 
natural  selection.  Such  permanent  variations  are  known  as 
mutations  or  "sports,"  and  in  consequence  of  their  formation 
and  preservation  the  process  of  evolution  may  proceed  much 
more  rapidly  than  was  assumed  to  be  the  case  in  the  original 
form  of  Darwin's  hypothesis.  The  contribution  made  to  our 
understanding  of  heredity  by  the  work  of  Mendel  and  those  who 
have  used  his  conceptions  is  most  significant.  By  the  Mendelian 
law  or  Mendelian  inheritance  is  meant  in  the  first  place  the  general 
idea  that  characteristics  handed  down  by  inheritance  from  parents 
to  offspring  may  be  treated  as  separate  units.  It  is  implied  in  this 
view  that  these  unit  characters  are  conveyed  by  definite  substances 
or  structures  in  the  germ  plasm  which,  for  convenience,  have  been 
designated  as  "determiners"  or  "unit-f actors."  Their  nature 
is,  of  course,  unknown.  In  some  cases  parental  characteris- 
tics may  apparently  blend  in  the  children,  as,  for  example,  in  the 
case  of  color,  the  mulatto  being  in  this  regard  a  blend  of  a  white 
and  a  black  parent.  In  most  cases,  however,  there  is  no  blend- 
ing, but  an  alternation  of  one  or  the  other  of  a  pair  of  contrasting 
characteristics.  As  regards  such  a  pair  of  alternating  character- 
istics Mendel  found  that  one  will  be  dominant,  the  other  recessive, 
whenever  they  are  brought  together.  That  is  to  say,  if  each  parent 
possesses  one  of  such  alternating  characteristics,  brown  eyes  and 
blue  eyes,  for  example,  the  children  will  all  show  the  dominant 
characteristic,  in  this  case  brown  eyes,  but  the  other  characteristic 
will  be  present  in  a  recessive  or  concealed  form.  In  the  hybrids 
possessing  both  characteristics  the  germ  cells  are  so  divided  that 
half  of  them  possess  the  dominant  alone  and  half  the  recessive 
alone.  This  constitutes  the  law  of  the  "purity  of  the  germ  cells" 
or  of  the  "segregation  of  the  gametes."  If  two  such  hybrids  breed 
together  it  follows  from  the  law  of  probabilities  that  in  the  offspring 
three  out  of  four  will  show  the  dominant  characteristic  and  one  the 
recessive  characteristic.  Moreover,  of  those  that  show  the  domi- 
nant characteristic  two  will  be  hybrids,  containing  also  the  recess- 
ive, but  one  will  be  a  pure  dominant.  This  result  may  be  under- 
stood from  the  following  formula,  in  which  D  and  R  represent 
respectively  the  dominant  and  the  recessive: 

D— R 

|       |  =  1  DD,  2D(R)  and  1  RR. 
D— R 

If  two  pure  recessives  or  two  pure  dominants  breed  together,  only 
a  recessive  or  a  dominant,  as  the  case  may  be,  will  be  exhibited 
in  the  offspring,  and  in  this  way  pure  characteristics  may  be 


1014  THE    PHYSIOLOGY    OF    REPRODUCTION. 

selected  and  established.  Such  a  process  of  selection  is  simple  in 
the  case  of  the  recessive  characteristics,  but  in  the  case  of  the 
dominant  it  is,  of  course,  more  difficult  to  distinguish  between  the 
DD  and  the  D(R).  The  distinction  may  be  made  by  breeding 
with  an  animal  showing  the  recessive.  If  the  dominant  is  pure, 
all  of  the  offspring  will  exhibit  the  dominant  characteristics.  If, 
on  the  contrary,  it  is  a  hybrid,  the  offspring  will  be  half  dominant 
and  half  recessive,  according  to  the  formula: 

D— R 

|       |  =  DR,  DR,  RR,  RR. 
R— R 

The  many  attempts  to  verify  this  law  in  breeding  have  shown  that 
it  expresses  probably  a  great  truth,  although  the  application  of  it 
to  the  practical  purposes  of  breeding  is  beset  with  many  compli- 
cations. The  newer  experimental  work  in  heredity  has  emphasized 
the  importance  of  breeding  experiments  made  with  what  are  known 
as  "  pure  lines,"  that  is  to  say,  with  those  plants  or  animals  which 
are  capable  of  propagation  without  cross  fertilization.*  These 
experiments  have  tended  to  prove  that  the  characteristics  of 
each  race  or  species  are  inherent  in  its  germ  plasm  and  will  breed 
true  if  not  fertilized  or  mixed  with  germ  plasm  from  another 
individual  of  different  origin.  When  there  is  cross  fertilization,  the 
offspring  are  hybrids  which  exhibit  some  of  the  characteristics  of 
each  parent.  According  to  the  Mendelian  law,  the  unit  factors 
conveying  these  characteristics  are  sorted  out  or  segregated  in  the 
reproductive  cells  of  the  parents.  If  a  cross  fertilization  is  effected, 
for  example,  between  a  white  and  a  crimson  flower  of  the  same  spe- 
cies the  offspring  show  an  intermediate  pink  color.  The  fusion  of 
characteristics  is,  however,  only  apparent,  for  in  the  reproductive 
cells  of  the  pink  hybrids  the  factors  conveying  the  white  and  crim- 
son characters  will  again  be  separated.  That  is  to  say,  one-half 
of  the  reproductive  cells  will  have  the  factor  for  white  and  one-half 
the  factor  for  crimson.  Two  pink  hybrids  bred  together  will 
produce  offspring  whose  color  characteristics  may  be  predicted, 
according  to  the  Mendelian  principle,  as  follows: 

Pink  Hybrid  Pink  Hybrid 

WC  WC 


Pollen    W  C  W  C    Ovules 

1-2  34 

Combination  1  and  3  will  give  a  pure  white. 
Combination  1  and  4  will  give  a  hybrid  pink. 
Combination  2  and  3  will  give  a  hybrid  pink. 
Combination  2  and  4  will  give  a  pure  crimson. 

*  For  a,  general  presentation  see  "American  Naturalist,"  February  and 
March,  1911,  Jennings  and  others. 


DETERMINATION    OF    SEX.  1015 

The  results  obtained  from  crossing  hybrids  is  not  always  as  simple 
as  is  indicated  in  this  schema,  since  so-called  characteristics  may 
be  dependent  not  upon  a  single  but  upon  several  factors.  In 
general,  however,  the  Mendelian  principles  of  the  existence  of  unit 
characters  and  segregation  of  these  characters  in  the  germ  cells  are 
accepted.  They  throw  some  light  upon  what  was  before  a  very 
mysterious  process.  The  point  of  view  suggested  by  these  principles 
leads  us  to  lay  great  stress,  in  the  matter  of  breeding,  upon  the  im- 
portance of  the  characteristics  of  the  racial  strains,  and  to  value 
less  than  formerly  the  importance  of  characteristics  acquired  during 
the  life  of  the  individual  parent,  or,  expressed  in  another  way,  the 
modern  tendency  is  to  believe  that  "nature  counts  for  more  than 
nurture."  As  a  matter  of  fact  in  the  development  of  an  individual 
both  nature  and  nurture  play  important  parts;  nature,  that  is  the 
character  of  the  stock,  determines  the  potential  possibilities  in  the 
fertilized  ovum,  while  nurture,  or  the  character  of  the  environment, 
is  influential  in  exciting  or  repressing  the  development  of  these 
possibilities.  The  full  comprehension  of  the  fundamental  import- 
ance of  the  heredity  factor  is  mainly  responsible  for  the  modern 
movement  of  eugenics,  which  hopes  to  improve  the  quality  of  the 
race  by  limiting  the  growth  of  poor  stock  in  mankind  and  encour- 
aging the  breeding  from  the  best  stock. 

Determination  of  Sex. — The  conditions  which  lead  to  the 
determination  of  the  sex  of  the  developing  ovum  have  attracted 
much  investigation  and  speculation.  In  the  -absence  of  precise 
data  very  numerous  and  oftentimes  very  peculiar  theories  have 
been  advanced.*  Such  views  as  the  following  have  been  main- 
tained: that  the  sex  is  determined  by  the  ova  alone;  that  it  is 
determined  by  the  spermatozoa  alone;  that  one  side  (right  ovary 
or  testis)  contains  male  elements,  the  other  female;  that  the  sex 
is  a  result  of  the  interaction  of  the  ovum  and  spermatozoon,  the 
most  virile  element  producing  its  own  sex,  or  according  to  another 
possibility  "the  superior  parent  produces  the  opposite  sex";  that 
the  sex  depends  on  the  time  relation  of  coitus  to  menstruation, 
fertilization  before  menstruation  favoring  male  births,  after  men- 
struation female  births;  that  it  depends  upon  the  nutritive  con- 
ditions of  the  ovum  during  development  or  of  the  maternal  parent ; 
that  it  depends  upon  the  relative  ages  of  the  parents;  that  there 
are  preformed  male  and  female  ova  and  male  and  female  sper- 
matozoa, etc.  What  we  may  call  the  scientific  study  of  the  problem 
began  with  the  collection  of  statistics  of  births.  Statistics  in  Europe 
of  5,935,000  births  indicate  that  106  male  children  are  born  to 

*  For  accounts  of  the  various  theories  and  discussion,  see  Morgan,  "He- 
redity and  Sex,"  1913;  Wilson,  "Proceedings  of  the  Roy.  Soc.,"  B,.88,  1914 
(Croonian  Lecture);  Lenhossek,  "Das  Problem  der  geschlechtsbestimmenden 
Ursachen,"  1903. 


1016  THE    PHYSIOLOGY    OF    REPRODUCTION. 

100  female,  and  the  data  from  other  countries  show  the  same 
fact  of  an  excess  of  male  children.  Owing  to  the  greater  death-rate 
of  the  male,  the  proportion  of  male  to  female  in  the  adult  population 
of  Europe  is  as  1000  to  1024.  Examination  of  these  statistics  with 
reference  to  determining  conditions  led  to  the  formulation  of  the  so- 
called  Hof acker-Sadler  law  or  laws,  which  may  be  stated  as  follows: 
(1)  When  the  man  is  older  than  the  woman  the  ratio  of  male 
births  is  increased  (113  to  100).  (2)  When  the  parents  are 
of  equal  age  the  ratio  of  female  births  is  increased  (93.5  males  to 
100  females).  (3)  When  the  woman  is  older  the  ratio  of  female 
births  is  still  further  increased  (88.2  to  100).  These  laws  have 
been  corroborated  by  some  statisticians  and  contradicted  or  modi- 
fied by  others.  Ploss  attempted  to  show  that  poor  nutritive  con- 
ditions affecting  the  parents,  especially  the  mother,  favor  the 
birth  of  boys.  Dusing  combined  these  results  in  a  sort  of  general 
compensatory  law  of  nature,  according  to  which  a  deficiency  in 
either  sex  leads,  by  a  process  of  natural  selection,  to  an  increase 
in  the  births  of  the  opposite  sex.  Thus,  when  males  are  few  in 
number, — as  the  result,  for  instance,  of  wars, — females  marry 
later  and  more  males  are  produced.  When  males  are  in  excess  early 
marriages  are  the  rule  and  this  condition  favors  an  excess  of  female 
births.  However  interesting  these  statistics  may  be,  it  is  very 
evident  that  they  do  not  touch  the  real  problem  of  the  cause  of  the 
determination  of  sex. 

Modern  work  has  turned  largely  to  observations  and  direct 
experiments  upon  the  lower  animals,  and  particularly  to  cytolog- 
ical  studies  of  the  reproductive  cells.  The  trend  of  this  work  tends 
to  oppose  an  older  view  founded  largely  upon  experiments  on  frogs, 
bees,  and  wasps,  according  to  which  the  sex  is  controlled  or  may  be 
controlled  by  the  conditions  of  nourishment  during  development, 
favorable  conditions  of  nutriment  leading  to  the  development  of 
female  cells  from  the  germinal  epithelium  of  the  embryo.  On 
the  contrary,  it  is  now  believed  that  while  such  external  conditions 
may  affect  the  sex  ratio,  the  factors  that  actually  determine  sex  are 
internal  and  the  sex  of  the  fertilized  ovum  is  fixed  at  the  time  of 
fertilization.  The  view  that  holds  at  present  connects  the  deter- 
mination of  sex  with  the  presence  or  absence  of  an  accessory 
chromosome,  the  z-chromosome,  in  the  matured  spermatozoon. 
In  many  animals  the  spermatocyte,  like  the  other  cells  of  the  male, 
contains  an  odd  number  of  chromosomes.  In  man,  for  example, 
the  number  is  given  as  47.  When  synapsis  of  these  chromosomes 
occurs  in  the  process  of  maturation,  23  pairs  are  formed  and  one 
odd  one,  the  z-chromosome.  At  the  reduction  division  to  form  the 
spermatozoa  these  pairs  separate,  one  going  to  each  daughter-cell, 
but  the  a>chromosome  being  unpaired  goes  to  one  only  of  the 


GROWTH    AND    SENESCENCE. 


1017 


daughter-cells.  As  a  consequence  two  kinds  of  spermatozoa  are 
formed  in  equal  numbers,  one  kind  possessing  the  z-chromosome, 
and  the  other  without  this  element.  In  the  ova,  on  the  contrary, 
there  is  an  even  number  of  chromosomes,  the  ^-chromosomes  are 
paired  like  the  others  and  the  matured  ova  all  have,  therefore,  an 
z-chromosome.  Much  evidence  has  been  brought  forward  to  show 
that  when  a  spermatozoon  containing  an  z-chromosome  fertilizes 
an  ovum  a  female  results,  while  an  ovum  fertilized  by  a  sperma- 
tozoon without  an  x-chromosome  yields  a  male.  This  result  is  ex- 
pressed in  the  following  diagram  in  which  the  presence  of  an 
x-chromosome  is  represented  by  an  x. 


Matured  spermatozoa. 


Matured  ova. 


Fig.  307. 


The  combinations  1,  3  and  1,  4  give  rise  to  females,  and  the 
combinations  2,  3  and  2,  4  give  rise  to  females.  It  is  said  that 
in  some  animals  (aphids)  only  the  spermatozoa  containing  an 
a>chromosome  mature,  and  as  a  result  all  the  progeny  from  sexual 
union  are  females.  In  some  cases  the  male  gamete  has  two 
^-chromosomes,  but  of  unequal  size,  the  larger  one  being  then 
designated  as  the  z-chromosome  and  the  smaller  one  as  the 
y-chromosomes.  In  the  union  with  the  ova  the  spermatozoa  with 
^/-chromosomes  produce  males;  the  others,  females. 

We  owe  the  establishment  of  this  important  generalization 
largely  to  American  investigators  (McClung,  Wilson,  Stevens). 
It  enables  us  to  treat  sex  as  a  Mendelian  characteristic  trans- 
mitted by  certain  hereditary  units  or  determiners.  When  two 
of  these  are  united  in  a  fertilized  ovum  a  female  results,  while  a 
single  one  gives  rise  to  a  male.  From  this  point  of  view  it  has 
been  possible  to  construct  satisfactory  schemata  to  explain  the 
many  known  instances  of  sex-linked  inheritance,  such  as  hemo- 
philia and  color-blindness  in  man. 

Growth  and  Senescence. — The  body  increases  rapidly  after 
birth  in  size  and  weight.  It  is  the  popular  idea  that  the  rate  of 
growth  increases  up  to  maturity  and  then  declines  as  old  age  ad- 
vances. As  a  matter  of  fact,  careful  examination  of  the  facts  shows 


1018  THE    PHYSIOLOGY    OF    REPRODUCTION. 

that  the  rate  of  growth  decreases  from  birth  to  old  age,  although  not 
uniformly.  At  the  pubertal  period  and  at  other  times  its  downward 
tendency  may  be  arrested  for  a  time.  But,  speaking  generally,  the 
maximum  rate  of  growth  is  reached  some  time  during  the  intra- 
uterine  period,  and  after  birth  the  curve  falls  steadily.  Senescence 
has  begun  to  appear  at  the  time  we  are  born.*  Thus,  according  to 
the  statistics  of  Quetelet,  the  average  male  child  weighs  at  birth  6J 
pounds.  At  the  end  of  the  first  year  it  weighs  18 %  pounds,  a  gain  of 
12  pounds.  At  the  end  of  the  second  year  it  weighs  23  pounds,  a 
gain  of  only  4-J  pounds,  and  so  on,  the  rate  of  increase  falling  rap- 
idly with  advancing  years.  Jackson  f  has  published  an  interesting 
series  of  observations  upon  the  relative  and  absolute  growth  of 
the  human  fetus  and  its  different  organs  during  the  intra-uterine 
period.  Relative  growth  is  defined  as  the  "  ratio  of  the  gain 
during  a  given  period  to  the  weight  at  the  beginning  of  the  period." 
From  this  standpoint  he  finds  that  the  maximum  rate  of  growth 
occurs  during  the  first  month  of  fetal  life.  As  determined  by 
the  volume  of  the  fetus  the  ovum  increases  more  than  10,000 
times  in  size  during  this  period.  In  the  succeeding  months  of 
intra-uterine  life  the  relative  monthly  growth  rate  may  be  expressed 
by  the  figures  74,  11,  1.75,  .82,  .67,  .50,  .47,  .45.  During  this  period 
the  absolute  weight  is,  of  course,  increasing  rapidly,  and  according 
to  Jackson's  observations  the  total  weight  of  the  embryo  may  be 

calculated  at  any  time  from  the  formula  weight  (g)  =(  -    '  \ 

\        6i        ) 

Friedenthal  t  gives  the  following  figures  for  the  growth  of  the 
fetus,  including  the  membranes  and  placenta: 

AGE  IN  -TTT  /-.  ABSOLUTE  INCREASE  PERCENTAGE  IN- 

DAYB.  CjM8>         PER  DAY  (QMS.).  CREASE  PER  DAY. 

0  0.000004 

8  0.03  0.0037                  90,000 

17  0.86  0.092  307 

20  1.4  0.18  16 

26  2.0  0.1  6 

35  2.9  0.1  4.5 

40  19.0  3.2  29 

60  220.0  10.0  8.4 

100  800.0  14.5  3.0 

120  1200.0  20.0  2.0 

196  2800.0  21.0  1.1 

250  3800.0  19.0  0.6 

280  4500.0  23.0  0.5 

The  statistics  of  extra-uterine  growth  have  been  collected  and 
tabulated  with  great  care  by  a  number  of  observers;  for  this 

*  See  Minot,  "Journal  of  Physiology,"  12,  97. 

t  Jackson,  "The  American  Journal  of  Anatomy,"  9,  119,  1909. 

I  Friedenthal,  "Physiologic  d.  Menschenwachstums,"  1914. 


GROWTH    AND    SENESCENCE.  1019 

country  especially  by  Bowditch,  Porter,  and  Beyer.*  An  inter- 
esting feature  of  the  records  collected  by  Bowditch  is  the  proof 
that  the  prepubertal  acceleration  of  growth  comes  earlier  in  girls 
.than  in  boys,  so  that  between  the  ages  of  twelve  and  fifteen 
the  average  girl  is  heavier  and  taller  than  the  boy.  Later,  the  boy's 
growth  is  accelerated  and  his  stature  and  weight  increase  beyond 
that  of  the  girl.  Robert  son  f  has  accumulated  some  facts  which 
indicate  that  the  growth  of  the  individual  does  not  proceed  with 
a  uniformly  accelerated  or  a  uniformly  retarded  velocity,  but 
rather  in  cycles,  each  of  which,  expressed  graphically,  takes  the 
form  of  an  S-shaped  curve.  He  believes  that  there  are  three, 
possibly  four,  of  these  curves.  The  first  begins  with  the  implanta- 
tion of  the  ovum  and  terminates  about  a  year  after  birth.  From 
observations  made  on  the  weights  of  infants  born  before  and  after 
the  normal  period  he  concludes  that  the  increments  of  weight  in 
each  case  follow  the  same  curve.  An  infant  born  after  the  normal 
period  has  increased  in  weight  while  in  the  uterus  as  it  would 
have  grown  in  the  same  period  of  extra-uterine  life.  The  second 
cycle  starts  toward  the  close  of  the  first  year,  reaches  its  maximum 
at  five  and  one-half  years,  and  then  falls  off.  The  third  cycle 
begins  at  the  end  of  the  second,  reaches  its  maximum  at  puberty, 
and  terminates  at  adult  life.  The  signs  of  old  age  may  be  de- 
tected in  other  ways  than  by  observations  upon  the  rate  of  growth. 
Changes  take  place  in  the  composition  of  the  tissues;  these  changes, 
at  first  scarcely  noticeable,  become  gradually  more  obvious  as  old 
age  advances:  The  bones  become  more  brittle  from  an  increase  in 
their  inorganic  salts,  the  cartilages  become  more  rigid  and  calca- 
reous, the  crystalline  lens  gradually  loses  its  elasticity,  the  muscles 
lose  their  vigor,  the  hairs  their  pigment,  the  nuclei  of  the  nerve 
cells  become  smaller,  and  so  on.  In  every  way  there  is  increasing 
evidence,  as  the  years  grow,  that  the  metabolism  of  the  living  mat- 
ter of  the  body  becomes  less  and  less  perfect;  the  power  of  the 
protoplasm  itself  becomes  more  and  more  limited,  and  we  may 
suppose  would  eventually  fail,  bringing  about  what  might  be  called 
a  natural  death.  As  a  matter  of  fact,  death  of  the  organism  usually 
results  from  the  failure  of  some  one  of  its  many  complex  mechanisms, 
while  the  majority  of  the  tissues  are  still  able  to  maintain  their  exis- 
tence if  supplied  with  proper  conditions  of  nourishment.  The  phys- 
iological evidences  of  an  increasing  senescence  warrant  the  view, 
however,  that  death  is  a  necessary  result  of  the  properties  of  living 
matter  in  all  the  tissues  except  possibly  the  reproductive  elements. 

*  See  Bowditch,  "Report  of  State  Board  of  Health  of  Massachusetts," 
1877,  1879,  and  1891;  Porter,  "Transactions,  Academy  of  Science,"  St.  Louis, 
1893-94;  Beyer,  "Proceedings  of  United  States  Naval  Institute,"  21,  297, 
1895. 

f  Robertson,  "American  Journal  of  Physiology,"  37,  1,  1915. 


1020  THE    PHYSIOLOGY    OF    REPRODUCTION. 

The  course  of  metabolism  is  such  that  it  is  self-limited,  and  even 
if  perfect  conditions  were  supplied  natural  death  would  eventually 
result.  As  a  rule,  however,  death  is,  so  to  speak,  accidental 
rather  than  natural.  This  point  of  view  was  emphasized  by  Ray . 
Lankester  in  the  distinction  which  he  drew  between  specific 
longevity  and  potential  longevity.  By  specific  longevity  he  des- 
ignated the  expectation  of  life  at  birth  of  a  normal  individual, 
this  expectation  being  determined  by  the  interaction  of  two  fac- 
tors— namely,  the  innate  constitutional  properties  of  the  proto- 
plasm and  adverse  environmental  conditions.  By  potential  lon- 
gevity is  meant  the  duration  of  life  which  might  be  expected 
under  an  ideal  environment.  The  average  specific  longevity, 
reckoned  from  birth,  is  greatest  in  the  most  civilized  communities 
and  reaches  at  present  the  length  of  forty-five  to  fifty  years. 
Quite  probably  the  advances  of  medical  knowledge,  especially  of 
preventive  medicine,  may  continue  to  increase  the  average  of  this 
expectation  of  life.  What  the  potential  longevity  of  man  would 
be  if  protected  from  all  accidents  and  disease  cannot  be  stated 
with  any  certainty,  but  on  the  basis  of  the  exceptional  cases  of 
longevity  reported  we  may  assume  that  it  would  exceed  one 
hundred  years.  The  most  authentic  of  the  cases  reported  of 
unusual  longevity  is  that  of  Thomas  Parr.  An  account  of  his 
life  and  the  results  of  a  postmortem  examination  by  Harvey 
are  given  in  Volume  III  of  the  "Philosophical  Transactions  of 
the  Royal  Society  of  London."  "He  died  after  he  had  out- 
lived nine  princes,  in  the  tenth  year  of  the  tenth  of  them,  at 
the  age  of  one  hundred  and  fifty-two  years  and  nine  months." 
The  immediate  cause  of  his  death  was  attributed  to  a  change 
of  food  and  air  and  habits  of  life,  as  he  was  brought  from  Shrop- 
shire to  London,  "where  he  fed  high  and  drunk  plentifully  of  the  best 
wines."*  With  reference  to  the  phenomenon  of  senescense  as  a  neces- 
sary attribute,  of  living  matter,  Weissmann  has  called  attention  to  the 
fact  that  inasmuch  as  the  species  continues  to  exist  after  the  in- 
dividual dies,  we  must  believe  that  the  protoplasm  of  the  repro- 
ductive elements  is  not  subject  to  natural  death,  but  has  a  self- 
perpetuating  metabolism  which  under  proper  conditions  makes  it 
immortal.  Weissmannf  designates  the  protoplasm  of  the  germ  cells 
as  germ-plasm,  that  of  the  rest  of  the  body  as  somatoplasm,  and 
inasmuch  as  the  former  continues  to  propagate  itself  indefinitely 
under  proper  conditions,  while  the  latter  has  a  limited  existence,  he 
concludes  that  originally  protoplasm  possessed  the  property  of 

*  A  picture  of  Parr  painted  by  van  Dyck  (1635)  is  exhibited  in  the  Royal 
Gallery,  Dresden,  No.  1032. 

f  Weifismann,  "Essays  upon  Heredity  and  Kindred  Biological  Prob- 
lems"; also  "Germ-plasm"  in  the  "Contemporary  Science  Series.  ' 


GROWTH    AND    SENESCENCE.  1021 

potential  immortality.  That  is,  barring  accidents,  disease,  etc.,  it 
was  capable  of  reproducing  itself  indefinitely.  He  assumes,  more- 
over, that  this  property  is  exhibited  at  present  in  many  of  the  sim- 
pler forms  of  life,  such  as  the  ameba.  This  latter  phase  of  his 
theory  has  been  the  subject  of  much  interesting  investigation,*  with 
some  contradictory  results,  but  it  has  been  shown  (Woodruff)  that 
a  specimen  of  paramecium,  isolated  and  kept  in  a  varying  culture- 
medium  during  three  and  a  half  years,  passed  through  2000 
divisions  at  an  average  rate  of  three  in  every  48  hours,  without  the 
appearance  of  signs  of  senility.  Later  experiments  by  the  same 
author  continued  over  five  years  indicated  that  the  single  cell 
originally  isolated  "possessed  the  potentiality  to  produce  similar 
cells  to  the  number  represented  by  2  raised  to  the  3029th  power,  or 
a  volume  of  protoplasm  approximately  equal  to  101000  times 
the  volume  of  the  earth."  Such  a  result  would  indicate  the  essen- 
tial correctness  of  Weissmann's  view.  One  of  the  most  significant 
and  definite  contributions  to  the  subject  of  growth  has  been  made  by 
Rubnerf  upon  the  basis  of  the  energy  factor.  His  estimates  were 
made  upon  data  collected  for  man  and  the  following  mammalia, 
horse,  cow,  sheep,  pig,  dog,  cat,  rabbit,  and  guinea-pig — and  they 
bring  out  the  surprising  fact  that  human  growth  constitutes  a  type 
of  its  own,  differing  greatly  from  that  shown  by  the  other  mammals 
named.  His  conclusions  are  expressed  in  two  general  laws  which  are 
founded  upon  calculations  made  upon  these  animals  in  the  first 
period  after  birth  during  the  time  necessary  for  doubling  the  weight 
of  the  animal :  First,  the  law  of  constant  energy  consumption.  During 
the  first  period  of  growth  the  total  amount  of  energy  necessary 
for  maintenance  (metabolism)  and  growth,  as  expressed  by  the 
heat  value  of  the  food  consumed,  is  the  same  for  all  mammals 
except  man.  To  form  one  kilogram  of  animal  weight  requires 
in  round  numbers  4808  Calories  in  food;  while  for  man  about  six 
times  this  amount  is  needed.  Since  the  several  mammals  con- 
sidered require  very  different  times  to  double  their  weight,  it 
follows  from  this  law  that  the  shorter  the  time  necessary  for  this 
result  the  more  intense  will  be  the  metabolism,  or,  expressed  in 
another  way,  the  rapidity  of  growth  is  proportional  to  the  intensity 
of  the  metabolic  processes.  Second,  the  law  of  the  constant  growth 
quotient.  In  all  the  mammals  considered,  with  the  exception  of 
man,  the  same  fractional  part  of  the  entire  food  energy  is  utilized 
for  growth.  This  fractional  portion  is  designated  as  the  "  growth- 
quotient,"  and  it  averages  34  per  cent.,  that  is  to  say,  for  every 

*  See  Maupas,  "Archives  de  zoologie  experimentale  et  generale,"  6,  165, 
1888;  Gotte,  "Ueber  den  Ursprung  des  Todes,"  1883;  Woodruff,  "American 
Naturalist,"  42,  500;  also  "Archiv  f.  Protistenkunde,"  21,  263,  1911. 

t  Rubner,  "Das  Problem  der  Lebensdauer,"  etc.,  Berlin,  1908.  - 


1022  THE    PHYSIOLOGY    OF    REPRODUCTION. 

1000  calories  of  food  340  calories  are  applied  to  growth.  In  man, 
on  the  contrary,  the  growth  quotient  is  only  5  per  cent.  This 
growth  quotient  is  a  specific  property  of  the  cell  and  a  charac- 
teristic of  youthfulness.  It  has  its  maximal  value  at  birth,  so 
far  as  extra-uterine  life  is  concerned,  and  then  sinks  slowly,  so 
that  at  maturity,  that  is,  at  the  end  of  the  growth  period,  it  becomes 
zero.  Thence  forward  the  energy  of  the  food  is  utilized  only  for 
the  maintenance  of  the  cells  and  for  the  work  they  perform,  none 
is  applied  to  growth.  Rubner  suggests  that  the  power  to  grow 
possessed  by  the  cells  of  the  young  organism  depends  upon  some 
special  mechanisms  of  a  chemical  nature,  that  is,  probably  certain 
special  chemical  complexes  which  are  responsible  for  the  "  growth 
tendency"  ( Wachstumstrieb) .  In  connection  with  this  growth 
energy  or  growth  tendency  it  will  be  remembered  that  in  the 
chapter  on  Internal  Secretion  evidence  was  given  that  in  early 
infancy  the  thymus  forms  apparently  an  internal  secretion  or 
hormone  which  controls  or  stimulates  the  process  of  growth,  and 
the  anterior  lobe  of  the  pituitary  gland  also  forms  an  internal 
secretion  which  has  a  similar  action.  It  will  be  noted  also  that 
both  of  these  glands  affect  mainly  the  growth  of  the  skeleton. 
The  increase  in  size  of  an  animal  is  normally  estimated  largely 
from  the  growth  of  the  skeleton,  and  Aron  has  shown  in  a  most 
interesting  way  that  the  growth  energy  resides  chiefly  in  this 
tissue.  According  to  this  author,  young  growing  dogs  if  given 
a  diet  insufficient  to  maintain  their  body  weight  will  still  continue 
to  grow,  since  the  skeleton  increases  in  size  at  the  expense  of  the 
other  tissues,  particularly  of  the  muscular  tissues.  The  growth 
tendency  in  the  skeletal  tissue  is  so  strong  that  other  tissues  are 
absorbed  to  furnish  the  necessary  material..  This  marked  growth 
tendency  of  the  skeleton,  as  we  have  just  said,  is  controlled  or 
stimulated  by  secretions  from  the  thymus  and  hypophysis  and 
possibly  from  other  sources.  The  fact  that  a  tissue  in  which  the 
growth  tendency  is  marked  will  live  at  the  expense  of  other 
tissues  finds  an  illustration  in  other  ways,  for  example,  in  the 
development  of  malignant  growths,  such  as  cancer  or  in  the  pro- 
cesses of  regeneration  in  the  lower  forms  of  life.  Stockhard  reports 
that  in  the  medusa,  when  unfed,  a  regenerating  tissue  may  grow 
rapidly  by  ieeding  on  the  old  body  tissues.  It  would  seem  that 
this  tendency  to  grow  must,  as  Rubner  suggests,  depend  upon 
some  peculiarity  in  the  chemical  structure  of  the  tissue  which 
exhibits  it.  Moreover,  there  is  considerable  evidence  that  for 
growth  to  take  place  certain  specific  building  materials  must  be 
furnished  in  the  diet.  As  stated  on  p.  911,  Osborne  and  Mendel 
have  shown  that  in  growing  rats  certain  proteins  supply  this 
material;  other  proteins  apparently  are  lacking  in  it,  but  may 


GROWTH    AND    SENESCENCE.  1023 

yield  material  adequate  for  maintenance  of  the  status  quo,  while 
still  others  are  inadequate  either  for  maintenance  or  growth. 
It  will  be  recalled  also  that  it  is  claimed  that  certain  specific 
nitrogenous  substances,  the  so-called  vitamines,  must  also  be 
furnished  in  the  food  for  special  metabolisms  of  the  body  that  are 
essential  to  life.  It  would  seem  possible  that  scientific  investiga- 
tions may  eventually  enable  us  to  control  or  even  prolong  the  period 
of  growth  through  dietary  treatment. 

After  the  period  of  maturity  has  been  reached  the  question 
arises  whether  the  subsequent  duration  of  life  can  be  foretold  or 
formulated  in  any  definite  way.  The  older  naturalists  conceived 
that  the  duration  of  mature  life  might  represent  a  definite  multiple 
of  the  period  of  youth.  According  to  Buffon  this  multiple  is  6  to 
7,  according  to  Flourens  it  is  5 — that  is,  the  mean  duration  of  life 
is  5  to  7  times  that  required  for  the  completion  of  growth.  The 
data  gathered  in  regard  to  the  average  duration  of  life  among 
different  animals  have  not  borne  out  these  suggestions,  and  Rubner 
discusses  the  matter  again  from  the  energy  standpoint.  He 
estimates  the  number  of  calories  of  food  which  are  required  for  each 
kilogram  of  body  weight  in  the  different  mammalia  from  the  end 
of  the  period  of  youth  to  the  end  of  life.  For  man  this  period  is 
estimated  at  sixty  years  (20  to  80).  On  this  basis  he  finds  that 
each  human  kilogram  requires  725,770  Calories,  while  for  the  other 
mammalia  for  which  data  are  accessible  an  average  of  only  191,600 
Calories  is  required,  and  the  figures  in  the  latter  animals  are  so 
close  as  almost  to  warrant  the  belief  that  the  same  amount  is 
required  by  each  animal  in  spite  of  the  great  variations  in  the 
duration  of  life.  It  follows  from  these  figures  that  the  human  cell 
is  characterized,  as  compared  with  that  of  the  other  mammalia, 
by  its  much  greater  total  capacity  for  obtaining  energy  from  the 
foodstuffs.  This  capacity,  the  property  of  assimilation,  implies 
chemical  changes  and  transformations  in  the  living  matter,  and 
the  fact  that  eventually  this  property  languishes  and  expires,  that 
is,  the  fact  that  there  is  such  a  thing  as  natural  or  physiological 
death,  means  that  the  somatic  protoplasm  is  capable  of  effecting 
only  a  limited  number  of  such  transformations.  In  man  a  greater 
number  is  possible  than  in  the  other  mammals,  and  among  the 
latter  the  number  is  practically  the  same,  but  in  the  smaller 
animals,  with  their  more  intense  metabolism,  the  series  is  com- 
pleted in  a  shorter  time  than  in  the  case  of  the  larger  animals. 
Rubner  states,  moreover,  that  if  a  cell,  the  yeast  cell,  for  example, 
by  artificial  means  is  forced  to  live  without  growing  and  multiply- 
ing it  dies  in  a  very  short  time.  In  some  way  the  processes  of 
growth  contain  the  very  source  of  the  maintenance  of  life.  The 
injurious  by-products  which  accompany  simple  metabolism  in  the 


1024  THE    PHYSIOLOGY    OF    REPRODUCTION. 

living  matter  are  in  some  way  obviated  or  neutralized  by  the 
growth  changes.  Rubner  suggests,  somewhat  in  the  line  of  Dar- 
win's theory  of  pangenesis  and  of  Weissmann's  theory  of  the  cause 
of  death  in  the  somatoplasm,  that  the  body-cells  give  off  certain 
molecular  complexes  which  are  necessary  to  the  growth  processes, 
and  these  complexes  are  taken  up  by  the  reproductive  cells.  After 
the  animal  has  reached  the  period  of  puberty,  of  reproductive 
power,  and  provision  is  thus  made  for  the  perpetuation  of  the 
species,  the  individual  organism  is  depleted  of  the  power  of  growth 
and  senescence  and  death  become  inevitable.  There  are  no  actual 
facts  at  present  to  support  such  a  view  and,  indeed,  it  is  at  variance 
with  prevalent  ideas  regarding  the  lack  of  direct  influence  of  the 
somatic  cells  upon  the  germ  cells. 


APPENDIX. 


PROTEINS  AND  THEIR  CLASSIFICATION. 

Definition  and  General  Structure. — Proteins  or  albumins  are  complex 
organic  compounds  containing  nitrogen  which,  although  differing  much  in 
their  composition,  are  related  in  their  properties.  They  are  formed  by 
living  matter,  and  occur  in  the  tissues  and  liquids  of  plants  and  animals, 
of  which  they  form  the  most  characteristic  constituent.  On  ultimate  analy- 
sis they  are  all  found  to  contain  carbon,  hydrogen,  oxygen,  and  nitrogen; 
most  of  them  contain  also  some  sulphur,  and  some,  in  addition,  phosphorus 
or  iron.  As  usually  obtained,  they  leave  also  some  ash  when  incinerated, 
showing  that  they  hold  in  combination  some  inorganic  salts.  Percentage 
analyses  of  the  most  common  proteins  of  the  body  show  that  the  above 
named  constituents  occur  in  the  following  proportions: 

Carbon 50     to  55     per  cent. 

Hydrogen 6.5  to    7.3   "       " 

Nitrogen 15     to  17.6   "       " 

Oxygen 19     to  24      "       " 

Sulphur 0.3  to    2.4   "       " 

The  clearest  insight  into  the  structure  of  the  protein  molecule  has  been 
obtained  by  a  study  of  its  decomposition  products.  When  submitted  to  the 
action  of  proteolytic  enzymes,  or  putrefaction,  or  acid  at  high  temperatures, 
the  large  molecules  split  into  a  number  of  simpler  bodies  in  consequence  of 
hydrolytic  cleavage.  These  end-products  are  very  numerous,  and,  while 
they  differ  somewhat  for  the  different  proteins,  yet  a  number  of  them  are 
the  same  or  similar  for  all  proteins.  The  great  variety  in  the  end-products  is 
an  indication  of  the  complexity  of  the  molecule,  while  their  similarity  is  proof 
that  the  various  proteins  are  all  built,  so  to  speak,  upon  a  common  plan,  by  the 
union  of  certain  groupings  which  may  be  more  numerous  in  one  protein  than 
in  another.  This  fact  becomes  evident  from  a  brief  consideration  of  the  prod- 
ucts obtained  by  hydrolytic  cleavage  with  acids.  The  groupings  represented 
by  the  following  compounds  may  be  supposed  to  exist  preformed  in  protein 
molecules,  some  possibly  containing  them  all,  some  only  a  portion  of  the 
list,  while  the  different  groups  vary  in  their  proportional  amounts  in  the 
various  proteins  (see  p.  799)'. 

Amino-adds. 

1.  Glycocoll  or  glycin  (amino-acetic  acid). 

2.  Alanin  (aminopropionic  acid). 

3.  Valin  (aminovalerianic  acid). 

4.  Leucin  (aminocaproic  acid). 

5.  Isoleucin  (aminocaproic  acid). 

6.  Norleucin  (aminocaproic  acid). 

7.  Lysin  (diaminocaproic  acid). 

8.  Serin  (oxyaminopropionic  acid). 

9.  Cystein  (aminothiopropionic  acid). 

10.  Phenylalanin  (phenylaminopropionic  acid). 

11.  Tyrosin  (oxy phenylaminopropionic  acid). 

12.  Tryptophan  (indolaminopropionic  acid). 

13.  Histidin  (imidazolaminopropionic  acid). 

14.  Arginin  (guamdinaminovalerianic  acid). 

15.  Aspartic  acid  (aminosuccinic  acid). 

16.  Glutaminic  acid  (aminoglutaric  acid). 

17.  Prolin  (pyrollidin-carboxylic  acid). 

18.  Oxyprolin  (oxypyrollidin-carboxylic  acid). 
65  1025 


APPENDIX. 

These  split  products  are  all  amino-acids,  some  of  them  belonging  to  the 
fatty  acid  (aliphatic)  series  of  carbon  compounds,  some  to  the  aromatic 
(carbocyclic)  series,  and  some  to  the  heterocyclic  (pyrrol,  indol)  series.  In 
what  may  be  considered  the  simplest  proteins  occurring  in  nature — namely, 
the  protamins  found  in  the  spermatozoa — only  from  four  to  six  of  these  groups 
occur,  while  in  some  of  the  more  familiar  proteins,  such  as  serum-albumin 
or  casein,  a  much  larger  number  is  found.  This  fact  is  illustrated  by  the 
following  table,  taken  from  Abderhalden,  which  shows  the  composition  of 
several  proteins  belonging  to  different  classes.  It  will  be  noted  that  except 
for  the  salmin  the  known  products  sum  up  to  less  than  100  per  cent.,  showing 
that  there  is  a  large  portion  of  the  molecule  as  yet  unknown. 

SERUM        SERUM       CASEIN.     SALMIN. 
ALBUMIN.  GLOBULIN. 

Glycin 0  3.5  0 

Alanin 2.7  2.2  0.9 

Valin present  1.0  4.3 

Leucin 20.0          18.7  10.5 

Prolin l.o  2.8  3.1          11.0 

Phenylalamin 3.1  3.8  3.2 

Glutaminic  acid 7.7  8.5  11.0 

Aspartic  acid 3.1  2.5  1.2 

Cystin 2.3  0.7  .065 

Serin 0.6  0.23          7.8 

Tyrosin 2.1  2.5  4.5 

Tryptoplian present    present  1.5 

Diaminotrioxydodecoic  acid ....  0.75 

Oxyprolin ....  0.25 

Lysin 5.80 

Arginin 4.84        87.4 

Histidin 2.59 

The  a-amino-acids  of  which  these  end-products  consist  all  contain  the 

I 
grouping  — C — NH2,  and   Fischer  has  shown  that  such  bodies  possess  the 

COOH 

property  of  combining  with  one  another  to  make  complex  molecules  containing, 
two,  three,  or  more  groups  of  amino-acids.  The  combination  takes  place 
with  the  elimination  of  water  formed  by  the  union  of  the  OH  of  the  carboxyl 
(COOH)  group  in  one  acid  and  the  H  of  the  amino  (NH2)  group  in  another. 
Thus,  two  molecules  of  amino-acetic  acid  (glycocoll)  may  be  made  to  unite  to 
form  a  compound,  glycylglycin,  as  follows: 

NH2CH2COOH  +  NH2CH2COOH  — H20  =  NH2CH2CONHCH2COOH. 

Glycocoll.  Glycocoll.  Glycylglycin. 

Compounds  of  this  kind  are  designated  by  Fischer  as  peptids.  When  formed 
from  the  union  of  two  amino-acids  they  are  known  as  dipeptids;  from  three, 
as  tripeptids,  etc.  The  more  complicated  compounds  of  this  sort,  the  poly- 
peptids,  begin  to  show  reactions  similar  to  those  of  the  proteins.  Some  of 
them  give  the  biuret  reaction,  some  are  acted  upon  and  split  by  proteolytic 
enzymes.  It  seems  justifiable,  therefore,  to  consider  proteins  as  essentially 
polypeptid  compounds  of  greater  or  less  complexity — that  is,  they  are  acid- 
amids  formed  by  the  union  of  a  number  of  a-amino-acid  compounds.  More 
than  a  hundred  of  these  artificial  polypeptids  have  been  thus  synthesized, 
one  of  the  most  complex,  an  octa-deca  peptid,  consisting  of  eighteen  mon- 
amino  acids,  fifteen  molecules  of  glycin,  and  three  of  leucin,  with  a  total  molec- 
ular weight  of  1213.  This  conception  of  the  structure  of  the  protein  molecule 
explains  a  number  of  their  general  characteristics — for  instance:  (1)  The 
fact  that  they  are  all  decomposed  and  yield  similar  products  under  the  inHuence 
of  proteolytic  enzymes  or  boiling  dilute  acid.  (2)  The  fact  that  the  proteins 


PROTEINS    AND    THEIR    CLASSIFICATION.  1027 

are  all  so  alike  in  their  general  properties  in  spite  of  the  great  differences  in 
the  complexity  of  their  molecular  structure.  (3)  The  fact  that  they  show 
both  basic  and  acid  characters.  (4)  The  fact  that  they  all  give  the  biuret 
reaction*  (see  below). 

In  addition  to  the  amino-acids  some  proteins — -egg-albumin,  for  example 
— yield  a  carbohydrate  body  upon  decomposition.  The  carbohydrate  ob- 
tained is  an  amino-sugar  compound,  usually  glucosamin,  C6H13NO5.  It  is 
detected  by  its  reducing  action  and  by  the  formation  of  an  osazone.  It  seems 
probable,  therefore,  that  some  of  the  proteins  at  least  contain  such  a  group- 
ing as  part  of  the  molecular  complex,  but  at  present  it  is  undetermined  how 
many  possess  this  peculiarity  of  structure. 

•  General  Reactions  of  the  Proteins. — It  is  evident  from  what  has  been 
said  in  the  preceding  paragraph  that  proteins  may  give  different  reactions 
according  to  the  kinds  of  groupings  contained  in  the  molecule.  The  reac- 
tions common  to  all  proteins  are  few  in  number,  the  most  certain  perhaps 
being  the  biuret  reaction,  the  hydrolysis  by  proteolytic  enzymes  or  putre- 
factive organisms,  and  the  nature  of  the  split  products  formed  by  these  latter 
hydrolyses  or  by  the  action  of  boiling  dilute  acids.  A  very  large  number 
of  reactions,  however,  have  been  described  which  hold  for  some  or  all  of 
the  proteins  usually  found  in  the  tissues  and  liquids  of  the  body.  These 
reactions  may  be  described  under  two  heads:  (1)  Precipitation  of  the  protein 
when  in  solution;  (2)  color  reactions. 

/.  Precipitants. — For  one  or  another  protein  the  following  reagents  cause 
precipitation : 

1.  The  addition  of  an  excess  of  alcohol. 

2.  Boiling  (heat  coagulation). 

3.  The  addition  of  mineral  acids, — e.  g.,  nitric  acid. 

4.  The  salts  of  the  heavy  metals, — e.  g.,  acetate  of  lead,  copper  sul- 

phate, etc. 

5.  Addition  of  neutral  salts  of  the  alkalies  to  a  greater  or  less  degree 

of  concentration, — e.  g.,  sodium  chlprid,  ammonium  sulphate. 

6.  Ferrocyanid  of  potassium  after  previous  acidification  by  acetic  acid. 

7.  Tannic  acid  after  previous  acidification  by  acetic  acid. 

8.  Phosphotungstic  or  phosphomolybdic  acid  in  the  presence  of  free 

mineral  acids. 

9    lodin  in  solution  in  potassium  iodid,  after  previous  acidification 
with  a  mineral  acid. 

10.  Picric  acid  in  solutions  acidified  by  organic  acids. 

11.  Trichloracetic  acid. 

This  list  might  be  extended  still  further,  but  it  comprises  the  precipi- 
tating reagents  that  are  ordinarily  used.  Some  of  them,  particularly  Nos. 
7,  8,  and  9,  give  reactions  in  solutions  containing  excessively  minute  traces 
of  protein. 

12.  Precipitins.     In  this  connection  a  brief  reference  may  be  made  to 

the  interesting  group  of  bodies  known  as  precipitins.  As  stated 
on  p.  425,  the  animal  organism  has  the  power,  when  foreign  cells 
are  injected  into  it,  of  forming  anti-bodies  by  a  specific  biological 
reaction.  It  has  been  discovered  that  anti-bodies  or,  as  they 
are  called  in  this  case,  precipitins  may  be  produced  in  the 
same  way  if  protein  solutions  or  solutions  of  animal  tissue  are  in- 
jected into  the  circulation.  Thus,  if  cows'  milk  be  injected  under 
the  skin  of  a  rabbit  there  will  be  produced  within  the  rabbit's 
blood  a  precipitin  which  is  capable  of  precipitating  the  casein  of 
cows'  milk,  although  it  may  have  no  action  on  the  milk  of  other 
animals.  In  the  same  way  any  given  foreign  protein,  when  injected 
under  the  skin  of  an  animal,  may  cause  the  production  of  a  pre- 
cipitin capable  of  precipitating  that  particular  protein  from  its 
solutions.  The  precipitin  is  not  absolutely  specific  for  the  protein 
used  to  produce  it,  but  nearly  so.  If  a  rabbit  is  immunized  with 

*  For  further  details,  see  Cohnheim,  "Chemie  der  Eiweisskorper,"  second 
edition,  1904;  or  Abderhalden,  "Lehrbuch  d.  physiol.  Chemie,"  1914;  and 
Rosenheim,  in  "Science  Progress,"  April  and  July,  1908. 


1028  APPENDIX. 

human  blood  a  precipitin  is  produced  in  the  animal's  blood 
which  causes  a  precipitate  when  mixed  with  human  blood  or 
with  that  of  some  of  the  higher  monkeys,  but  gives  no  reaction 
with  the  blood  of  other  mammals.  The  reaction  may  be  used, 
therefore,  in  a  measure  to  test  the  blood-relationship  of  different 
animals.*  It  has  been  suggested  that  the  reaction  may  also  be 
of  practical  importance  in  medicolegal  cases,  in  determining  whether 
a  given  blood-stain  is  or  is  not  human  blood.  For  such  a  pur- 
pose a  human  antiserum  is  first  produced  by  injecting  human 
serum  into  a  rabbit.  The  serum  of  the  rabbit  is  then  mixed  with 
an  extract  of  the  suspected  blood-stain  made  with  salt  solution; 
if  a  precipitate  forms  it  proves  that  the  blood  stain  is  human  blopd 
provided  the  possibility  of  its  being  monkey's  blood  is  excluded. 
Concerning  the  nature  of  the  precipitins,  little  is  known.  They 
combine  quantitatively  with  the  protein  precipitated  and  they 
are  inactivated  (hematosera)  by  a  temperature  of  70°  C.  Their 
reactions  are  not  sufficiently  specific  to  be  used  as  a  means  of  de- 
tecting or  distinguishing  closely  related  proteins. 
II.  The  Color  Reactions  of  Proteins. 

1.  The  biuret  reaction.  The  protein  solution  is  made  strongly  alkaline 
with  caustic  soda  or  potash  and  a  few  drops  of  a  dilute  solution  of 
copper  sulphate  are  added  carefully  so  as  to  avoid  an  excess.  A 
purple  color  is  obtained.  Some  proteins  (peptones)  give  a  red 
purple,  others  a  blue  purple.  If  only  a  blue  color,  without  any 
mixture  of  red,  is  obtained,  no  protein  is  present.  At  present 
this  reaction  gives  the  best  single  test  for  protein.  It  obtains 

its  name  from  the  fact  that  it  is  given  by  biuret  HN<QQtrTT2,  a 

compound  that  may  be  formed  by  heating  urea.  Two  molecules 
of  urea  give  off  a  molecule  of  ammonia  and  form  biuret. 

2.  The  ninhydrin  reaction.      Proteins  and  some  of  their  split  products 

give  a  blue  reaction  with  ninhydrin  (triketohydrindene  hydrate). 
This  reaction  is  especially  useful  in  testing  for  the  amino-acids  or 
peptids  when  the  hydrolysis  of  the  protein  has  gone  so  far  that  a 
biuret  reaction  is  no  longer  given.  One  to  two  drops  of  the  reagent 
are  added  to  1  c.c.  of  the  suspected  liquid,  and  the  solution  is  heated 
to  boiling.  On  cooling,  a  blue  color  develops  if  a-amino-acids  or  their 
derivatives  are  present. 

3.  The  Millon  reaction.     The  protein  solution  is  boiled  with  Millon's 

reagent.  The  solution  or  the  precipitate,  if  one  is  formed,  takes 
on  a  reddish  color,  which  varies  in  intensity  with  different  proteins. 
Millon's  reagent  consists  of  a  solution  of  mercuric  nitrate  in  nitric 
acid  containing  some  mercurous  nitrate.  This  reaction  is  supposed 
to  be  given  by  the  tyrosin  (oxy-aromatic)  grouping  in  the  protein 
molecule,  and  fails,  therefore,  with  those  proteins  in  which  tyrosin 
is  not  present. 

4.  Tyrosin  reagent.    Folin  and  Denis  f  report  a  new  color  reaction  for  the 

detection  of  phenol  compounds  which  may  be  used  for  the  quantita- 
tive determination  of  tyrosin,  The  reagent  consists  of  sodium  tungs- 
tate,  10  per  cent. ;  phosphomolybdic  acid,  2  per  cent. ;  and  phosphoric 
acid,  10  per  cent.  After  addition  of  the  reagent  the  blue  color  is 
developed  by  further  addition  of  an  excess  of  a  saturated  solution  of 
sodium  carbonate. 

5.  The  xanthoproteic  reaction.     Nitric  acid  is  added  to  strong  acid 

reaction  and  the  solution  is  then  boiled.  After  cooling,  ammonia 
is  added.  The  ammonia  causes  the  development  of  a  deep-yellow 
color  if  protein  is  present.  This  reaction  is  supposed  to  be  due 
to  the  presence  in  the  molecule  of  the  groupings  belonging  to  the 
aromatic  series. 

*  For  many  interesting  experiments  and  the  literature,  seeNuttall,  '  'Blood 
Immunity  and  Relationship,"  Cambridge,  1904. 

t  Folin  and  Denis,  "Journal  of  Biological  Chemistry,"  12,  240,  1912. 


PROTEINS    AND    THEIR    CLASSIFICATION.  1029 

6.  Adamkiewicz's  reaction.     A  mixture  is  made  of  one  volume  of  con- 

centrated sulphuric  and  two  volumes  of  glacial  acetic  acid;  if  the 
protein  solution  is  added  to  this  mixture  and  warmed  a  reddish- 
violet  color  is  obtained.  According  to  Hopkins  and  Cole,  the  reac- 
tion depends  upon  the  presence  of  glyoxylic  acid  in  the  acetic  acid, 
but  according  to  Homer  it  is  really  a  formaldehyd  reaction.  The 
action  of  the  sulphuric  acid  upon  the  glyoxylic  acid  produces  some 
formaldehyd.  This  reaction  seems  to  be  due  to  the  tryptophan 
grouping  in  the  protein  molecule. 

7.  Liebermann's  reaction.     Dry  protein  purified  with  alcohol  and  ether 

gives  a  blue  color  upon  boiling  with  strong  hydrochloric  acid. 

8.  The  lead  sulphid  reaction.     The  protein  solution  is  boiled  with  a 

solution  of  a  lead  salt  made  strongly  alkaline  with  soda  or  potash. 
A  black  precipitate  or  black  or  brown  coloration  results,  according 
to  the  amount  of  protein.  The  color  is  due  to  the  splitting  off  of 
sulphur  and  formation  of  lead  sulphid.  It  is  given,  therefore,  by 
the  sulphur-containing  groups  in  the  protein  molecule. 

9.  The  Molisch  reaction.     A  few  drops  of  an  alcoholic  solution  of  a- 

naphthol  are  added  to  the  protein  solution  and  then  strong  sul- 
phuric acid.  A  violet  color  is  obtained.  This  reaction  is  given 
by  the  carbohydrate  grouping  in  the  protein  molecule.  The  strong 
acid  forms  furfural  from  this  group,  which  then  reacts  with  the  naph- 
thol.  The  reaction  is  not  given  by  those  proteins  that  do  not  con- 
tain a  carbohydrate  group. 

Classification  of  the  Proteins. — No  classification  of  the  proteins  has 
been  proposed  which  is  entirely  satisfactory.  Eventually  a  classification 
may  be  obtained  based  upon  the  chemical  structure  of  the  various  proteins, 
the  number  and  arrangement  of  the  constituent  amino  bodies,  but  our  know- 
ledge at  present  is  much  too  incomplete  for  this  purpose.  We  must  be  con- 
tent with  a  less  satisfactory  system  based  in  part  upon  empirical  reactions 
which  have  gradually  been  recognized  in  the  course  of  physiological  inves- 
tigations. 

In  the  following  classification  the  recommendations  are  followed  of  the 
Joint  Committee  on  Protein  Nomenclature  appointed  by  the  American  Physi- 
ological Society  and  the  American  Society  of  Biological  Chemists  ("  American 
Journal  of  Physiology,  Proc.  Physiol.  Soc.,"  vol.  xxi.,  1908): 

f  Albumins. 
I.  Simple  proteins  (protein  sub- 


atives  on  hydrolysis). 


Histons. 


Protamins. 

II..  Conjugated      proteins       (sub-   f  Glycoproteins. 
stances  which  contain  the  pro-   j  Nucleoproteins. 
tein  molecule  united  to  some  -j  Hemoglobins  (chromoproteins), 
other    molecule   or  molecules   |  Phosphoproteins. 
otherwise  than  as  a  salt).  [  Lecithopoteins. 

'  Primary    protein    derivatives  "] 

(formed  through  hydrolytic    j  Proteans. 
changes   which   cause   only    ^  Metaproteins. 
slight  alterations  of  the  pro-   I  Coagulated  proteins, 
tein  molecule).  J 


Ill.  Derived  proteins 


Secondary  protein  deriva-  "1  -p  , 
tives.  (Products  of  further  ro1 
hydrolytic  cleavage  of  the 


y  avag     o 

protein  molecule.) 


The  Albumins.  —  In  addition  to  the  albumins  found  in  the  cellular  tis- 
sues, the  cell  albumins,  the  conspicuous  examples  of  this  group  are  serum- 


1030  APPENDIX. 

albumin,  milk-albumin  (lactalbumin) ,  and  egg-albumin  (ovalbumin).  They 
are  characterized  as  a  class  by  the  fact  that  they  are  coagulable  by  heat  in 
solutions  with  a  neutral  or  acid  reaction,  and  are  soluble  in  water  free  from 
salts.  In  accordance  with  the  latter  part  of  this  definition  they  are  not 
precipitated  by  dialysis.  They  are  precipitated  from  their  solutions  with 
more  difficulty  by  saturation  with  neutral  salts,  ammonium  sulphate,  than 
the  globulins  with  which  they  are  usually  associated.  Empirically,  as  regards 
the  liquids  of  the  body,  it  is  stated  that  they  require  more  than  half  saturation 
with  ammonium  sulphate  for  precipitation  (see  section  on  Blood).  All 
three  albumins  referred  to  here  may  be  obtained  in  crystallized  form.  They 
are  not  precipitated  by  saturation  with  sodium  chlorid  or  magnesium  sul- 

Ehate  unless  the  solution  is  made  acid.  They  are  rich  in  sulphur,  containing 
*om  1.6  to  2.2  per  cent.,  and  on  hydrolysis  they  yield  no  glycocoll. 

The  Globulins. — Proteins  belonging  to  this  group  are  found  in  the  cell 
tissues  together  with  albumins.  The  forms  that  have  been  most  studied 
are  serum-globulin  (paraglobulin)  and  fibrinogen  (blood,  lymph,  and  transu- 
data),  milk-globulin  (lactoglobulin),  and  egg-globulin.  As  contrasted  with 
the  albumins,  they  are  coagulable  by  heat,  but  are  insoluble  in  pure  water. 
They  are  readily  soluble  in  dilute  solutions  of  neutral  salts,  that  is,  salts  of 
strong  bases  with  strong  acids.  In  consequence  of  their  insolubility  in  water 
they  are  precipitated  by  dialysis.  This  reaction  is  not  distinctive,  however, 
as  the  precipitation  is  not  coniplete.  Some  of  the  so-called  globulin  remains  in 
solution  after  the  salts  have  been  removed  as  completely  as  possible  by 
dialysis.  They  are  also  precipitated  partially  from  their  dilute  solutions  by 
the  addition  of  weak  acids  or  by  a  stream  of  carbon  dioxid.  Practically  they 
are  isolated  from  accompanying  albumins  by  precipitation  with  neutral  salts. 
In  neutral  solutions  the  globulins  are  completely  precipitated  by  saturation 
with  magnesium  sulphate  or  half  saturation  with  ammonium  sulphate.  In 
the  blood  several  different  forms  of  globulin  are  distinguished  by  the  degree 
of  saturation  with  ammonium  sulphate  necessary  for  their  precipitation  (see 
Blood).  The  separations  made  by  this  method  are  not,  however,  satisfac- 
tory. Nor,  indeed,  is  the  separation  between  globulins  and  albumins  alto- 
gether satisfactory.  It  would  seem  that  these  proteins  are  so  closely  related 
that  distinctive  reactions  are  difficult  to  obtain  on  account  of  the  existence 
of  forms  intermediate  between  the  extremes  that  are  used  as  types. 

The  Glutelins. — These  proteins  occur  in  abundance  in  the  seeds  of 
cereals.  They  are  insoluble  in  all  neutral  solvents,  but  are  readily  dissolved 
by  very  dilute  acids  or  alkalies. 

Alcohol-soluble  Proteins  (Prolamines). — Found  in  quantity  in  cereals, 
but  not  in  other  seeds.  They  are  soluble  in  alcohol  (70-80  per  cent.),  but 
insoluble  in  water  or  in  absolute  alcohol.  Gliadin  of  wheat  and  rye  and  hor- 
dein  of  barley  are  examples.  On  hydrolysis  these  proteins  give  a  very  large 
percentage  of  glutaminic  acid  (20  to  37  per  cent.)  and  from  20  to  30  per  cent, 
of  their  nitrogen  is  given  off  as  ammonia.* 

Albuminoids. — Simple  proteins  which  are  characterized  by  great  in- 
solubility in  all  neutral  solvents.  They  form  the  principle  constituent  of 
the  skeletal  tissues  and  connective  tissues,  epidermis,  hairs,  etc.,  including 
such  members  as  elastin,  keratin,  and  collagen.  Physiologically  it  has  been 
found  that  gelatin,  a  derivative  of  collagen,  does  not  suffice  for  the  construction 
of  living  protein,  and  cannot  be  used  in  place  of  the  other  proteins  to  main- 
tain nitrogen  equilibrium.  This  peculiarity  seems  to  be  due  to  the  absence 
of  certain  necessary  amino-acids  in  its  molecule.  (See  p.  910.) 

Protamins  and  Histons. — The  histons  are  defined  as  being  soluble  in 
water  and  insoluble  in  very  dilute  ammonia.  They  yield  precipitates  with 
solutions  of  other  proteins  and  give  a  coagulum  on  heating.  Protamins 
are  soluble  in  water,  not  coagulated  by  heating,  and,  like  the  histons,  have 
the  property  of  precipitating  other  proteins  in  aqueous  solutions.  They 
possess  strong  basic  properties  and  form  stable  salts.  The  protamins  have 
been  obtained  (Miescher-Kossel)  from  the  heads  of  the  spermatozoa  in  fishes, 
in  which  they  exist  in  combination  with  nucleic  acid.  They  differ  considerably 

*  For  description  of  this  and  other  vegetable  proteins,  see  Osborne, 
"Science,"  Oct.  2,  1908. 


PROTEINS    AND    THEIR    CLASSIFICATION.  1031 

in  the  spermatozoa  of  different  animals,  and  are,  therefore,  designated  accord- 
ing to  the  zoological  name  of  the  fish  from  which  they  arise,  as  salmin,  sturin, 
clupein,  scombrin,  etc.  They  show  a  biuret  reaction,  but  in  most  cases  fail  to 
give  Millon's  reaction.  On  hydrolysis  they  give  split  products,  which  consist 
chiefly  of  the  so-called  diamino-bodies  (arginin,  histidin,  lysin)  rather  than  the 
monamino-acids.  Some  of  the  latter  may  occur,  however,  such  as  alanin, 
serin,  aminovalerianic  or  a-pyrrollidin-carboxylic  acid.  The  protamins  all  give 
an  alkaline  reaction,  form  salts  with  acids,  and  are  precipitated  easily.  Their 
molecular  structure  is  relatively  simple.  Salmin  is  given  the  formula  C30H57- 
C17H6.  The  molecule  contains  no  sulphur  and  is  characterized  also  by  its 
large  percentage  of  nitrogen.  Protamin  must  be  regarded  as  the  simplest 
form  of  protein  occurring  normally  in  the  animal  body,  a  protein  in  which 
many  of  the  groupings,  such  as  cystin,  tyrosin,  carbohydrates,  found  in  the 
usual  protein  molecule  are  entirely  lacking  and  in  which  the  basic  groupings 
(arginin)  predominate.  The  histons  form  a  series  of  compounds  intermediate 
in  many  ways  between  the  protamins  and  the  usual  proteins.  The  reaction 
usually  considered  as  characteristic  of  the  class  is  that  they  are  precipitated 
by  ammonia.  They  are  precipitated  also  by  the  alkaloidal  reagents — e.  g., 
phosphotungstic  acid — in  neutral  solutions.  Ordinary  proteins  give  a  pre- 
cipitate with  these  reagents  only  in  acid  solutions,  while  the  protamins  give 
one  even  in  alkaline  solutions.  Protamins,  histons,  and  the  usual  proteins 
form  a  series,  therefore,  in  which  the  basic  reaction  is  less  and  less  marked. 
The  best  known  of  the  histons  is  the  globin  obtained  from  hemoglobin  ;  an- 
other form  has  been  obtained  from  the  nucleohiston  in  the  white  corpuscles, 
from  the  spermatozoa  of  mackerel  (scombron),  codfish  (gadushiston),  sea- 
urchin  (arbacin),  and  frog  (lotahiston).  They  do  not  occur  free  in  the  liquids 
or  tissues  of  the  body,  but  in  combination,  as  in  the  case  of  hemoglobin. 
They  give  the  biuret  reaction,  a  faint  Millon  reaction,  and  also  respond  to  the 
tests  for  sulphur.  The  products  obtained  by  their  hydrolytic  cleavage  are 
much  more  numerous  than  in  the  case  of  the  protamins — a  fact  which  would 
indicate  that  their  molecular  structure  is  correspondingly  more  complex. 

The  Conjugated  Proteins. — The  chromoproteins  or  hemoglobins  may  be 
defined  as  consisting  of  a  simple  protein  in  combination  with  a  pigment 
grouping,  such  as  occurs  in  the  case  of  hemoglobin.  A  number  of  such  com- 
pounds are  known — hemoglobin,  hemocyanin,  hemerythrin,  chlorocruorin — 
all  characterized  physiologically  by  the  fact  that  they  serve  to  transport 
oxygen  from  the  air  or  water  to  the  tissues.  On  boiling,  heating  with  alkalies 
or  acids,  etc.,  they  readily  decompose  into  their  constituent  parts  (see  Blood). 
Glycoproteins  are  compounds  of  a  carbohydrate  group  with  a  simple  protein. 
Numerous  bodies  have  been  put  in  this  class;  some  of  them  contain  phos- 
phorus (phosphoglucoproteins).  Those  free  from  phosphorus  fall  into  two 
divisions:  one,  the  mucins,  which  on  decomposition  yield  the  carbohydrate 
group  in  the  form  of  an  amino-sugar  (glucosamin),  and  one,  the  chondropro- 
teins,  found  in  the  connective  tissues  and  in  the  pathological  substance  known 
as  amyloid,  which  yield  their  carbohydrate  group  in  the  form  of  chondroitin- 
sulphuric  acid  (C18H27NSO17).  True  mucin  is  obtained  from  the  secretion 
of  the  salivary  glands  and  the  mucous  glands  of  the  various  mucous  mem- 
branes. The  nudeoproteins  constitute  the  most  interesting  of  the  group 
of  compound  proteins.  They  are  recognized  as  forming  an  important  con- 
stituent of  the  cell  nuclei.  They  may  be  defined  as  consisting  of  a  compound 
of  simple  protein  with  a  nucleic  acid.  In  the  nuclei  (head)  of  spermatozoa 
the  compound,  in  some  cases  at  least  (fishes),  contains  a  nucleic  acid  and  a 
protamin.  In  other  cases  the  protein  constituent  is  more  complex.  On 
digestion  with  pepsin-hydrochloric  acid  the  more  complex  nudeoproteins 
split,  with  the  formation,  first,  of  a  protein  substance  and  a  simpler  nucleo- 
protein,  richer  in  phosphorus  and  designated  as  a  nuclein.  On  further 
decomposition  this  latter  yields  a  nucleic  acid.  Nucleic  acid  is,  therefore, 
the  characteristic  constituent,  and  a  number  of  different  forms  have  been 
described,  all  rich  in  phosphorus,  such  as  thymonucleic  acid,  salmonnucleic 
acid,  guanylic  acid,  etc.  Levene  and  Jacobs  have  shown  that  the  various 
nucleic  acids  are  constructed  on  a  general  type  which  consists  of  a  phosphoric 
acid  group  linked  to  a  nitrogenous  base  by  means  of  a  carbohydrate  group. 
This  latter  group  is  d  ribose,  one  of  the  pentoses.  Compounds  of  this  type 


1032  APPENDIX. 

they  propose  to  designate  as  nuclotides.  When  the  phosphoric  acid  is  split 
off  a  compound  of  the  carbohydrate  and  the  nitrogenous  base  is  left,  and  on 
further  hydrolysis  the  carbohydrate  may  be  split  off  and  various  nitrogenous 
substances  be  formed,  such  as  purin  bases  or  pyrimidin  derivatives.  These 
final  decomposition  products  are  characteristic  of  the  true  nucleoproteins  as 
distinguished  from  the  phosphorus-containing  proteins,  the  nucleo-albumins 
or  phosphoproteins,  such  as  casein.  The  percentage  of  phosphorus  in  the 
nucleoproteins  varies,  according  to  the  complexity  of  the  molecule,  between 
0.5  and  1.6  per  cent. 

The  lecithoproteins  consist  of  compounds  of  the  protein  molecule  with 
lecithin  (lecithans,  phosphatids),  while  the  phosphoproteins  are  compounds 
of  the  protein  molecule  with  some,  as  yet  undefined,  phosphorus-containing 
substance  other  than  a  nucleic  acid  or  lecithin.  This  group  contains  such 
proteins  as  the  vitellin  of  the  yolk  and  casein  of  milk,  which  were  formerly 
designated  as  nucleo-albumins. 

The  Derived  Proteins. — Under  this  designation  are  included  products 
derived  from  the  simple  proteins  by  hydrolysis.  When  the  hydrolytic  change 
involves  only  a  slight  change  in  the  protein  molecule  we  have  what  are  known 
as  primary  derivatives,  of  which  three  groups  are  made:  (1)  Proteans,  cer- 
tain insoluble  products  which  result  from  the  incipient  action  of  water, 
enzymes,  or  very  dilute  acids.  (2)  Metaproteins,  products  which  result  from 
the  further  action  of  acids  or  alkalies,  by  means  of  which  the  protein  is  con- 
verted into  a  form  soluble  in  weak  acids  or  alkalies,  but  precipitated  on  neu- 
tralization. This  group  includes  what  was  formerly  designated  as  acid  or 
alkali  albumin.  (3)  Coagulated  protein — insoluble  products  formed  by 
the  action  of  heat,  alcohol,  etc. 

If  the  hydrolysis  proceeds  further,  certain  cleavage  products  result  which 
are  simpler  than  these  just  named,  but  are  more  complex  than  the  final 
products  of  complete  hydrolysis  (amino-acids).  These  intermediate  cleavage 
products  are  grouped  under  the  term  secondary  derivatives  and  include: 
(1)  Proteoses,  products  which  are  soluble  in  water,  not  coagulated  by  heat, 
and  are  completely  precipitated  by  saturation  with  ammonium  sulphate  or 
zinc  sulphate.  (2)  Peptones,  products  which  are  soluble  in  water,  are  not 
coagulated  by  heat,  and  are  not  precipitated'  by  saturation  with  ammonium 
sulphate.  (3)  Peptids,  products  which  consist  of  two  or  more  amino-acids 
in  which  the  carboxyl  group  of  one  is  united  with  the  amino  group  of  an- 
other, with  the  elimination  of  a  molecule  of  water.  The  peptones  probably 
are  simply  polypeptids  or  mixtures  of  polypeptids. 

DIFFUSION  AND  OSMOSIS. 

In  recent  years  the  physical  conceptions  of  the  nature  of  the  processes 
of  diffusion  and  osmosis  have  changed  considerably.  As  these  newer  concep- 
tions have  entered  largely  into  current  medical  literature,  it  seems  advis- 
able to  give  a  brief  description  of  them  for  the  use  of  those  students  of  phys- 
iology who  may  be  unacquainted  with  the  modern  nomenclature.  The 
very  limited  space  that  can  be  devoted  to  the  subject  forbids  anything  more 
than  a  condensed  elementary  presentation.  For  fuller  information  refer- 
ence must  be  made  to  special  treatises.* 

Diffusion,  Dialysis,  and  Osmosis. — When  two  gases  are  brought  into 
contact  a  homogeneous  mixture  of  the  two  is  soon  obtained.  This  inter- 
penetration  of  the  gases  is  spoken  of  as  diffusion,  and  it  is  due  to  the  con- 
tinual movements  of  the  gaseous  molecules  to  and  fro  within  the  limits  of 
the  confining  space.  So  also  when  two  miscible  liquids  or  solutions  are 
brought  into  contact  a  diffusion  occurs  for  the  same  reason,  the  movements 
of  the  molecules  finally  effecting  a  homogeneous  mixture.  If  the  two  liquids 
happen  to  be  separated  by  a  membrane  diffusion  will  still  occur,  provided 
the  membrane  is  permeable  to  the  liquid  molecules,  and  in  time  the  liquids 

*  Consult  Bayliss,  "Principles  of  General  Physiology,"  1915;  McClendon, 
"Physical  Chemistry  of  Vital  Phenomena,"  1917;  Hober,  " Physikalische 
Chemie  d.  Zelle  u.  d.  Gewebe." 


PROTEINS    AND    THEIR    CLASSIFICATION.  1Q33 

on  the  two  sides  will  be  mixtures  having  a  uniform  composition.  Not  only 
water  molecules,  but  the  molecules  of  many  substances  in  solution,  such 
as  sugar,  may  pass  to  and  fro  through  membranes,  so  that  two  liquids  sepa- 
rated from  each  other  by  an  intervening  membrane  and  originally  unlike 
in  composition  may  finally,  by  the  act  of  diffusion,  come  to  have  the  same 
composition.  Diffusion  of  this  kind  through  a  membrane  is  frequentlv 
spoken  of  as  dialysis  or  osmosis.  In  the  body  we  deal  with  aqueous  solu- 
tions of  various  substances  that  are  separated  from  each  other  by  living 
membranes,  such  as  the  walls  of  the  blood  capillaries  or  of  the  alimentary 
canal,  and  the  laws  of  diffusion  through  membranes  are  of  immediate  im- 
portance in  explaining  the  passage  of  water  and  dissolved  substances  through 
these  living  septa.  In  aqueous  solutions  such  as  we  have  in  the  body  we  must 
take  into  account  the  movements  of  the  molecules  of  the  solvent,  water, 
as  well  as  of  the  substances  dissolved.  These  latter  may  have  different  de- 
grees of  diffusibility  as  compared  with  one  another  or  with  the  water  mole- 
cules, and  it  frequently  happens  that  a  membrane  that  is  permeable  to 
water  molecules  is  less  permeable  or  even  impermeable  to  the  molecules  of 
the  substances  in  solution.  For  this  reason  the  diffusion  stream  of  water 
and  of  the  dissolved  substances  may  be  differentiated,  as  it  were,  to  a  greater 
or  less  extent.  The  energy  or  force  responsible  for  the  diffusion  of  molecules 
in  solution  is  an  outcome  of  the  intrinsic  energy  of  the  molecules  which  keeps 
them  hi  movement.  This  energy  is  designated  as  osmotic  pressure.  It  can 
be  measured  accurately,  although  its  exact  nature  is  not  understood. 

Osmotic  Pressure. — If  we  imagine  two  masses  of  water  separated  by 
a  permeable  membrane,  we  can  readily  understand  that  as  many  water  mole- 
cules will  pass  through  from  one  side  as  from  the  other;  the  two  streams, 
in  fact,  will  neutralize  each  other,  and  the  volumes  of  the  two  masses  pi 
water  will  remain  unchanged.  The  movement  of  the  water  molecules  in 
this  case  is  not  actually  observed,  but  it  is  assumed  to  take  place  on  the 
theory  that  the  liquid  molecules  are  continually  in  motion  and  that  the 
membrane,  being  permeable,  offers  no  obstacle  to  their  movements.  If. 
now,  on  one  side  of  the  membrane  we  place  a  solution  of  some  crystalloid 
substance,  such  as  common  salt,  and  on  the  other  side  pure  water,  then  it 
will  be  found  that  an  excess  of  water  will  pass  from  the  water  side  to  the 
side  containing  the  solution.  In  the  older  terminology  it  was  said  that  the 
salt  attracted  this  water,  but  in  the  newer  theories  the  same  fact  is  expressed 
by  saying  that  the  salt  in  solution  exerts  a  certain  osmotic  pressure,  in  conse- 
quence of  which  more  water  flows  from  the  water  side  to  the  side  of  the 
solution  than  in  the  reverse  direction.  As  a  matter  of  experiment  it  is  found 
that  the  osmotic  pressure  varies  with  the  amount  of  the  substance  hi  solu- 
tion. If  in  experiments  of  this  kind  a  semipermeable  membrane  is  chosen 
— that  is,  a  membrane  that  is  permeable  to  the  water  molecules,  but  not  to 
the  molecules  of  the  substance  in  solution — the  stream  of  water  to  the  side 
of  the  crystalloid  will  continue  until  the  hydrostatic  pressure  on  this  side 
reaches  a  certain  point,  and  the  hydrostatic  pressure  thus  caused  may  be 
taken  as  a  measure  of  the  osmotic  pressure  exerted  b"  the  substance  in  solu- 
tion. Under  these  conditions  it  can  be  shown  that  the  osmotic  pressure 
is  proportional  to  the  concentration  of  the  solution,  or,  in  other  words,  to 
the  number  of  molecules  (and  ions)  of  the  crystalloid  hi  solution.  As  a 
matter  of  fact,  most  of  the  membranes  that  we  have  to  deal  with  in  the 
body  are  only  approximately  semipermeable — that  is,  while  they  are  readily 
permeable  to  water  molecules,  they  are  also  permeable,  although  with  more 
or  less  difficulty,  to  the  substances  hi  solution.  In  such  cases  we  get  an 
osmotic  stream  of  water  to  the  side  of  the  dissolved  crystalloid,  but  at  the 
same  time  the  molecules  of  the  latter  pass  to  some  extent  through  the  mem- 
brane, by  diffusion,  to  the  other  side.  In  course  of  time,  therefore,  the 
dissolved  crystalloid  will  be  equally  distributed  on  the  two  sides  of  the  mem- 
brane, the  osmotic  pressure  on  both  sides  will  become  equal,  and  osmosis 
of  the  water  will  cease  to  be  apparent,  since  it  is  equal  in  the  two  directions. 
All  substances  in  true  solution  are  capable  of  exerting  osmotic  pressure, 
and  the  important  discovery  has  been  made  that  the  osmotic  pressure,  meas- 
ured in  terms  of  atmospheres  or  the  pressure  of  a  column  of  water  or  mer- 
cury, is  equal  to  the  gas  pressure  that  would  be  exerted  by  a  number  of 


1034  APPENDIX. 

molecules  of  gas  equal  to  that  of  the  crystalloid  in  solution,  if  confined  within 
the  same  space  and  kept  at  the  same  temperature.*  A  perfectly  satisfactory 
explanation  of  the  nature  of  osmotic  pressure  has  not  been  furnished.  We 
must  be  content  to  use  the  term  to  express  the  fact  described.  It  is  a  matter 
of  great  importance  to  measure  the  osmotic  pressures  of  various  solutions. 
As  was  stated  above,  this  measurement  can  be  made  for  any  solution  pro- 
vided a  really  semipermeable  membrane  is  constructed.  As  a  matter  of 
fact,  however,  the  use  of  such  membranes  has  not  been  general.  In  actual 
experiments  other  methods  have  been  employed,  and  a  brief  statement 
of  a  theoretical  and  a  practical  method  of  arriving  at  the  value  of  osmotic 
pressures  may  be  of  service  in  further  illustrating  the  meaning  of  the  term. 
Before  stating  these  methods  it  becomes  necessary  to  define  two  terms — 
namely,  electrolytes  and  gram-molecular  solutions — that  are  much  used 
in  this  connection. 

Electrolytes. — The  molecules  of  many  substances  when  brought  into 
a  state  of  solution  are  believed  to  be  dissociated  into  two  or  more  parts, 
known  as  ions.  The  completeness  of  the  dissociation  varies  with  the  sub- 
stance used,  and  for  any  one  substance  with  the  degree  of  dilution.  Roughly 
speaking,  the  greater  the  dilution,  the  more  nearly  complete  is  the  dissocia- 
tion. The  ions  liberated  by  this  act  of  dissociation  carry  an  electrical  charge 
and  when  an  electrical  current  is  led  into  the  solution  it  is  conducted  in  a 
definite  direction  by  the  movements  or  migration  of  the  charged  ions.  The 
molecules  of  perfectly  pure  water  undergo  almost  no  dissociation,  and  water, 
therefore,  does  not  appreciably  conduct  the  electrical  current.  If  some 
NaCl  is  dissolved  in  water,  a  certain  number  of  its  molecules  become  dis- 
sociated into  a  Na  ion  charged  positively  with  electricity  and  a  Cl  ion  charged 
negatively,  and  the  solution  becomes  a  conductor  of  the  electrical  current. 
Substances  that  exhibit  this  property  of  dissociation  into  electrically-charged 
ions  are  known  as  electrolytes,  to  distinguish  them  from  other  soluble  sub- 
stances, such  as  sugar,  that  do  not  dissociate  in  solution  and,  therefore,  do  not 
conduct  the  electrical  current.  Speaking  generally,  it  may  be  said  that  all 
salts,  bases,  and  acids  belong  to  the  group  of  electrolytes.  The  conception  of 
electrolytes  is  very  important  for  the  reason  that  the  act  of  dissociation  ob- 
viously increases  the  number  of  particles  moving  in  the  solution  and  thereby 
increases  the  osmotic  pressure,  since  it  has  been  found  experimentally  that,  so 
far  as  osmotic  pressures  are  concerned,  an  ion  plays  the  same  part  as  a  mole- 
cule. It  follows,  therefore,  that  the  osmotic  pressure  of  any  given  electrolyte 
in  solution  is  increased  in  proportion  to  the  degree  to  which  it  is  dissociated. 
As  the  liquids  of  the  body  contain  electrolytes  in  solution  it  becomes  neces-' 
sary,  in  estimating  their  osmotic  pressure,  to  take  this  fact  into  consideration. 

Gram-molecular  Solutions. — The  concentration  of  a  given  substance 
in  solution  may  be  stated  by  the  usual  method  of  percentages,  but  from  the 
standpoint  of  osmotic  pressure  a  more  convenient  method  is  the  use  of  the 
unit  known  as  a  gram-molecular  solution.  A  gram-molecule  of  any  sub- 
stance is  a  quantity  in  grams  of  the  substance  equal  to  its  molecular  weight, 
while  a  gram-molecular  solution  is  one  containing  a  gram-molecule  of  the 
substance  to  a  liter  of  the  solution.  Thus,  a  gram-molecular  solution  of 
sodium  chlorid  is  one  containing  58.5  gms.  (Na,  23;  Cl,  35.5)  of  the  salt  to 
a  liter,  while  a  gram-molecular  solution  of  cane-sugar  contains  342  gms. 
(CujHjjgOn)  to  a  liter.  Similarly  a  gram-molecule  of  H  is  2  gms.  by  weight 
of  this  gas,  and  if  this  weight  of  H  were  compressed  to  the  volume  of  a  litei 
it  would  be  comparable  to  a  gram-molecular  solution.  Since  the  weight 
of  a  molecule  of  H  is  to  the  weight  of  a  molecule  of  cane-sugar  as  2  is  to 
342,  it  follows  that  a  liter  containing  2  gms.  of  H  has  the  same  number  of 

*  The  interesting  researches  of  Morse  and  Frazer  ("  The  American  Chemi- 
cal Journal,"  34,  1,  1905),  who  have  succeeded  in  making  semipermeable 
membranes  in  such  a  form  as  may  be  used  for  determining  directly  the  os- 
motic pressures  of  concentrated  (normal)  solutions,  have  shown  that  this 
law  is  not  accurately  stated.  The  actual  pressure  is  that  which  would  be 
exerted  if  the  particles  in  solution  were  gasified  at  the  same  temperature  and 
kept  to  the  volume  of  the  pure  solvent  used  (water),  instead  of  the  volume 
of  the  entire  solution. 


PROTEINS    AND    THEIR    CLASSIFICATION.  1035 

molecules  of  H  in  it  as  a  liter  of  solution  containing  342  gms.  of  sugar  has 
of  sugar  molecules.  On  the  assumption  that  a  molecule  in  solution  exerts 
an  osmotic  pressure  that  is  exactly  equal  to  the  gas-pressure  exerted  by  a 
gas  molecule  moving  in  the  same  space  and  at  the  same  temperature,  we 
are  justified  in  saying  that  the  osmotic  pressure  of  a  gram-molecular  solu- 
tion of  cane-sugar,  or  of  any  other  substance  that  is  not  an  electrolyte,  is 
equal  to  the  gas-pressure  of  2  gms.  of  H  when  compressed  to  the  volume 
of  1  liter.  This  fact  gives  a  means  of  calculating  the  osmotic  pressure  of 
solutions  in  certain  cases  according  to  the  following  method: 

Calculation  of  the  Osmotic  Pressure  of  Solutions. — To  illustrate  this 
method  we  may  take  a  simple  problem  such  as  the  determination  of  the 
osmotic  pressure  of  a  1  per  eent.  solution  of  cane-sugar.  One  gm.  of  H  at 
atmospheric  pressure  occupies  a  volume  of  11.16  liters;  2  gms.  of  H,  there- 
fore, under  the  same  conditions  will  occupy  a  volume  of  22.32  liters.  A 
gram-molecule  of  H — that  is,  2  gms.  of  H — when  brought  to  the  volume 
of  1  liter  will  exert  a  gas-pressure  equal  to  that  of  22.32  liters  compressed 
to  1  liter — that  is,  a  pressure  of  22.32  atmospheres.  A  gram-molecular  solu- 
tion of  cane-sugar,  since  it  contains  the  same  number  of  molecules  in  a  liter, 
must  therefore  exert  an  osmotic  pressure  equal  to  22.32  atmospheres.  A 
1  per  cent,  solution  of  cane-sugar  contains,  however,  only  10  gms.  of  sugar 
to  a  liter;  hence  the  osmotic  pressure  of  the  sugar  in  such  a  solution  will 
be  ~  of  22.32  atmospheres,  or  0.65  of  an  atmosphere,  which  in  terms  of 

a  column  of  mercury  gives  760  X  0.65  =  494  mms.  This  figure  expresses 
the  osmotic  pressure  of  a  1  per  cent,  solution  of  cane-sugar  when  dialyzed 
against  pure  water  through  a  membrane  impermeable  to  the  sugar  molecules. 
In  such  an  experiment  water  would  pass  to  the  sugar  side  until  the  hydro- 
static pressure  on  this  side  was  increased  by  an  amount  equal  to  the  pres- 
sure of  a  column  of  mercury  494  mms.  high.  Certain  additional  calculations 
that  it  is  necessary  to  make  for  the  temperature  of  the  solution  need  not  be 
specified  in  this  connection.  If,  however,  we  wish  to  apply  this  method 
to  the  calculation  of  the  osmotic  pressure  of  a  given  solution  of  an  electro- 
lyte, it  is  necessary  first  to  ascertain  the  degree  of  dissociation 'of  the  electro- 
lyte into  its  ions,  since,  as  was  said  above,  dissociation  increases  the  num- 
ber of  parts  in  solution  and  to  the  same  extent  increases  osmotic  pressure. 
In  the  body  the  liquids  that  concern  us  contain  a  variety  of  substances  in 
solution,  electrolytes  as  well  as  non-electrolytes.  In  order,  therefore,  to 
calculate  the  osmotic  pressure  of  such  complex  solutions  it  is  necessary  to 
ascertain  the  amount  of  each  substance  present,  and,  in  the  case  of  electro- 
lytes, the  degree  of  dissociation.  Under  experimental  conditions  such  a 
calculation  is  practically  impossible,  and  recourse  must  be  had  to  other 
methods.  One  of  the  simplest  and  most  easily  applied  of  these  methods 
is  the  determination  of  the  freezing  point  of  the  solution. 

Determination  of  Osmotic  Pressure  by  Means  of  the  Freezing  Point. 
— This  method  depends  upon  the  fact  that  the  freezing  point  of  water  is  low- 
ered by  substances  in  solution,  and  it  has  been  discovered  that  the  amount 
of  lowering  is  proportional  to  the  number  of  parts  (molecules  and  ions) 
present  in  the  solution.  Since  the  osmotic  pressure  is  also  proportional  to 
the  number  of  parts  in  solution,  it  is  convenient  to  take  the  lowering  of  the 
freezing  point  of  a  solution  as  an  index  or  measure  of  its  osmotic  pressure. 
In  practice  a  simple  apparatus  (Beckmann's  apparatus)  is  used,  consisting 
essentially  of  a  very  delicate  and  adjustable  differential  thermometer.  By 
means  of  this  instrument  the  freezing  point  of  pure  water  is  first  ascertained 
upon  the  empirical  scale  of  the  thermometer.  The  freezing  point  of  the 
solution  under  examination  is  then  determined,  and  the  number  of  degrees 
or  fractions  of  a  degree  by  which  its  freezing  point  is  lower  than  that  of  pure 
water  is  noted.  The  lowering  of  the  freezing  point  in  degrees  centigrade 
is  expressed  usually  by  the  symbol  A-  For  example,  mammalian  blood- 
serum  gives  A  =  0.56°  C.  A  0.95  per  cent,  solution  of  NaCl  gives  the  same 
A  J  hence  the  two  solutions  exert  the  same  osmotic  pressure,  or,  to  put  it  in 
another  way,  a  0.95  per  cent,  solution  of  NaCl  is  isotonic  or  isosmotic  with 
mammalian  serum.  The  A  of  any  given  solution  may  be  expressed  in  terms 
•of  a  gram-molecular  solution  by  dividing  it  by  the  constant  1.87,  since  a 


1036  APPENDIX. 

gram-molecular  solution  of  a  non-electrolyte  is  known  to  lower  the  freezing 
point  1.87°  C.  Thus,  if  blood-serum  gives  A  =  0.56°  C.,  its  concentration  in 

terms  of  a  gram-molecular  solution  will  be   ^p  or  0.3.     In  other  words, 

blood-serum  has  0.3  of  the  osmotic  pressure  exerted  by  a  gram-molecular 
solution  of  a  non-electrolyte, — that  is,  22.32  X  0.3,  or  6.696  atmospheres. 

Remarks  upon  the  Application  of  the  Foregoing  Facts  in  Physiol- 
ogy.— In  the  body  water  and  substances  in  solution  are  continually  pass- 
ing through  membranes, — for  example,  in  the  production  of  lymph,  in  the 
absorption  of  water  and  digested  foodstuffs  from  the  alimentary  canal,  in 
the  nutritive  exchanges  between  the  tissue  elements  and  the  blood  or  lymph, 
in  the  production  of  the  various  secretions,  and  so  on.  In  these  cases  it  is  a 
matter  of  the  greatest  difficulty  to  give  a  satisfactory  explanation  of  the 
forces  controlling  the  flow  to  and  fro  of  the  water  and  dissolved  substances, 
but  there  can  be  little  doubt  that  in  all  of  them  the  physical  forces  of  nitration 
and  osmotic  pressure  take  an  important  part.  Whatever  can  be  learned, 
therefore,  concerning  these  processes  must  in  the  end  have  an  important 
bearing  upon  the  explanation  of  the  nutritive  exchanges  between  the  blood 
and  tissues.  Some  additional  facts  may  be  mentioned  to  indicate  the  appli- 
cations that  are  made  of  these  processes  in  explaining  physiological  phenomena. 

Osmotic  Pressure  of  Proteins. — The  osmotic  pressure  exerted  by  crys- 
talloids, such  as  the  ordinary  soluble  salts,  is,  as  we  have  seen,  very  con- 
siderable, but  the  ready  diffusibility  of  most  of  these  salts  through  animal 
membranes  limits  very  materially  their  influence  upon  the  flow  of  water  in 
the  body.  Thus,  if  we  should  inject  a  strong  solution  of  common  salt  directly 
into  the  blood-vessels,  the  first  effect  would  be  the  setting  up  of  an  osmotic 
stream  from  the  tissues  to  the  blood  and  the  production  of  a  condition  of 
hydremic  plethora  within  the  blood-vessels.  The  salt,  however,  would  soon 
diffuse  out  into  the  tissues,  and  to  the  degree  that  this  occurred  its  effect  in 
diluting  the  blood  would  tend  to  diminish  because  the  part  of  the  salt  that 
got  into  the  extravascular  lymph  spaces  would  now  exert  an  osmotic  press- 
ure in  the  opposite  direction,  drawing  water  from  the  blood.  This  fact, 
together  with  the  further  fact  that  an  excess  of  salts  in  the  body  is  soon  re- 
moved by  the  excretory  organs,  gives  to  such  substances  a  smaller  influence 
in  directing  the  water  stream  than  would  at  first  be  supposed  when  the  inten- 
sity of  their  osmotic  action  is  considered.  In  addition  to  the  crystalloids  the 
liquids  of  our  bodies  contain  also  a  certain  amount  of  protein,  the  blood, 
especially,  containing  over  6  per  cent,  of  this  substance.  It  has  been  gen- 
erally assumed  that  proteins  in  solution  exert  little  or  no  osmotic  pressure, 
but  Starling  *  and  others  have  claimed,  on  the  contrary,  that  they  exert  a 
distinct,  although  small,  osmotic  pressure,  and  it  is  possible  that  this  fact 
is  of  special  importance  in  absorption,  because  the  proteins  do  not  diffuse 
or  diffuse  with  great  difficulty,  and  their  effect  remains,  therefore,  so  to 
speak,  as  a  permanent  factor.  According  to  Starling,  the  osmotic  pressure 
exerted  by  the  proteins  of  serum  is  equal  to  about  30  mms.  of  mercury.  That 
the  osmotic  pressure  of  the  serum  proteins  is  so  small  is  not  surprising  if  we 
remember  the  very  high  "molecular  weight  of  this  substance.  In  serum  the 
proteins  are  present  in  a  concentration  of  about  7  per  cent.,  but  owing  to 
their  large  molecular  weight  comparatively  few  protein  molecules  are  present 
in  a  solution  of  this  concentration  ;  and,  assuming  that  the  dissolved  protein 
follows  the  laws  discovered  for  crystalloids,  its  osmotic  pressure  would  depend 
upon  the  number  of  molecules  in  solution.  By  means  of  this  weak  but  con- 
stant osmotic  pressure  of  the  indiffusible  protein  it  is  possible  to  explain 
theoretically  the  fact  that  an  isotonic  or  even  a  hypertonic  solution  of  diffusi- 
ble crystalloid  may  be  completely  absorbed  by  the  blood  from  the  peritoneal 
cavity. 

Isotonic,  Hypertonic,  and  Hypotonic  Solutions. — In  physiology  the 
osmotic  pressures  exerted  by  various  solutions  are  compared  usually  with 
that  of  the  blood-serum.  In  this  sense  an  isotonic  or  isosmotic  solution  is 
one  having  an  osmotic  pressure  equal  to  that  of  serum,  a  hypertonic  or  hy- 
perosmotic  solution  is  one  whose  osmotic  pressure  exceeds  that  of  serum, 

*  "Journal  of  Physiology,"  24,  317,  1899. 


PROTEINS    AND    THEIR    CLASSIFICATION.  1037 

and  a  hypotonic  or  hyposmotic  solution  is  one  whose  osmotic  pressure  is 
less  than  that  of  serum. 

Diffusion,  or  Dialysis,  of  Soluble  Constituents. — If  two  liquids  of 
unequal  concentration  in  a  given  constituent  are  separated  by  a  membrane 
entirely  permeable  to  the  dissolved  molecules  of  the  substance,  a  greater 
number  of  these  molecules  will  pass  over  from  the  mo^e  concentrated  to  the 
less  concentrated  side,  and  in  time  the  composition  will  be  the  same  on  the 
two  sides  of  the  membrane.  Diffusion  of  soluble  constituents  continually 
takes  place,  therefore,  from  the  points  of  greater  concentration  to  those  of 
less,  and  this  may  happen  quite  independently  of  the  direction  of  the  osmotic 
stream  of  water.  If,  for  instance,  a  0.9  per  cent,  solution  of  sodium  chlorid 
is  injected  into  the  peritoneal  cavity,  it  will  enter  into  diffusion  relations 
with  the  blood  in  the  blood-vessels;  its  concentration  in  sodium  chlorid 
being  greater  than  that  of  the  blood,  the  excess  will  tend  to  pass  into  the 
blood,  while  sodium  carbonate,  urea,  sugar,  and  other  soluble  crystalloidal 
substances  will  pass  from  the  blood  into  the  salt  solution  in  the  peritoneal 
cavity.  Through  the  action  of  this  process  of  diffusion  we  can  understand 
how  certain  constituents  of  the  blood  may  pass  to  the  tissues  of  various  glands 
in  amounts  greater  than  can  be  explained  if  we  supposed  that  the  lymph 
of  these  tissues  is  derived  solely  by  nitration  from  the  blood-plasma.  An- 
other important  conception  in  this  connection  is  the  possibility  that  the 
capillary  walls  may  be  permeable  in  different  degrees  to  the  various  soluble 
constituents  of  the  blood,  and  furthermore  the  possibility  that  the  permea- 
bility of  the  capillary  walls  may  vary  in  different  organs.  With  regard  to 
the  first  possibility  it  has  been  shown  that  the  blood  capillaries  are  more 
permeable  to  the  urea  molecules  than  to  sugar  or  Nad.  With  the  aid  of 
these  facts  it  is  possible  to  explain  in  large  measure  the  transportation  of 
material  from  the  blood  to  the  tissues,  and  vice  versa.  For  example,  to  follow 
a  line  of  reasoning  used  by  Roth,  we  may  suppose  that  the  functional  activity 
of  the  tissue  elements  is  attended  by  a  consumption  of  material  which  in 
turn  is  made  good  by  the  dissolved  molecules  in  the  tissue  lymph.  The 
concentration  of  the  latter  is  thereby  lowered,  and  in  consequence  a  diffu- 
sion stream  of  these  substances  is  set  up  with  the  more  concentrated  blood. 
In  this  way,  by  diffusion,  a  constant  supply  of  dissolved  material  is  kept 
in  motion  from  the  blood  to  the  tissue  elements.  On  the  other  hand,  the 
functional  activity  of  the  tissue  elements  is  accompanied  by  a  breaking  down 
of  the  complex  protein  molecule,  with  the  formation  of  simpler,  more  stable 
molecules  of  crystalloid  character,  such  as  the  sulphates,  phosphates,  and 
urea  or  some  precursor  of  urea.  As  these  bodies  pass  into  the  tissue  lymph 
they  tend  to  increase  its  concentration,  and  thus  by  the  greater  osmotic 
pressure  developed  they  serve-  to  attract  water  from  the  blood  to  the  lymph, 
forming  one  efficient  factor  in  the  production  of  lymph.  On  the  other  hand, 
as  these  substances  'accumulate  in  the  lymph  to  a  concentration  greater  than 
that  possessed  by  the  same  substances  in  the  blood,  they  will  diffuse  toward 
the  blood.  By  this  means  the  waste  products  of  activity  are  drawn  off  to 
the  blood,  from  which,  in  turn,  they  are  removed  by  the  action  of  the  excretory 
organs. 

Diffusion  of  Proteins. — This  simple  explanation  on  purely  physical 
grounds  of  the  flow  of  material  between  the  blood  and  the  tissues  can  only 
be  applied,  however,  at  present  to  the  diffusible  crystalloids,  such  as  the 
salts,  urea,  and  sugar.  The  proteins  of  the  blood,  which  are  supposed  to 
be  so  important  for  the  nutrition  of  the  tissues,  are  practically  indiffusible 
through  animal  membranes,  so  far  as  we  know.  It  is  difficult  to  explain  their 
passage  from  the  blood  through  the  capillary  walls  into  the  lymph.  Pro- 
visionally it  may  be  assumed  that  this  passage  is  due  to  filtration.  The  blood- 
plasma  in  the  capillaries  is  under  a  slightly  higher  pressure  than  the  lymph  of 
the  tissues,  and  this  higher  pressure  tends  to  squeeze  the  blood  constituents, 
including  the  protein,  through  the  capillary  walls.  So  far  as  the  protein  nutri- 
tion of  the  tissues  is  concerned,  the  difficulty  in  regard  to  the  indiffusibility  of  the 
proteins  is  met  by  the  modern  conception  that  the  digested  protein  of  the  food 
circulates  in  the  blood  as  amino-acids,  and  is  supplied  to  the  tissues  in  this 
form.  The  amino-acids  have  much  simpler  molecules  and  may  pass  through 
the  capillary  walls  by  diffusion. 


INDEX. 


ABDERHALDEN  test,  754 
Abdominal  respiration,  650 

type  of  respiration,  654 
Absolute  power  of  muscle,  39 
Absorption  coefficient,  679 

in  large  intestine,  812 

in  small  intestine,  806 

in  stomach,  791 

of  carbohydrates,  808 

of  fats,  809 

of  proteins,  811 

spectra  of  hemoglobin,  432 
Acapnia,  708,  714 
Accelerator  center  for  heart,  599 

nerves,  effect  of,  on  heart-rate,  601 
of  heart,  595 
reflex  stimulation  of,  597 
Accessory  thyroids,  874 
Accommodation  in  eye,  limits  of,  316 
mechanism  of,  313 

reflex,  326 
Acetone  bodies,  925 
Achromatic  series  of  visual  sensations, 
349 

vision,  357 
Achroodextrin,  772 
Acid,  aceto-acetic,  925 

albumin  in  gastric  digestion,  786 

amino-acetic,  799,  1025 

aminocaproic,  800,  1025 

aminoglutaric,  1025 

aminopropionic,  799,  1025 

aminosuccinic,  800,  1025 

aminothiopropionic,  1025 

aminovalerianic,  800,  1025 

aspartic,  800,  1025 

cholic,  822 

conjugated  sulphuric,  814,  861 

diaminocaproic,  800,  1025 

glutaminic,  8*00,  1025 

glycocholic,  822 

glycuronic,  917 

guanidinaminovalerianic,  1025 

hippuric,  860 

imidazolpropionic,  801, 1025 

indolpropionic,  801, 1025 

isobutylpropionic,  800 

lactic,  63 

oxyaminopropionic,  1025 

oxybutyric,  925 

oxyphenylaminopropionic,  1025 


Acid,  oxypropionic,  799 
oxyproteic,  853 

oxypyrollidin-carboxylic,  799,  1025 
phenylaminopropionic,  800,  1025 
pyrrolidin-carboxylic,  801,  1025 
taurocholic,  821 
thiopropionic,  799 
Acidosis,  419,  921 
Acromegaly,  891 
Action  current,  diphasic,  103 
in  heart,  545 
in  muscle,  102 
in  nerve,  102 
in  retina,  337 
monophasic,  103 
relation  to  contraction  wave,  105 

to  nerve  impulse,  105 
Activation  of  lipase,  804 

of  trypsin,  797 
Activators,  755 
Adamkiewicz's  reaction  for  proteins, 

1029 

Addison's  disease,  881 
Adenase,  756,  858 
Adenin,  64,  857 
Adenosin,  858 
Adrenal  bodies,  functions  of,  886 

secretory  nerves  of,  886 
Adrenalin,  879,  883 
Adrenin,  883 
Aerial  perspective,  376 
Aerotonometer,  680 
Afferent  fibers  in  cranial  nerves,  83 
position   of,    in    posterior   roots, 

82 

vasodilatation  due  to,  623 
nerve-fibers,  79 
After-images  in  eye,  352 
Agnosia,  205,  222 
Agraphia,  221 

Air,   effect  of  variations  in,  on  res- 
pirations, 711 
Alanin,  799,  912,  1025 
Albumin,  properties  of,  1029.  See  also 

Protein. 

Albuminoids,  nutritive  value  of,  909 
Albumon,  453 
Alcohol  as  food,  936 

effect  of,  on  gastric  absorption,  792 

on  respiratory  quotient,  716 
physiological  action  of,  937 

1039 


1040 


INDEX. 


Alcohol,  use  of,  in  diabetes,  940 

Alexia,  221 

Alexins,  426 

Alimentary  canal,  movements  of,  719 

glycosuria,  808 

principles  of  food,  744 
All  or  none  law,  29 
Altitude,  effect  of,  on  red  corpuscles, 

440 

Amboceptors,  426 
Ametropia,  319 
Amines,  815 

Ammo-acetic  acid,  799,  1025 
Amino-acids  as  part  of  protein  mole- 
cule, 799, 1025 

Aminocaproic  acid,  800, 1025 
Aminoglutaric  acid,  1025 
Aminopropionic  acid,  799,  1025 
Aminopurins,  857 
Aminosuccinic  acid,  800,  1025 
Aminovalerianic  acid,  800,  1025 
Ammonia  nitrogen  in  urine,  852 

salts,  relation  of,  to  urea,  854 
Ammonium   carbamate  as  precursor 
of  urea,  854 

carbonate  as  precursor  of  urea,  854 
Amylase,  802 
Amylolytic  enzyme,  753 
Anacrotic  pulse,  530 
Anaglyph,  379 
Anaphylaxis,  754 
Anelectrotonic  currents,  107 
Anelectrotonus,  87 
Angstrom  unit,  336 
Anisotropous  substance  in  muscle,  20 
Anode  as  stimulus  to  muscle,  87 
to  nerve,  87 

physical,  93 

physiological,  93 

Anomalous  trichromatic  vision,  354 
Anoxemia,  712 
Anterior  commissure,  187,  217 

roots  of  spinal  nerves,  82 
Antidromic    impulse    in    vasodilator 

nerve-fibers,  82 
Antigen,  425 
Antilytic  secretion,  769 
Antiparalytic  secretion,  769 
Antiprothrombin,  464 
Antithrombin,  462,  464 
Antrum  pylori  of  stomach,  725 
Anus  praeternaturalis,  812 
Apex-beat  of  heart,  549 
Aphasia,  motor,  219 

sensory,  221 
Aphemia,  219,  221 
Apnea,  706 
Apraxia,  221 
Arginase,  856 

Arginin,  800,  856,  912,  1006,  1031 
Argyll-Robertson  pupil,  327 
Arterial  pressure,     See  Circulation. 


Artificial  muscle  of  Engelmann,  71,  72 
respiration,  659,  668 
stimuli  of  nerve-fibers,  84 
Ascending  paths  in  spinal  cord,  169 
Aspartic  acid,  799,  912,  1025 
Asphyxia,  707 

effect  of,  on  heart-rate,  603 
Aspiratory  action  of  thorax,  665 
Association  areas  in  brain,  223,  225 
system  of  fibers  in  cerebrum,  185 
Astereognosis,  204 
Astigmatism,  320 
Atropin,  action  of,  on  heart,  593 
on  iris,  328 

on  salivary  secretion,  768 
on  sweat  secretion,  870 
Auditory  center  in  cortex,  212 
nerve~  course  of,  in  brain,  213 

effect  of  section  of,  408 
sensations.    See  Ear. 
striae,  215 

Auricle.    See  Heart. 
Auriculo ventricular  bundle  of  heart, 

540,  580 

effect  of  compressing,  582 
node,  542 
Auscultation,  556 
Autacoid  substances,  874 
Autolysis,  976 
Autolytic  enzymes,  756 
Automaticity  of  heart-beat,  573 
Autonomic,  bulbar,  739 
fibers  from  brain,  255 
from  sacral  cord,  256 
from  spinal  cord,  253 
nerve-fibers,  normal  stimulation  of, 

257 
nervous    system,    general    relation 

of,  251 
Autonomies,  sacral,  739,  740 

thoracic,  739,  740 
Axial  stream  in  arteries  and  veins, 

484 
Axon  reflexes,  151 


BACTERIAL  action  in  intestines,  813 

Balance  experiments  in  nutrition,  901 

Balloon  ascensions,  effect  of,  714 

Barany  tests,  408 

Barometric  pressures,  effect  of,  713 

Bartholin,  duct  of,  758 

Basal  metabolism,  966 

Basilar  membrane,  function  of,  399 

Bathmotropic   nerve-fibers   to   heart, 

589 

Bechterew's  nucleus,  214,  235 
Bell-Magendie  law,  82 
Beri-beri,  913 
Betz  cells,  179 
Bilateral     representation     in     motor 

areas,  199 


INDEX. 


1041 


Bile,  composition  of,  818 
curve  of  secretion  of,  826 
effect  of  occluding  bile-ducts,  827 
ejection  of,  into  duodenum,  826 
functions  of,  summary,  828 
quantity  of,  819 
secretion  of,  824 
Bile-acids,  composition  of,  821 
Bile-duct,  sphincter  of,  827 
Bile-pigments,  438,  820 
Bile-salts,  importance  of,  in  fat  diges- 
tion, 810,  828 
Bilirubin,  820 
Biliverdin,  820 

Binocular  perspective,  378,  380 
vision,  368 

horopter  in,  375 

struggle  of  visual  fields  in,  375 

value  of,  in  judgments  of  distance, 

381 

of  size,  381 

Biologic  value  of  protein,  904 
Biological  reaction,  425 
Births,  ratio  of  male  and  female,  1015 
Biuret  reaction  for  proteins,  1028 
Bladder,  gall-,  movements  of,  826 
urinary,  movements  of,  864 

sphincter  of,  864 
Blind  spot  in  eye,  337 
Blood,  blood-plates  of,  physiologv  of, 

445 

circulation  of.     See  Circulation. 
coagulation  of,  453 
condition  of  carbon  dioxid  in,  684 

of  nitrogen  in,  681 
curve  of  dissociation  of  oxyhemo- 

globin,  683 
defibrinated,  416 
gases  of,  674 

general  properties  of,  415 
hemoglobin  of,  421 
amount,  427 
nature,  427 

hemolysis  of  reck  corpuscles,  422 
histological  structure  of,  415 
leukocytes  of,  443 
meionectic,  684 
mesectic,  684 
nucleoprotein  in,  453 
osmotic  pressure  of,  423 
oxygen-pressure  of,  690 
peptonised,  464 
pleonectic,  684 
proteins  of,  448,  450 
reaction  of,  416 
red  corpuscles  of,  421 
fate  of,  438 
origin  of,  438 
regeneration  of,  after  hemorrhage, 

470 

specific  gravity  of,  419 
total  quantity  of,  469 


Blood,  transfusion  of,  472 
Blood-plasma,  composition  of,  448 
Blood-plates,  properties  of,  445 
Blood-pressure,  491 

diastolic,  495 

effect  of  menstruation  upon,  987 

in  brain,  635,  636 

in  capillaries,  501 

in  man,  502,  508 

mean,  495 

relation  of,  to  heart-rate,  601 

respiratory  waves  of,  666 

systolic,  495 

Traube-Hering  waves  of,  620 

venous  and  capillary,  509 
Blood-serum,  416,  449 
Body  equilibrium  in  nutrition,  901 

sense  area,  203 

temperature  in  man,  958 
Bowman's   theory   of   urinary   secre- 
tion, 841 
Brachium  conjunctivum,  235 

pontis,  237 
Brain,  association  areas  of,  223 

auditory  center  in,  212 

center  for  olfaction,  216 
for  taste,  218 

centers  affected  in  aphasia,  219,  223 

development  of  cortical  areas,  226 

effect  of  variations  in  arterial  pres- 
sure upon,  634 

histological   differentiation   of   cor- 
tex of,  229 

intracranial  pressure  in,  632 

localization  of  function  in,  192 

motor  areas  of,  196 

regulation  of  circulation  in,  628 

sensory  areas  of,  202 

vascular  supply  of,  628 
Brightness  in  visual  sensations,  347 
Bronchi,  capacity  of,  658 

constrictor  and  dilator  fibers  of,  709 
Bulbar  autonomic,  739 
Bulbospiral  fibers  of  heart,  539 


CAFFEIN,  935 

Caisson  disease,  712 

Calcarine  fissure,  relation  of,  to  vision, 

210 
Calcium, .  amount  of,  in  cataract,  934 

in  clotting  of  blood,  459,  460 

salts,  effect  of,  in  curdling  of  milk,  788 

on  heart,  574 
nutriitve  value  of,  932 
secretion  of,  in  milk,  477 
Calorie,  definition  of,  960 
Calorimeters,  varieties  of,  961 
Calorimetric  equivalent,  962 

measurements,  965 
Calorimetry,  indirect,  963 

principles  of,  960  j 


1042 


INDEX. 


Cannula,  washout,  493 
Capillary  blood-pressure,  501 

electrometer,  construction  of,  98 
Carbohemoglobin,  430 
Carbohydrates,  absorption  of,  808 
as  glycogen  formers,  830 
as  source  of  body  fat,  928 
fermentation  of,  in  intestine,  813 
general  functions  of,  922 
metabolism  of,  in  body,  916 
of  muscle,  62 

regulation  of  suppty  of,  918 
supply  of,  in  body,  915 
Carbon  dioxid,  action  on  respiratory 

center,  703 

condition  of,  in  blood,  684 
effect  of,  in  inspired  air,  703,  712 
on    dissociation    of    oxyhemo- 

globin,  682 

on  respiratory  movements,  703 
excretion  of,  through  skin,  872 
in  balance  experiments,  901 
in  saliva,  761 

production  of,  in  muscle,  65 
tension  of,  in  alveolar  air,  686 
in  arterial  blood,  688 
in  tissues,  688 
in  venous  blood,  688 
equilibrium,  901 
monoxid  hemoglobin,  430 
Cardiac  cycle,  559 

glands  of  stomach,  774 
muscle,  properties  of,  57,  577 
nerves.    See  Heart. 
sphincter,  724 
Cardiogram,  550 
Cardio-inhibitory  center,  590 
Carnin,  64 
Carnosin,  63 
Casein,  788,  1002 
Catalase,  749,  757,  977 
Catalysis,  749 

Catelectrotonic  currents,  107 
Catelectrotonus,  87 
Cathode  as  stimulus,  87 

physical  and  physiological,  93 
Centers  in  cerebrum.    See  Cerebrum. 
Central  field  of  vision,  342 

pulse,  529 
Centrosome,  990 
Cephalin,  464 

Cephalin-protein  compound,  462 
Cerebellum,   ending  of  spinal  tracts 

in,  V72,  236 

experimental  work  upon,  239 
general  functions  of,  242 
localization  of  function  in,  243 
paths  connecting  with  other  parts 

of  brain,  235 

physical  functions  of,  243 
structure  of,  233 
Cerebrin,  79 


Cerebrogalactosides,  79 
Cerebrosides,  79 
Cerebrospinal  liquid,  630 

origin  of,  632 
Cerebrum,  association  areas  of,  223. 

225 

center  for  hearing,  212 
for  olf action,  216 
for  vision,  207 

centers  affected  in  aphasia,  219 
commissural   system    of   fibers   in, 

186 
development  of  cortical  areas  in, 

226 

general  physiology  of,  183 
histological  differentiation  of  cortex, 

229 

history  of  cortex,  184 
localization  of  function  in,  192 
motor  areas  of,  196 
projection  system  of  fibers  in,  185 
results  of  ablation  of,  190 
sensory  areas  of,  202 
system  of  fibers  in,  185 
vasomotor  supply  of,  636 
Cerumen,  871 

Chemical  heat  regulations,  971 
secretion,  gastric,  783 

pancreatic,  797 
Chemotaxis,  126,  992 
Cheyne-Stokes  respiration,  716,  717 
Cholesterin,  78,  817,  823,  871 
Cholic  acid,  822 
Cholin,  78 

Chorda  tympani  nerve,  294,  759,  761 
Chromaffm  system,  882,  883 

tissue,  883 

Chromaphil  system,  882,  883 
Chromatic  aberration  in  eye,  319 

visual  sensations,  350 
Chromatolysis,  129 
Chromophile  substance  in  nerve-cells, 

134 

Chromoproteins,  1031 
Chromosomes,  990,  1011 
Chronotropic    nerve-fibers    to    heart, 

589 

Chyle  fat,  810 
Chymosin,  788 

Ciliary  muscle,  action  of,  in  accom- 
modation, 314 
nerves  to,  324 
Ciliated  epithelium,  58 
Circulating  proteins,  905 
Circulation,  accessory  factors  in,  520 
as  seen  under  microscope,  484 
curve  showing  pressures  in,  496,  499, 

501 
data  concerning  mean  pressures  in, 

500 

pressures  in  (man),  508 
diastole  and  systole  of  heart,  537 


INDEX. 


1043 


Circulation,  effect  of  adrenal  extracts 

upon,  881,  882 
of  heart-beat  and  size  of  arteries  j 

upon,  489 

explanation  of  side  pressure  in,  513 
of  velocity  changes  in,  489 

pressure  in,  514 
factors    of    normal    pressure    and 

velocity  in,  516 
form  of  pulse  wave,  526 
general  curve  of  velocities  in.  489 
statement  of  pressure  relations, 

491 

hydrostatic  effects  upon,  518 
importance  of  elasticity  of  arteries, 

515 

in  brain,  628 
in  kidneys,  847 

means   of  determining  blood-pres- 
sure in,  491,  503 
velocities  in,  487 
pressure  in  coronary  system,  593 

in  pulmonary  system,  521 
pulse  pressures  in,  495 
regulation  of  blood  supply,  624 
respiratory   waves   of  pressure   in, 

666 

systole  and  diastole  of  heart,  537 
systolic,  diastolic,  and  mean  pres- 
sures in,  495 
velocities  in,  487 
time  required  for  complete,  490 
Traube-Hering   waves   of   pressure 

in,  620 

velocity  in  capillaries,  487 
in  coronary  system,  561,  562 
in  man,  487 

in  pulmonary  system,  521 
of  pulse  wave,  524 
Clarke's  column,  163 
Claudication,  intermittent,  34 
Clotting.     See  Coagulation. 
Coagulation,  blood,  453 
intravascular,  465 
means  of  hastening  and  retarding, 

466 

theories  of,  456 

Cocain,  action  of,  on  iris,  328 
Cochlea,  functions  of,  398 

sensory  epithelium  of,  392 
Coefficient,  absorption,  679 

temperature,  114 
Coferment,  755 
Cold  spots  on  skin,  280 
Color  blindness,  354 
contrast,  353 
fusion,  350 
saturation,  350 
sense  of  retina,  357 
vision,  theories  of,  360 
Combustion  equivalents  of  foods,  948 
Comma  tract  of  Schultze,  180 


Commissural  system  of  fibers   (cere- 
brum), 186 

Common  sensations,  272 
Compensatory   pause   in    heart-beat, 

580 

Complemental  air,  658 
Complementary  colors,  351 
Compound  muscular  contractions,  42 
Condiments,  747,  935 
Conditioned  reflexes,  190 
Conduction  as  physiological  property, 

75 

direction  of,  in  nerve-fibers,  113 
Conjugate  foci,  307 
Conjugated  sulphates,  861 
Contraction,  17,  32.     See  also  Muscle. 
Contralateral  conduction  in  cord,  176 
Convoluted  tubules  of  kidney,  839,  844 
Core-model  of  nerve,  108 
Coronary  arteries,  effect  of  occlusion 

of,  565 

vasomotor  supply  of,  626 
Corpora  quadrigemina,  relation  of,  to 

visual  apparatus,  208,  211 
striata,  functions  of,  231 
Corpus  callosum,  structure  and  func- 
tion, 230 
luteum,  982 
trapezoideum,  215 
Corresponding  points  of  retina,  376 
Cortex  of   cerebrum,    general   physi- 
ology of,  186 
histology  of,  183,  229 
Corti,  rods  of,  392 
Cortical   tissue   function   significance 

of,  887 

Costal  respiration,  654 
Cowper's  glands,  1005 
Cranial  nerves,  afferent  fibers  in,  83 
efferent  fibers  of,  83 
nuclei  of  origin  of,  245 
Cranioscopy,  192 
Creatin.  63,  859 
Creatinin,  63,  859 
Cresol-sulphuric  acid,  814,  862 
Cretinism,  875,  878 
Crystalline  lens,  calcium  of,  in  cata- 
ract, 934 
Curve,  contraction,  of  arterial  pulse, 

527,  530 

of  artificial  muscle,  73 
of  plain  muscle,  57 
of  skeletal  muscle,  26 
dissociation  of  oxyhemoglobin,  683 
extensibility  and  elasticity  of  mus- 
cle, 20 

gastric  secretion,  783 
intensity  of  sleep,  260 
pancreatic  secretion,  795 
pressures  in  vascular  system,  496, 

499,  501 
relations  of  heart  sounds,  557,  558 


1044 


INDEX. 


Curve,  respiratory  movements,  656 

secretion  of  bile,  826 

systolic,  diastolic,  and  mean  blood- 
pressures,  495 

velocity  of  blood-flow,  489 

venous  pulse,  533 

visual  acuity  of  retina,  345 

work  of  muscle,  41 
Cycloplegia,  329 
Cystein,  799,  823 
Cytozym,  463 


DEAD  space  of  lungs,  659 

Deamidizing  enzymes,  754 

Death  rigor,  chemical  changes  during, 

68 
in  muscle,  52 

theories  of,  1019 
Deep  reflexes,  160 

sensibility,  278,  288,  289 
Defecation,  739 

Degeneration  in  nerve-fibers,  124 
Deglutition,  719 

nervous  control  of,  722 
Deiter's  cells  in  cochlea,  392 

nucleus,  214,  235 
Demarcation    current,     muscle     and 

nerve,  95 

Demilunes  of  salivary  glands,  758 
Depressor  nerve-fibers,  615 

of  heart,  618 
Derived  proteins,  1032 
Descending  paths,  spinal   cord,  178, 

180 

Deuteranopia,  355 
Deutero-albumoses,  786 
De  Vries'  theory  of  mutation,  1012 
Dextrose,  916,  917 
Diabetes  mellitus,  898,  919 

pancreatic,  898,  919 

phloridzin,  921 

use  of  alcohol  in,  940 
Dialysis,  definition  of,  1037 
Diaphragm,  action  of,  650 
Diaphragmatic  respiration,  650 
Diaschisis,  195 
Diastase,  753 

discovery  of,  748 
Diastasis  of  heart,  555 
Diastole,  duration  of,  in  heart,  560 
Diastolic  arterial  pressure,  495 

method  of  determining,  in  ani- 
mals, 497 
in  man,  503 

Dicrotic  pulse  wave,  528 
Diet,  accessory  articles  of,  747,  935 

average  daily,  950-952 

effect  of  reduction  of  salts  in,  932 
Dietetics,  general  principles  of,  950 
Diffusion  circles  on  retina,  313 

definition  of,  1032 


Digestion  in  large  intestine,  812 

in  small  intestine,  793 

in  stomach,  790 
Diopter,  definition  of,  317 
Dioptrics  of  eye,  306 
Diplopia,  370,  373 
Direct  field  of  vision,  eye,  342 
Discord,  physiological  explanation  of 

402 

Dissociation  of  oxyhemoglobin,  683 
Diuretics,  action  of,  846 
Dominant  characteristics  in  heredity . 

1013 

Dromograph,  486 

Dromotropic  nerve-fibers  to  heart,  589 
Dualistic    theory    (blood-corpuscles), 

443 
Duct  of  Bartholin,  758 

of  Rivinus,  758 

of  Stenson,  758 

of  Wharton,  758 

of  Wirsung,  793 
Dyspnea,  653,  706 
Dyspraxia,  231 


EAR,    effect   of   section   of    auditory 

nerves,  408 
of    stimulation    of    semicircular 

canals,  409 

Eustachian  tube  of,  493 
Flourens'     experiments     on     semi- 
circular canals,  405 
functions  in  analyzing  sound  waves, 

398 

of  cochlea,  398 
of  ear-bones,  387 
of  sacculus,  412 
of  utriculus,  412 
intrinsic  muscles  of,  390 
limits  of  hearing,  402 
position  of  bones  in,  387 
projection   of  auditory   sensations, 

391 

semicircular  canals  of,  404 
sensations  of  discord,  402 

of  harmony,  402 

sensory  epithelium  in  cochlea,  392 
structure  of,  393,  399 

bones  of,  387 
theories  of  functions  of  semicircular 

canals  of,  409 

tympanic  membrane  of,  386 
Eck  fistula.  854 
Efferent  nerve-fibers,  79 

occurrence  in  anterior  roots,  81 

in  cranial  nerves,  83 
Ejaculation  of  spermatic  liquid,  1008 
Elasticity  and  extensibility  of  muscle, 

20 

Electrical  changes  in  heart,  545,  698 
in  muscle  and  nerve,  95 


INDEX. 


1045 


Electrical   changes   with    respiratory 

movements,  698 
Electrocardiograms,  545 
Electrodes,  non-polarizable,  100 

stimulating,  86 
Electrolytes,    effect    of,    on    osmotic 

pressure,  1034 
Electrotonic  currents,  107 
Electrotonus,  87 

Eleventh  cranial  nerve,  nucleus  of,  250 
Embryo,  nutrition  of,  995 
Endocrin  system,  873 
Endogenous  fibers  of  spinal  cord,  170 
Energy  of  muscular  contraction,  37 
Enterokinase,  797,  799,  805 
Entoptic  phenomena,  366 
Enzymes,  adenase,  756,  857 

amylase,  802 

arginase,  856 

chemistry  of,  757 

classification  of,  752 

deaminizing,  754 

definition  of,  752 

endoenzymes,  752 

enterokinase,  797,  805 

erepsin,  802,  806 

exoenzymes,  752 

general  properties  of,  754 

glycolytic,  756 

guanase,  756,  858 

historical  account  of,  747 

intracellular,  975 

inverting,  806 

lipase,  803 

nuclease,  756 

of  muscle,  64 

oxidases,  754,  976 

pepsin,  784 

peroxidases,  976 

protective,  753 

ptyalin,  771 

rennin,  788 

reversible  reactions  of,  750 

specificity  of,  751 

trypsin,  798 
Epi  critic  sensations,  279 

sensibility,  278 
Epigenesis,*1006 
Epinephrin,  884,  886,  887 

increased,  effect  on  heart-beat,  604 

physiological  action  of,  883 
Erection,  physiology  of,  1007 
Erepsin,  806 
Ergograph,  48 
Erythroblasts,  440 

Erythrocytes.        See    Red    blood-cor- 
puscles. 

Erythrodextrin,  772 
Eserin,  action  of,  on  iris,  328 
Ethereal  sulphates,  862 
Eupnea,  653 
Eustachian  tube,  391 


Evolution,  hypothesis  of,  in  heredity, 
1010 

Exogenous  fibers  in  spinal  cord,  170 

Exophthalmic  goiter,  878,  879 

Expiration.    See  also  Respiration. 
definition  of,  649 
expiratory  center,  700 
muscles  of,  652 

Expired  air,  composition  of,  669 
injurious  effects  of,  670 

Extensibility  of  muscle,  20 

Extensor  thrust  reflex,  158 

Eye,   abnormalities  in  refraction  of. 

319 

accommodation  in,  313 
action  of  drugs  upon,  328 
acuity  of  vision  in,  343 
after-images  in,  352 
as  optical  instrument,  306 
binocular  field  of  vision,  372 

perspective,  378 
chromatic  aberration  in,  319 
color  blindness  of,  354 
contrasts  in,  353 
vision  in,  349 
complementary  colors,  351 
corresponding  points  in,  372 
dark  adapted,  338,  346 
diffusion  circles  in,  313 
diplopia  in,  370,  373 
direct  field  of  vision  in,  342 
entoptic  phenomena  in,  366 
far  point  of  distinct  vision,  316 
function  of  cones,  358 

of  rods,  358 

fundamental  color  sensations,  351 
horopter,  375 

indirect  field  of  vision  in,  342 
inversion  of  image  in,  311 
light  adapted,  338,  347 

reflex  in,  326 
movements  of,  368 
muscular  insufficiency,  370 
nature  of  visual  stimuli,  338 
near  point  of  distinct  vision,  316 
nodal  point  of,  310 
ophthalmoscopic    examination    of. 

331 
optical  defects  of,  319 

delusions.  382 
physics  of  formation  of  image  in, 

309 

qualities  of  visual  sensations,  349 
reduced  schematic  (Listing),  310 
refractive  power  of.  317 
size  of  retinal  images,  312 
spherical  aberration  in,  319 
steroscopic  vision,  378 
struggle  of  visual  fields,  375 
suppression  of  visual  images,  375 
theories  of  color  vision,  360 
threshold  stimulus  of,  345 


1046 


INDEX. 


Eye,  visual  field  of,  340 

judgments,  376 

purple  of,  338 
Eye-muscles,  action  of,  368 


FACIAL  nerve,  dilator  fibers  in,  620 

nucleus  of,  249 

Far  point  of  distinct  vision,  316 
Fat,  absorption  of,  809 

as  glycogen  former,  832 

digestion  of,  803 
in  stomach,  792 

excessive  formation  of,  in  obesity, 
928 

in  bile,  824 

metabolism  of,  in  body,  924 

mode  of  oxidation  of,  in  body,  925 

nutritive  value  of,  924 

of  chyle,  810 

origin  of,  from  carbohydrates,  927 

in  body,  927 
Fatigue  in  nerve-fibers,  116 

muscular,  50 

of  olfactory  organs,  303 

theories  of,  69 

toxin,  70,  672 
Feces,  composition  of,  816 
Fermentation  in  intestine,  813 

of  carbohydrates  in  small  intestine, 

809 

Ferments,  historical  account  of,  747 
Fertilization  of  ovum,  992 
Fertilizin,  994 

Fibrillary  contractions  of  heart,  566 
Fibrin  ferment,  preparation  of,  456 
relations  to  blood-clot,  453,  454 
Fibrinogen,  451 

preparation  of,  456 
Fictitious  meal  (Pawlow),  780 
Fifth  cranial  nerve,  247 
Fillet,  lateral,  215 

median,  204 
Fistula,  Ecks',  854 

gall-bladder,  819 

stomach,  776 

Thiry-Vella,  804 
Flavors,  746 

dietary,  importance  of,  935 
Flechsig's  myelinization  method,  165 
Fluorid   solution,  effect   on   clotting, 

468 
Food  accessories,  746 

composition  of,  746 

definition  of,  746 

potential  energy  of,  946 
Foodstuffs,  definition  of,  746 
Fourth  cranial  nerve,  nucleus  of,  247 
Fovea,  center  for,  in  occipital  cortex, 
211 

of  retina,  size  of,  343 
Franklin  theory  of  color  vision,  364 


Freezing-point,  method  of  determin- 
ing, 1035 

Fundic  glands  of  stomach,  774 
Fundus  of  stomach,  725 


GALL-BLADDER,  functions  of,  826 

nerves  of,  827 

Galvanometer,  construction  of,  96 
d'Arsonval,  97 
string,  99 
Gases,  laws  governing  absorption  of, 

678 

of  blood,  674 
pressure  of,  677 
tension  of,  in  solution,  679 
Gas-pump,  674 
Gastric  glands,  774 

histological    changes   in,    during 

secretion  775 
secretory  nerves  of,  780 
secretion,  acid  of,  778 
chemical,  783 
composition  of,  776,  777 
curve  of,  783 
means  of  obtaining,  776 
nervous,  783 

normal  mechanism  of,  781 
Gelatin,  history  of,  as  a  food,  910 

nutritive  value  of,  911 
Genital  organs,  vasomotor  supply  of, 

640 

Germ  plasm,  definition  of,  1020 
Gigantism,  891 

Glans  penis,  sensibility  of,  279 
Gliadin,  nutritive  value  of,  912 
Globin,  427,  1031 
Globulicidal    action   of   blood-serum, 

424 

Globulins,  general  properties  of,  1030 
Glomerulus  of  kidney,  functions  of, 

842 
Glossopharyngeal  nerve,  dilator  fibers 

in,  620 
nucleus,  249 
Glucosamin,  1027 
Glutaminic  acid,  800,  912,  1025 
Gluteins,  1030 
Glutolin,  453 
Glyceric  aldehyde,  917 
Glycin,  799,  912,  1025 
Glycocholic  acid,  822 
Glycocoll,  799,  1025 
Glycogen,  amount  of,  in  liver,  829 
discovery  of,  829 
glycogenic  theory,  832 
importance  of,  in  embryo,  996 
in  muscle,  62,  834 
loss  of,   during  muscular  contrac- 
tions, 67 

metabolism  of,  in  body,  923 
origin  of,  830 


INDEX. 


1047 


Glycogen,  supply  of,  in  body,  915 
Glycogenase,  756 
Glycogenesis,  918 
Glycogenolysis,  834,  918 
Glycoproteins,  1029 
Glycosuria,  918 

alimentary,  808 
Glycylglycin,  1026 
Glyoxylase,  917 
Gmelin's  reaction  for  bile-pigments, 

820 

Goiter,  exophthalmic,  878,  879 
Golgi's  nerve  cells,  second  type,  132 

pericellular  nerve  net,  134 
Graafian  follicle,  structure  of,  981 
Gram-molecular  solution,  1034 
Growth,  1017 
Guanase,  756,  858 
Guanidin  compounds,  parathyroids  in 

regulation  of  metabolism  of,  877 
Guanin,  64,  857 
Guanosin,  859 
Gudden's  commissure,  209,  216 


HARMONY,  physiological  cause  of,  402 
Haustral  churning,  737 
Hearing.    See  Ear. 
cortical  center  of,  211 
limits  of,  402 
Heart,  accelerator  center  for,  599 

nerves  of.  595 
action,  current  of,  545 

of  inhibitory  nerves,  585 
analysis  of  inhibition,  587 
apex-beat  of,  549 

auriculoventricular  bundle,  540,  580 
automaticity  of,  568 
capacity  of  ventricles  of,  561 
cardiac  nerves  of,  course,  585 
cardiogram,  550 
cardio-inhibitory  center  of,  589 
causation  of  beat,  568 
change  in  form  of  ventricle  in  sys- 
tole, 547 

compensatory  pause  of,  580 
coronary  circulation  in,  563 
course  of  cardiac  nerves,  585 
depressor  nerve  of,  618 
diastasis  of,  555 
diastole  and  systole  of,  537 
time  relations  of,  560 
effect  of  calcium  upon,  574 

of  drugs  on,  593 

of  occlusion  of  coronaries  upon, 
565 

of  potassium  upon,  574 

of  sodium  upon,  574 
electrical  changes  in,  545,  698 
escape  from  inhibition,  589 
events  of  a  cardiac  cyle,  559 
fibrillary  contractions,  566 


Heart,  historical  account  of  beat  of, 

569 
inhibition  of  auricle,  589 

of  ventricle,  589 

intra ventricular  pressure  during  sys- 
tole, 551 

intrinsic  nerves  of,  570 
maximal  contractions  of,  577 
musculature  of,  537 
myogenic  theory  of  beat  of,  571 
negative  pressure  in,  564 
neurogenic  theory  of  beat  of,  570 
rate  of  beat  as  affected  by  age,  601 
by  blood-pressure,  601 
by  intrinsic  nerves,  601 
by  muscular  exercise,  602 
by  sex,  600 
by  size,  600 
by  temperature,  603 
reflex  acceleration  of  beat,  597 
refractory  period  of,  579 
sequence  of  beat  of,  544,  580 
sounds  of,  556 
suction-pump  action  of,  564 
systole  and  diastole  of,  537 

time  relations  of,  560 
theories  of  inhibition  of,  593 
third  sound  of,  558 
tonic  inhibition  of,  591 
tonicity  of  muscle  of,  583 
vasomotors  of,  626 
ventricle  of,  in  systole,  547 
ventricular  output  of,  553 
volume  curve  of,  553 
work  done  by,  561 
Heart-beat,  sequence  of,  544 
Heart-block,  582 
Heart-muscle,   general  properties  of, 

57,  577 
Heat  centers,  971 

equivalent  of  foodstuffs,  947 

loss  of,  physiological  regulation  of, 

967 

nerves,  971 
production  in  hydrolysis,  946 

physiological  regulation  of,  969 
regulation,  chemical,  971 
general  statement  of,  967 
physical,  968 
rigor  of  muscle,  54 
sexual,  in  lower  animals,  984 
Heat-stroke,  973 

Helmholtz  theory  of  color  vision,  361 
Helweg's  bundle,  spinal  cord,  181 
Hematin,  428,  437 
Hematoidin,  438 
Hematopoietic  tissue,  439 
Hematoporphyrin,  438 
Hemeralopia  (night-blindness),  360 
Hemianopia  (quadrant),  211 
Hemin,  437 
Hemiplegia,  198 


1048 


INDEX. 


>rption    spectra   of, 


Hemochromogen,  427,  438 
Hemodromograph,  486 
Hemoglobin,    absorptic 
432 

compounds  of,  with  carbon  dioxid, 

430 

monoxid,  430 
nitric  oxid,  429 
oxygen,  429 

condition  of,  in  corpuscles,  421 

crystals  of,  431 

curve  of  dissociation  of  oxyhemo- 
globin,  683 

derivative  compounds  of,  436 

iron  in,  430 

nature  and  amount  of,  427 
Hemolysins,  natural  and  acquired,  424 
Hemolysis,  422 
Hemophags,  439 
Hemophilia,  455 
Hemorrhage,  effect  of,  470 
Heredity,  definition  and  history,  1010 
Hering  theory  of  color  vision,  362 
Hexon  bases,  996 
Hippuric  acid,  860 
Hirudin,  463 
Histidin,  801,  1025 
Histohematins,  438 
Histons,  1007,  1030 
Hof acker-Sadler  law,  1016 
Homoiothermous  animals,  958 
Homolateral  conduction  in  cord,  176 
Hordein,  nutritive  value  of,  911 
Hormones,  783 

stimulation  of  kidneys  by,  849 
Horopter,  375 
Hunger,  sense  of,  290 
Hunger-contractions,  731 
Hydrocele  liquid,  451 
Hydrochloric  acid,  combined,  in  gas- 
tric secretion,  778 
function  of,  in  peptic  digestion, 

786 

in  gastric  juice,  778 
Hydrogel,  453 
Hydrogen  exponent,  416 
Hydrolysis,  754 

heat  energy  of,  947 
Hydrostatic    factor     in     circulation, 

518 

Hyperglycemia,  898,  918 
Hypermetropia,  321 
Hyperpnea,  706 
Hypertension,  887 
Hyperthymusism,  880 
Hypertonic  solutions,  1036 
Hypnotic  sleep,  269 
Hypnotoxin,  266 

Hypoglossal  nerve,  nucleus  of,  250 
Hypotension,  887 
Hypotonic  solutions,  1036 
Hypoxanthin,  64,  856 


IDENTICAL  points  of  retina,  372 
Identity  theory  of  nerve  impulse,  122 
Immune  body,  426 
Incongruence  of  retinas,  373 
Indican,  862 

Indirect  calorimetry,  963 
field  of  vision,  eye,  342 
Indoxyl  sulphuric  acid,  814,  862 
Induction  coil,  24 
Inert  layer  in  circulation,  484 
Inheritance,  Mendelian,  1013 
Inhibition,  escape  from,  in  heart,  589 
of  heart,  585 
of  knee-jerk,  156 
of  reflexes,  147 

of  respiratory  movements,  697 
reflex  of  heart,  590 
theories  of,  593 

Inhibitory  theories  of  sleep,  265 
Inotropic  nerves  to  heart,  589 
Inspiration.    See  also  Respiration. 
definition  of,  649 
increased  heart-rate  during,  668 
means  of  producing,  650 
muscles  of,  652 

Inspired  air,  composition  of,  669 
Intermediary  metabolism  of  carbohy- 
drates, 918 
of  fats,  924 

of  nucleoproteins,  857,  858 
of  proteins,  903 

products  of  muscle  metabolism,  66 
Intermittent  claudication,  34 
Internal  secretion,  adrenals,  881 

definition  and  historical  account, 

873 

liver,  874 
ovary  894 
pancreas,  896 
testis,  893 
thyroid  tissues,  874 
sensations,  273 
Interrenal  system,  882 
Interstitial  cells.  895 

tissue,  893,  1003 

Intestinal  movements,  effect  of  vari- 
ous conditions  upon,  736 
secretion,  804 
villi,  movements  of,  735 
Intestines,  bacterial  action  in,  813 
large,  movements  of,  737 
nervous  control  of  movements  of,  736 
reaction  of  contents  of,  814 
small,  movements  of,  731 
Intracellular  enzymes,  975 
Intracranial  pressure,  632 
Intra-ocular  pressure,  330 
Intrapulmonic  pressure,  661 
Intrathoracic  pressure,  662 
origin  of,  664 

variations  of,  with  forced  breath- 
ing, 663 


INDEX. 


1049 


Intraventricular  pressure,  551 
Introductory  contractions  of  muscle, 

35 

Invertase,  756,  806 
Involuntary  muscle,  55 
lodin   constituent  of   thyroid    tissue, 

879,  880 

lodothyrin,  876,  878,  879 
Iris,  action  of  drugs  upon,  328 

antagonistic  action  of  muscles  upon, 
325 

muscles  and  nerves  of,  324    « 
Iron,  effect  of  removal  of  spleen  on, 
838 

in  hemoglobin,  430 

salts,  source  and  nutritive  impor- 
tance of,  932 
Irritability,  definition  of,  23 

of  muscle,  23 

of  nerve-fibers,  84 
Isodynamic  equivalent  of  foodstuffs, 

951 

Isoleucin,  800, 1025 
Isometric  muscular  contractions,  28 
Isotonic  muscular  contractions,  28 

solutions,  definition  of,  1036 
Isotropous  substance  in  muscle,  20 


JACOBSON,  nerve  of,  758 

Judgments,   visual,    of   distance   and 

size,  381 
perspective  or  solidity,  376 


KENOTOXIN,  70,  672 

Kidney,  action  of  diuretics  on,  846 

blood-flow  through,  847 

composition  of  secretion  of  (urine), 
849 

function  of  convoluted  tubules,  844 
of  glomerulus,  842 

secretion  of  urine  in,  840 

stimulation  of,  by  hormones,  849 

structure  of,  839 
Kinases,  756 
Kjeldahl's  method  for  determination 

of  nitrogen,  852,  900 
Knee-jerk,  conditions  influencing,  159 

definition  of,  155 

explanation  of,  157 

reinforcement  of,  155 

use  of,  as  diagnostic  sign,  160 


LABOR,  physiology  of,  998 
Lactacidogen,  68 
Lactic  acid,  917 

in  muscle,  63 

increase  of,  during  contractions, 

63,67 
Laked  blood,  422 


Langerhans,  islands  of,  897 
Large  intestine,  digestion  and  absorp- 
tion of  food  in,  812 
movements  of,  737 

Larynx,  reflex  effects  from,  on  respi- 
rations, 699 

Latent  period  of  muscular  contrac- 
tion, 27 
Law,  all  or  none,  29 

of    constant    energy    consumption, 

1021 
growth-quotient,  1021 

of  intestine,  732 

of  surface  area,  967 
Lead  sulphid  reaction  for  proteins, 

1029 
Lecithin,  78,  824 

as  complement,  426 
Lecithoproteins,  1032 
Lemniscus,  lateral,  215 

median,  204 
Leucin,  800,  912, 1025 
Leukocytes,     effect     of     hemorrhage 
upon,  471 

functions  of,  444 

structure  and  classification,  443 

variations  in  number  of,  444 
Leydig's  cells,  893 
Liebermann's    reaction   for   proteins, 

1029 
Liebig's    classification    of    foodstuffs, 

941 

Light-reflex  in  eye,  326 
Lipase,  753 

activation  of,  804 

in  pancreatic  secretion,  802 

reversible  reaction  of,  750 
Lipoids,  78 

Lissauer,  tract  of,  168,  169 
Listing's  law,  370 

schematic  eye,  310 
Liver,  acids  of,  821 

bile  pigments  of,  820 

formation  of  urea  in,  835 

glycogen  of,  829 

glycogenic  action  of,  832,  833 

internal  secretion  of,  874 

pulse,  532 

quantity  of  bile,  819 

secretion  of  bile,  824 
Localization  of  function  in  cerebellum, 

243 

in  cerebrum,  192 
Localizing  power  of  skin,  284 
Locke's  solution,  575 
Locomotor  ataxia,  171 
Ludwig  theory  of  urinary  secretion, 

840 

,  Luminosity  of  visual  sensations,  347 
I  Lungs,  gaseous  exchanges  in,  686 

total  surface  of,  649,  688 

vasomotors  of,  627 


1050 


INDEX. 


Lymph,  action  of  lymphagogues,  477 

circulation  of,  642 

formation  of,  476 

summary  of  factors  concerned  in 

formation  of,  481 
Lymphoblasts,  444 
Lymphocytes,  443 
Lysin,  800,  912,  1025,  1031 


MACROPHAGS,  439 

Macular  field,  343 

Maltase,  756,  771,  802,  806 

Maltose,  772,  802 

Mammary  glands,  conditions  control- 
ling secretion  of,  999 
structure  and  function-,  9G9 

Manometer,  Hiirthle's,  497 

maximum  and  minimum,  497 
use  of,  for  determining  blood-pres- 
sure, 491 

Mast-cells,  444 

Mastication,  719 

Mathematical  perspective,  377 

Mean  blood-pressure,  496 

Medulla  oblongata,  245 
physiology  of,  882 
respiratory  center  in,  691 

Medullary  striae,  215 

tissue,  functional  significance  of,  886 

Meionectic  blood,  684 

Mendelian  iaw  of  inheritance,  1013 

Meningeal  spaces,  630 

Menstruation,  1013 

effect  of,  on  other  functions,  987 
physiological  significance  of,  987 

Mercury  manometer,  use  of,  for  blood- 
pressures,  491 

Mesectic  blood,  684 

Metabolism,  basal,  966 
definition  of,  899 

intermediary,  of  carbohydrates,  918 
of  fats,  924 
of  nucleoproteins,  858 
of  proteins,  903 

Metaproteins,  1032 

Metathrombin,  464,  465 

Methemoglobin,  436 

Methylglyoxal,  917 

Methylpurins,  857 

Microphage,  445 

Micturition,  physiology  of,  863 

Milk,  composition  of,  1001 

Million's  reaction  for  proteins,  1028 

Minimal  air,  658 

Miosis,  definition  of,  328 

Molisch  reaction  for  proteins,  1029 

Monakow's  bundle,  180 

Motor  aphasia,  219 
areas  of  brain,  196 
paths  in  spinal  cord,  178 
points  in  man,  92 


Mountain  sickness,  689,  713 
Movements  of  alimentary  canal,  defe- 
cation, 739 
deglutition,  719 
large  intestine,  737 
mastication,  719 
small  intestine,  731 
stomach,  726 
vomiting,  741 
Mucin  in  saliva,  761 
Muscarin,  action  of,  on  heart,  593 

on  iris,  328 

on  sweat-glands,  870 
Muscle,  absolute  power  of,  39 
action  current  of,  102 
artificial  stimulation  of,  24 
carbohydrates  of,  62 
cardiac,  properties  of,  57,  577 
chemical  changes  of,  in  contraction 

65 

composition  of,  60 
compound  contractions  of,  42 
contraction  of,  25 

wave  of,  36 
contracture  of,  32 
curve  of  work  of,  41 
death  rigor,  52 
demarcation  current  of,  95 
direct  irritability  of,  23 
disappearance  of  glycogen  in,  66 
effect  of  temperature  upon,  29 

of  veratrin  upon,  31 
efficiency  of,  as  work-machine,  38 
energy  liberated  in,  37 
Englemann's  artificial,  71,  72 
enzymes  of,  64 
ergographic  records  from,  48 
extensibility  and  elasticity  of,  20 
fatigue  of,  35,  50,  69 
glycogen  of,  834 
heat  rigor  of,  54 
inorganic  salts  of,  64 
introductory  contractions  of,  35 
isotonic  and  isometric  contractions 

of,  28 

lactic  acid  of,  63 

latent  period  of  contraction  of,  27 
maximal  and  submaximal  contrac- 
tions of,  29 

myogenic  tonus  of,  57 
neurogenic  tonus  of,  56 
nitrogenous  extractives  of,  60,  63 
number    of    stimuli    necessary   for 

tetanus,  45 
pale  fibers  in,  19,  26 
pigments  of,  64 
plain,  55 
plasma,  19,  60 

production  of  carbon  dioxid  in,  64 
proteins  of,  60 
red  fibers  in,  19,  26 
sarcoplasm,  19 


INDEX. 


1051 


Muscle,  simple  contraction  of,  25 
smooth,  55 
stroma,  61 
structure  by  polarized  light,  19 

of  fiber,  IS 

summation  of  contractions  of,  44 
theories  of  nature  of  contraction, 

71 

tone  of,  during  contraction,  44 
tonicity  of,  51 
vasomotor  supply  of,  641 
voluntary  contractions  of,  46- 
white  and  red  fibers  of,  19 
Muscle-sense,  cortical  area  for,  203 
importance  of,  in  visual  judgments, 

377 

paths  for,  in  spinal  cord,  172,  174 
quality  of,  289 

Muscular  contraction,  electrical  varia- 
tion in,  105 
intermediary   chemical   products 

in,  65 

insufficiency  in  movements  of  eye- 
balls, 370 

or  deep  sensibility,  288 
work,  effect  of,  on  heart-rate,  602 
on  physiological  oxidations,  941 
on  protein  metabolism,  942 
on  respiratory  movements,  710 
Musical    sounds,     classification    and 

properties  of,  394 
Mutations,  theories  of,  1012 
Mydriasis,  definition  of,  328 
Myelin  sheath  of  nerve-fibers,  func- 
tion of,  76 
Myelinization    method    of    Flechsig, 

164,  226 

Myeloblasts,  444 
Myenteric  reflex,  732 
Myofibrillae  (of  plain  muscle),  55 
Myogen,  61 
fibrin,  61 
Myogenic  theory  of  heart-beat,  571 

tonus,  57 
Myohematin,  438 
Myopia,  320 
Myosin,  61 
fibrin,  61 
Myxedema,  875 


NARCOSIS,  effect  of,  upon  nerve  im- 
pulse, 115 

Near  point  of  distinct  vision,  316 

Negative  pressure  in  thorax,  662,  664 

in  ventricle,  564 

variation  in  muscle  and  nerve,  102, 
103 

Nerve,  abducens,  nucleus  of,  249 
auditory,  213 

chorda  tympani,  294,  759,  761 
facial,  nucleus  of,  249 


Nerve,  fourth  cranial  nucleus  of,  247 

glossopharyngeal,  nucleus  of,  249 

hemorrhoidalis  inferior,  739 

hypoglossal,  nucleus  of,  250 

motor  and  sensory  roots  of,  81 

olfactory,  216 

optic,  208 

pudendus,  739 

recurrent,    sensibility    of    anterior 
roots,  82 

secretory,  of  adrenal  glands,  886 

spinal  accessory,  nucleus  of,  250 

third  cranial,  nucleus  of,  246 

trigeminal,  nucleus  of,  247 

twelfth  cranial,  nucleus  of,  250 

vagus,  nucleus  of,  249 
Nerve-cell,  chromatolysis  of,  127 

classification  of,  in  spinal  cord,  162 

degenerative  changes  in,  126 

general  physiology  of,  135 

internal  structure  of,  134 

metabolism  in,  138 

neuron  doctrine,  129 

reaction  of,  136 

refractory  period  of,  139 

summation  of  stimuli  in,  138 

varieties  of,  131 
Nerve-fibers,  action  current  of,  102 

afferent  and  efferent,  79 

anodal  and  cathodal  stimulation  of, 
87 

antidromic  impulses  in,  82 

artificial  stumuli  of,  84 

autoregeneration  of,  126 

chemistry  of,  77 

classification  of,  80 

core  model  of,  108 

degeneration  and  regeneration  of, 
124 

demarcation  current  of,  95 

direction  of  conduction,  113 

du  Bois-Reymond's  law  of  stimu- 
lation, 86 

electrical  stimulation  of,  in  man,  93 

electrotonic  currents  of,  107 

electrotonus  of,  87 

impulse  in,  historical,  109 

independent  irritability  of,  84 

metabolism  in,  during  activity,  118 

myelin  sheath  of,  76 

nutritive   relations    to    nerve-cells, 
123 

opening  and  closing  tetanus  of,  90 

Pfluger's  law  of  stimulation  of,  92 

stimulation  of,  in  man,  90 

structure  of,  75 

unipolar  method  of  stimulating,  91 
Nerve-impulse,  historical,  109 

metabolism  during,  118 

modification  of,   by  various  influ- 
ences, 114 

qualitative  changes  in,  80,  121 


1052 


INDEX. 


Nerve-impulse,  relation  of,  to  action 
current,  105,  113 

theories  of,  119 

velocity  of,  110 
Nervi  erigentes,  256,  621,  640 
Nervous  secretion,  gastric,  783 

pancreatic,  797 
Neurogenic  theory  of  heart-beat,  570 

tonus,  56 

Neuron  doctrine,  129 
Neurons,  varieties  of,  131 
Nicotin,  action  of,  on  salivary  secre- 
tion, 768 
on  sweat  secretion,  870 

use  of,  in  tracing  autonomic  fibers, 

254 

Night-blindness,  hemeralopia,  360 
Ninhydrin  reaction  for  protein,  1028 
Ninth  cranial  nerve,  nucleus  of,  249 
Nissl's  granules,  134 
Nitric  oxid  hemoglobin,  430 
Nitrogen,  condition  of,  in  blood,  681 

determination  of,  900 

equilibrium,  899 

effect  of  non-protein  food  on,  902 

excretion  in  urine,  851 
Nitrogenous  extractives  of  muscle,  64 
Nodal  point  of  eye,  312 
Non-polarizable  electrodes,  100 
Norleucin,  800 
Normoblasts,  440 
Nuclease,  756 

Nucleo-albumin  in  bile,  824 
Nucleoproteins,  1031 

in  blood,  453 

intermediary  metabolism  of,  858 


OBESITY,  physiological  cause  of,  928 
Ohm's  law  of    composition   of   sound 

waves,  397 
Olfaction,  end-organ  for,  299 

mechanism  of,  300 
Olfactometer,  304 
Olfactory  associations,  305 

bulb,  histological  structure  of,  217 

center  in  cortex,  216 

nerve,  course  of  fibers  of,  in  brain, 
218 

organs,  fatigue  of,  303 

sensations,  classification  of,  301 
conflict  of,  305 
qualities  of,  301 
threshold  stimulus,  303 

sense  cells,  300 

stimuli,  nature  of,  301 
Oncometer,  847 
Oocytin,  994 
Oogonia,  991 
Ophthalmometer,  334 
Ophthalmoscope,  331 
Opotherapy,  873 


Opsonins,  445 

Optic  chiasma,  decussation  in,  209 
nerve,  course  of  fibers  of,  in  brain, 

208 

radiation,  209 
thalamus,   functions   of,   in   vision, 

212 
tracts,  structure  of,  209 

Optical  deceptions,  382 

Optograms  on  retina,  339 

Orokinase,  771 

Orthodiagram,  549 

Orthodiagraph,  549 

Osmosis,  definition  of,  1032 

Osmotic  pressure,  definition  of,  1033 
determination  of,  1035 
of  blood,  423 

Oval  field  of  Flechsig,  180 

Ovaries,  internal  secretion  of,  894 
relation  of,  to  menstruation,  986 

Overtones,  production  of,  397 

Ovulation,  982 

Ovum,  fertilization  of,  992 

implantation  of,  in  uterus,  994 
maturation  of,  990 
passage  of,  into  uterus,  989 

Oxalate  solutions,  effect  of,  on  coagu- 
lation, 468 

Oxalated  plasma,  465 

Oxidases,  754,  973 

Oxidations,  theories  of,  973 

Oxygen,    action    of,    on    respiratory 

center,  702,  711 

compound  of,  with  hemoglobin,  429 
condition  of,  in  blood,  681 
effects  of  varying  pressures  of,  on 

respiration,  711 
potassium  ferricyanide  method  of 

determining,  676 
tension  of,  in  alveolar  air,  686 
in  tissues,  688,  689 
in  venous  blood,  686 

Oxygenase,  976 

Oxygen-pressure  of  blood,  690 

Oxyhemoglobin,  429 

Oxyprolin,  801, 1025 

Oxyproteic  acid,  853 

Oxypurins,  857 


PACCHIONIAN  bodies  of  brain,  631 
Pain  sense,  distribution  and  charac- 
teristics of,  286 
localization  of,  287 
path  for,  in  cord,  174 
Pains,  hunger-,  731 
Pale  fibers  of  muscle,  19,  26 
Pancreas,  action  of  lipase  in,  803 
anatomy  of,  793 
curve  of  secretion  of,  795 
digestive  action  of  secretion,  798 
on  carbohydrates,  803 


INDEX. 


1053 


Pancreas,  internal   secretion  of,  896, 
898 

normal  mechanism  of  secretion,  796 

secretory  nerves  of,  794 
Pancreatic  secretion,  chemical,  797 

nervous,  797 
Paraglobulin,  451 
Paralysis  (motor),  198 
Paralytic  secretion  (saliva),  769 
Parapeptone,  786 
Paraphasia,  220 
Parathyroid,   structure  and  function 

of,  875,  876 
Parthenogenesis,  994 
Parturition,  physiology  of,  998 
Past  pointing,  408 
Pellagra,  955 
Pendular  movements  (intestine),  732 

sound  waves,  395 
Pepsin,  784 

discovery  of,  748 

properties  of,  784 
Pepsin-hydrochloric     acid     digestion, 

786 

Peptids,  802,  1026 
Peptone,  786 

absorption  of,  in  stomach,  792 

effect  on  clotting  of  blood,  469 
Peptonised  blood,  464 
Peptozym,  469 
Pericardial  liquid,  451 
Perimeter,  342 
Peripheral  field  of  vision,  342 

pulse,  529 

resistance  in  circulation,  517 
Peristalsis,  732 
Peroxidases,  976 
Perspiration.    See  Sweat. 
Pettenkofer's  reaction,  822 
Pfltiger's  law  of  stimulation,  88 

tetanus,  90 
Phagocytes,  445 
Phenolsulphuric  acid,  862 
Phenomenon  of  conditioned  reflexes, 

190 

Phenylalanin,  800,  1025 
Phlorhizin  diabetes,  921 
Phosphatids,  78  • 
Phosphoproteins,  1032 
Phrenology,  192 
Phenosin,  79 

Physical  heat,  regulation,  968 
Physiological  diplopia,  373 

oxidations,  theories  of,  973 
Lavoisier's  work,  645,  957 

point  (vision),  344 

saline,  424 

Physostigmin,  action  of,  on  iris,  328 
Pilocarpin,  action  of,  on  heart,  593 
on  iris,  328 

on  salivary  glands,  253 
on  sweat  glands,  870 


|  Pineal  body,  892 

1  Pinealectomy,  effects  of,  893 

Piqiire,  918 

Pituitary  body,   structure  and  func- 
tions of,  888,  892 
effects  of  removal  of,  891 
extracts  of  anterior  lobe  of,  890 
of  posterior  lobe  of,  890 

Placenta,  functions  of,  995 

Plain  muscle,  55 

Plasma  of  blood,  composition  of,  449 

Pleonectic  blood,  684 

Plethysmography,  608 

Pneumogastr,ic  nerve.    See  Vagus. 

Pneumograph,  655 

Pneumothorax,  665 

Poikilothermous  animals,  958 

Pointing  error  test,  408 
past,  408 

Polar  bodies  of  ovum,  991 

Polypeptid,  802,  1026 

Positive  electrical  variation  in  heart, 
594 

Posterior  funiculi,   descending  tracts 

of,  177,  180 
tracts  of,  169 
root,  cells  of,  origin  of,  83 
ganglia,  type  of  cells  in,  131 
termination  in  cord,  .168 

Postganglionic  nerve-fibers,  252 

Potassium  ferricyanide  method  of  de- 
termining oxygen,  676 
salts,  action  of,  on  heart,  574,  605 

Potential  energy  of  food,  946 

Precipitins,  1027 

Predicrotic  pulse-wave,  528 

Preganglionic  nerve-fibers,  252 

Pregnancy,  changes  in,  997 

Prepyramidal  tracts,  180 

Presbyopia,  316,  321 

Press- juice,  752 

Pressor  nerve-fibers,  615 

Pressure  of  gases  in  solution,  679 

'    sense,  deep,  279 

distribution  of,  283 
localizing  power,  etc.,  284 

Primary  proteoses,  786 

Principal  axis  of  lens,  307 
focal  distance,  307 

Projection  system  of  fibers  (brain),  185 

Prolamines,  1030 

Prolin,  801,  912,  1025 

Propeptone,  786 

Prostate  gland,  1005,  1008,  1009 

Protalbumoses,  786 

Protamins,  1006,  1030 

Protanopia,  355 

Proteases,  753 

Protective  enzymes,  754 

Proteins,  absorption  of,  in  intestine, 

811 
adequate,  910 


1054 


INDEX. 


Proteins  as  glycogen  formers,  831 

biologic  value  of,  904 

circulating,  905 

classification  of,  1029 

definition  and  structure  of,  1025 

diffusion  of,  1037 

excretion  of  nitrogen  of,  851,  852, 
853 

general  reactions  of,  1027 

in  blood-plasma,  450 

inadequate,  910 

necessary  amount  of,  in  diet,  906, 
949,  950,  951 

normal  metabolism  in  body,  903 

nutritive  value  of,  909 

of  muscle,  60 

osmotic  pressure  of,  1036 

putrefaction  of,  in  large  intestine, 
814 

specific  dynamic  action  of,  914 

storage,  905 

synthesis  of,  in  body,  811 
Proteolytic  enzymes,  753 
Proteoses,  1032 

general  properties  of,  787 
Protopathic  sensations,  279 

sensibility,  278 

Proximate  principles  of  food,  744 
Psychophysical  law,  275 
Ptomaines.  815 
Ptyalin,  761 

action  of,  in  stomach,  730,  773 

digestive  action  of,  771 

effect  of  various  conditions  upon, 

773 

Pubertal  gland,  894,  1003 
Puberty,  983,  1003 

Pulmonary    arteries,    vasomotors   of, 
627 

circulation,  peculiarities  of,  521 

variations  of,  pressure  in,  522 
Pulse,  anacrotic  waves  of,  529 

catacrotic  waves  of,  528 

central,  529 

form  of  wave,  527 

general  statement,  523 

peripheral,  529 

varieties  of,  in  health  and  disease, 
530 

velocity  of  propagation  of,  524 

venous,  531 
Pulse-pressure,  495 
Pulsus  irregularis  perpetuus,  566 
Purin  bases,  63,  856 
Purkinje  fibers,  545 

images  of,  314 

phenomenon,  349 
Putrefaction  in  intestines,  814 
Pyloric  glands  of  stomach,  774 

secretion  of.  785 
Pyramidal  tract  in  brain,  197 
in  spinal  cord,  178 


Pyrrol  compounds  in  protein  mole- 
cule, 801 
Pyrrolidin-carboxylic  acid,  801,  1025 


QUADRANT  hemianopia,  211 
Quotient,  respiratory,  714 


REACTION  of  degeneration,  93 

time,  111 

Reactions,  biological,  425 
for  proteins,  1027 
Gmelin's,  820 
of  blood,  416 

of  contents  of  small  intestine,  813 
of  urine,  849 
Pettenkofer's,  822 

Recessive   characteristics   in   inherit- 
ance, 1013 

Reciprocal  inneryation,  148 
Recurrent  sensibility  of  anterior  roots, 

82 

Red  blood-corpuscles,  chemical  com- 
position of,  449 

condition  of  hemoglobin  in,  421 
effect  of  hemorrhage  upon,  439 
hemolysis  of,  422 
number  and  size  of,  421 
origin  and  fate  of,  438 
variations  in  number  of,  440 
fibers  in  muscles,  19,  26 
Reduced  hemoglobin,  429 

schematic  eye,  310 
Reflex  actions,  axon  reflexes,  151 
classification  of,  142 
conditioned,  190 
definition  and  historical,  140 
deep,  160 

unconditioned,  190 
extensor  thrust,  158 
from  parts  of  brain,  149 
influence  of  condition  of  cord  on, 

149 

of  sensory  endings  upon,  145 
inhibition  of,  147 

of  heart,  590 
knee-jerk,  155 
myenteric,  732 

of  erection  and  ejaculation,  1008 
of  respiratory  center,  694,  698 
of  vasomotor  nerves,  615 
preparation  of  reflex  frog,  142 
reflex  arc,  141 
respiratory,    from    nose,    larynx, 

and  pharynx,  699 
special  and  deep  reflexes  of  cord, 

160 

spinal  reflexes,  142 
theory  of,  144 

through  peripheral  ganglia,  150 
vasodilator  nerves,  622 


INDEX. 


1055 


Reflex  extensor,  time  of,  146 

Turck's  method  of  studying,  149 
special  spinal,  160 
spinal,  142 

Refractive  power  of  eye,  317 
Refractory  period  of  heart-beat,  579 
of  nerve-cell,  139 
of  nerve-fiber,  118 
Regeneration  in  nerve-fibers,  124 
Reinforcement  of  knee-kick,  155 
Reproduction,   changes  during  preg- 
nancy, 997 

in  uterus  in  menstruation,' 984 
chemistry  of  spermatozoa,  1006 
determination  of  sex,  1015 
erection,  1007 
fertilization  of  ovum,  992 
functions  of  placenta,  C95 
general  statements,  980 
growth  and  senescence,  1017 
heredity,  1010 
implantation  of  ovum,  994 
mammary  glands,  999 
menstruation,  983 
nutrition  of  embryo,  995 
ovulation,  981 
parturition,  998 

properties  of  spermatozoa,  1004 
relation  of  ovaries  to  menstruation, 

985 
structure  and  functions  of  corpus 

luteum,  981 

of  Graafian  follicles,  981 
Residual  air,  658 

Resonance,    importance  of,   in   func- 
tions of  ear,  398 

Respiration,  abdominal  type,  654 
acapnia,  708,  714 
accessory  centers  of,  in  brain,  701 

respiratory  movements,  655 
anatomy  of  thorax,  648 
apnea,  706 
artificial,  659,  668 
asphyxia,  707 
aspiratory  action  of,  on  blood-flow, 

665 
automatic     action     of    respiratory 

center,  693 

bronchoconstrictor     and     broncho- 
dilator  fibers,  709 
calorimeter,  963 
capacity  of  the  bronchi,  658 
chamber,  901 
chemical    composition    of    inspired 

and  expired  air,  669 
Cheyne-Stokes  type  of,  716,  717 
complemental  air,  658 
condition  of  carbon  dioxid  in  blood, 

684 

costal,  654 

definition  of  inspiration  and  expira- 
tion, 649 


Respiration,  dissociation  of  oxyhemo- 

globin,  683 
dyspnea,  653,  706 
effect  of  anemia  upon,  717 

of  changes  in  barometric  pressure 

upon,  713 
in  composition  of  air,  711 

of  muscular  work  upon,  710 
exchange  of  gases  in,  669 
forced,  653 

gaseous  exchange  in  lungs,  686 
gases  of  blood,  674 
history  of,  644 
hyperpnea,  706 

increased  heart-rate  during  inspira- 
tion, 580 
injurious  effect  of  the  expired  air, 

670 

intrapulmonic  pressure,  661 
intrathqracic  pressure,  662 
mechanism  of  inspiration,  650 
methods  of  recording,  655 
minimal  air,  658 
modified,    respiratory    movements, 

716 

mountain  sickness,  713 
muscles  of  expiration,  652 

of  inspiration,  652 
negative  pressure  in  thorax,  663 
normal  stimulus  of,  701 

of  swallowing,  721 

ventilation  of  alveoli,  659 
origin     of     negative     pressure     in 

thorax,  664 

physical  theory  of,  685 
physiological  anatomy  of  organs  of, 

648 

pneumothorax,  665 
reflex    stimulation    of    respiratory 

center,  694 

relation  of  vagus  nerve  to,  695 
residual  air,  658 
respiratory  center,  691 

quotient,  714 

waves  of  blood-pressure,  666 
secretion  of  gases  in  lungs,  688 
spinal  respiratory  centers,  692 
supplemental  air,  658 
tension  of  gases  in  alveolar  air,  687, 

688 

in  arterial  blood,  688 
in  tissues,  688 
in  venous  blood,  687,  688 
tidal  air,  657 
value  of  nitrogen  in,  681 
ventilation,  principles  of,  670 
vital  capacity,  657 
volumes  of  air  respired,  656 
voluntary  control  of,  699 
Respiratory  center,  691,  700 

automatic  activity  of,  693 

normal  stimulus  of,  701 


1056 


INDEX. 


Respiratory  center,  reaction  of,  to 
change  in  carbon  dioxid  pres- 
sure, 703 

to  oxygen  pressure,  703,  704 
reflex  stimulation  of,  705 
movements,   electrical   changes  in, 

698 

quotient,  714 

waves  of  blood-pressure,  666 
Restiform  body,  235 
Retina,  action  current  of,  337 
acuity  of  vision  in,  343 
after-images  from,  352 
color-blindness  of,  354 
contrasts  in,  353 
vision  in,  349 

corresponding  points  of,  372 
distribution  of  color  sense  in,  357 
entoptic  phenomena,  366 
function  of  rods  and  cones  of,  358 
fundamental    and    complementary 

colors,  351 
light   adapted   and   dark   adapted, 

346 

portion  of,  stimulated  by  light,  336 
projection    of,   on    occipital   lobes, 

210 
qualities  of  visual  sensations  from, 

349 

size  of  fovea  in,  343 
theories  of  color  vision  in,  360 
threshold  stimulus  of,  345 
visual  purple  of,  338 
Retinoscope,  333 

Reversible  chemical  reactions,  750 
Rheoscopic  frog  preparation,  104 
Rhodopsin,  338 

Ribs,  action  of,  in  inspiration,  651 
Rice,  relation  to  beri-beri,  913 
Rigor  of  muscle,  52,  68 
Ringer's  solution,  574 
Ritter's  tetanus,  90 
Rivinus,  ducts  of,  758 
Rods  and  cones  of  eye,  functions  of, 

358 

Romberg's  symptom,  240 
Rubner's  laws  of  growth,  1021 

surface  area  law,  966 
Rubrospinal  tract,  180,  199 


SACCULUS,  functions  of,  412 
Sacral  autonomies,  739,  740 
Saliva,  chorda,  762 

composition  of,  761 

digestive  action  of,  761 

general  functions  of,  773 

secretory  nerves  for,  761 

sympathetic,  762 
Salivary  glands,  action  of  drugs  upon, 

768 
anatomical  relations,  758 


Salivary  glands,  histological  changes 

during  activity,  765 
structure  of,  758 
normal  stimulation  of,  769 

secretory  centers  for,  770 

nerve-fibers  of,  762 
theory  of  secretory  nerves,  764 
Salts,  absorption  of,  in  stomach,  792 

excretion  of,  863,  932 

general  nutritive  importance  of,  932 
Sarcolactic  acid,  63 
Sarcostyles,  19 

Sebaceous  glands,  secretion  of,  871 
Secondary  axes  of  a  lens,  308 

degeneration,  nerve-fibers,  123,  164 

proteoses,  786 
Secretin,  gastric,  782 

pancreatic,  797 
Secretion,  758 

internal,  873 

paralytic  (saliva),  769 

of  bile,  824 

of  gastric  juice,  780 

of  intestinal  juice,  804 

of  pancreatic  juice,  794 

of  saliva,  761 

of  sebaceous  glands,  871 

of  sweat,  867 

of  urine,  840 

Secretogogues  of  gastric  glands,  782 
Secretory  nerves  of  salivary  glands, 

761 

Semicircular   canals,    direct   stimula- 
tion of,  407 

Fluorens'  experiments  upon,  405 
structure  of,  404 
temporary  and  permanent  effects 

of  operations  on,  406 
theories  of  functions  of,  409 
Seminal  vesicles,  function  of,  905 
Senescence,  1017 
Senses,  classification  of,  271 

cutaneous  and  internal,  278 
Sensibility,  muscular,  288 

of  glans  penis,  279 

protopathic  and  epicritic,  278 
Sensory  aphasia,  221 

areas  of  cortex,  202 

paths  in  spinal  cord,  169,  172 
Sequence  of  heart-beat,  544,  580 
Serin,  799,  1025 
Serodiagnosis,  754 
Serozym,  463 

Serum,  action  of  foreign,  424 
Serum-albumin,  450 
Serum-globulin,  451,  1030 
Seventh  cranial  nerve,  nucleus  of,  249 
Sex,  determination  of,  1015 
Sexual  infantilism,  891 
Side-pressure  in  blood-vessels,  513 
Sino-auricular  node,  541,  572 
Sinospiral  fibers  of  heart,  539 


INDEX. 


1057 


Sixth  cranial  nerve,  nucleus  of,  249 
Skatoxylsulphuric  acid,   862 
Skeletal  muscular  tissue,  structure  of, 

17 

Skiascope,  333 
Skin,  excretory  functions  of,  867 

sweat  glands  of,  867 
Sleep,  changes  in  circulation  during, 

261 

curves,  intensity  of,  260 
effect  of  sensory  stimulation  during, 

264 

hypnotic,  269 
metabolism  during,  944 
physiological  phenomena  of,  258 
theories  of,  265 

Small  intestine,  absorption  in,  806 
Smegma  prseputii,  871 
Smell,  center  for,  in  brain,  216 

end-organ  of,  299 
Smelling,  mechanism  of,  300 
Sodium  chlorid,  nutritive  value  of,  932 

salts,  effect  of,  on  heart-beat,  574 
Somatoplasm,  definition  of,  1020 
Sound,  sensations  of.    See  Ear. 
waves,  nature  and  action  of,  394 
overtones  of,  397 
simple  and  compound,  395 
Specific  energy  of  taste  sensations,  297 
gravity  of  blood,  420 
nerve  energies,  doctrine  of,  121,  273 

of  cutaneous  nerves,  281 
Spectra,  absorption,  blood,  432 
Spectroscope,  433 
Spermatozoa,  chemistry  of,  1006 
maturation  of,.  1004 
properties  of,   1004 
Spherical  aberration  in  eye,  319 
Sphincter,  cardiac,  724 
external,  of  anus,  739 
ileocecal,  737 
internal,  of  anus,  739 
of  bile-duct,  827 
of  bladder,  864 
Sphygmography,  526 
Sphygmomanometers  for  determining 

blood-pressure  in  man,  503 
Spinal  cord  as  path  of  conduction,  162 
classification  of  tracts  in,  165 
effect  of  removing,  153 
general    relations    of    gray    and 

white  matter  in,  164 
groups  of  cells  in,  162 
Helweg's  bundle  in,  181 
homolateral     and     contralateral 

conduction  in,  176 
less  well-known  tracts  of,  180 
Monakow's  bundle  in,  180 
paths  in,  for  cutaneous  impulses, 

174 

pyramidal  tracts  of,  180 
reflex  activities  of,  140 

67 


Spinal  cord,  tonic  activity  of,  152 
tracts  of,  in  lateral  funiculi,  172 
in  posterior  funiculi,  169 
in  white  matter,  165 
vestibulospinal  tract,  181,  235 

reflex  movements,  142 

reflexes,  142 

in  mammals,  145 

respiratory  center,  692 
Spirometer,  657 
Spleen,  physiology  of,  836 
Stannius,  first  ligature  of,  582 
Stapedius  muscle,  function  of,  390 
Starvation,  effect  of,  on  body-metab- 
olism, 945 

Steapsin.     See  Lipase. 
Stenson's  duct,  758 
Stereognostic  perception,  204 
Stereoscopic  vision,  378 
Stethoscope,  556 
Stifel's  figure,  336 
Stimulants,  747 

nutritive  importance  of,  935 
Stimuli,  artificial,  of  muscle,  24 

of  nerve,  84 

Stokes-Adams  syndrome,  582 
Stokes'  reducing  agent,  435 
Stomach,  absorption  in,  791 

anatomy  of,  725 

automaticity  of,  730 

digestion  in,  790 

glands  of,  774 

histological     changes     in,     during 
activity,  775 

means  of  obtaining  secretion  of,  776 

mechanism  of  gastric  secretion,  781 

movements  of,  726 

musculature  of,  726 

properties  of  pepsin  of,  784 

secretory  nerves  of,  780 
Storage  proteins,  905 
Strabismus,  370 
String  galvanometer,  99 
Stromuhr,  485 
Subliminal  stimulus,  346 
Submaxillary  ganglion,  758 
Substrata,  752 
Succus  entericus,  804 
Sugar  puncture,  918 

regulation  of  supply  of,  in  body, 

918 

Sugars.     See  Carbohydrates. 
Sulphur,  forms  in  which  excreted,  861 
Summation  of  muscular  contractions, 
43 

of  stimuli  in  nerve-centers,  138 
Superior  olivary  body,  relation  of,  to 

auditory  paths,  215 
Supplemental  air,  658 
Surface  area  law,  966 
Swallowing,  719 

respiration,  721 


1058 


INDEX. 


Sweat,   amount  and  composition   of, 

867 

nerve-centers  for,  870 
nerves,   action  of,  in  heat  regula- 
tion, 968 

secretory  fibers  of,  869 
Sympathetic  nervous  system,  general 

relations,  251 
resonance,  398 
Syntonin,  787 

Systole,  duration  of,  in  heart,  560 
Systolic  arterial  pressure,  495 

determination  of,   in  animals, 

497 
in  man,  503 


TABES  dorsalis,  171 
Tactile  discrimination,  175 

localization,  287 
Taste  buds,  296 

center  for,  in  brain,  218 

nerves  of,  294 

sensations,  classification  of,  296 
specific,  energy  of,  297 
threshold  stimulus,  299 

sense  of,  294 

stimuli,  mode  of  action,  298 
Tectorial  membrane,  400 
Temperature.   See  Heat. 

coefficient,  114 

effect  of,  on  body  metabolism,  944 
on  gases  in  solution,  677 
on  heart-rate,  604 
on  muscular  contraction,  29 

of  human  body,  959 

sense,    distribution   and   character- 
istics, 280,  282 
path  for,  in  spinal  cord,  174 
punctiform  distribution  of,  280 
Tension  of  gases  in  solution,  679 
Tensor  tympani  muscle,  function  of, 

394 

Tenth  cranial  nerve,  nucleus  of,  249 
Testis,  internal  secretion  of,  893 
Tetanus,  number  of  stimuli  necessary 
for,  45 

of  muscle,  42 

opening  and  closing,  90 
Tethelin,  891 
Theobromin.  857,  936 
Third  cranial  nerve,  nucleus  of,  246 

heart  sound,  558 
Thirst,  sense  of,  293 
Thoracic  autonomies,  739,  740 
Thorax  as  cloSed  cavity,  648 

aspiratory  action  of,  665 

normal  position  of,  649 

origin  of  negative  pressure  in,  664 
Thrombin,  457 

method  of  obtaining,  458 
Thrombogen,  458 


Thrombokinase,  462 
Thromboplastic  substances,  461 
Thrombosis,  455 
Thyroid,  extirpation  of,  875 

function  of,  878 

internal  secretion  of,  874 
Thyro-oxy-indol,  879 
Thyrotoxin,  879 
Tidal  air,  657 

Tigroid  substance  in  nerve-cells,  134 
Tissue  protein,  904 
Tissues,  exchanges  of  gases  in,  688 
Tone  (musical)  of  muscular  contrac- 
tion, 44 
Tonicity  of  heart-muscle,  583 

of  muscle,  51 

of  nerve-centers,  153 
Tonometer,  680 
Tonus,  myogenic,  57 

neurogenic,  56 

Touch  sense,  path  of,  in  cord,  174 
Tract  of  Lissauer,  168,  169 
Tracts  in  cerebellum,  235 

in  spinal  cord,  165 

of  Flechsig,  167 

of  Cowers,  167 

of  Helweg  (olivospinal),  181 

of  Monakow  (rubrospinal),  180,  199 
Traube-Hering  waves,  620 
Treppe  in  muscular  contractions,  35 
Trigeminal   nerve,    area   of   distribu- 
tion of,  247 
nucleus  of,  247 
Tritanopia,  355 
Trophic  nerve-fibers,  salivary  glands, 

764 

Trypsin,  753,  798 
Tryptophan,  801,  912 
Tiirck's  method  for  reflex  time,  149 
Twelfth    cranial    nerve,    nucleus    of, 

251 

Tympanic  membrane,  386 
Tyrosin.  800,  912,  1025 

reagent,  1028 

UNCONDITIONED  reflexes,  190 
Unipolar  method  of  stimulation,  91 
Unitarian   theory    (blood-corpuscles), 

444 
Urea,  formation  of,  in  liver,  835 

origin  and  significance  of,  853,  1025 
Ureters,  contractions  of,  863 
Urethra,  sphincter  of,  864 
Uric  acid,  63,  856 
in  spleen,  838 
significance  of,  856 
Uricolytic  enzyme,  859 
Urinary  bladder,  movements  of,  864 
nerves  of,  866 

pigments,  851 
Urination,    physiological    mechanism 

of,  863 


INDEX. 


1059 


Urine,  composition  of,  849 
nitrogenous  excreta  of,  851 
origin  of  acidity  of,  846,  849 
reaction  of,  849 
secretion  of,  840 
pressure  of,  844 

Uterus,  changes  of,'  during  menstrua- 
tion, 984 
effect  of,  on  mammary  glands,  999 

Utriculus,  function  of,  412 

VAGUS  nerve,   action   of,   on  gastric 

secretion,  780 

on  heart,   585.      See   also  I  in- 
hibition. 

on  pancreas,  794 
as  motor  nerve  to  stomach,  730 
nucleus  of,  249 

relations  of,  to  respiratory  cen- 
ter, 695 

Valin,  799,  1025 
Vasomotor  fibers,  centers  for,  in  cord, 

619 

in  brain,  638 

to  pulmonary  arteries,  627 
nerves,   action  of,  in  heat  regula- 
tion, 968 

course  and  distribution,  610,  620 
general  properties  of  dilators,  621 
history  of  discovery  of,  606 
methods  used  to  demonstrate,  607 
of  heart,  626 

position  of  constrictor  center,  613 
reflex  actions  of,  615 
rhythmical  action  of  constrictor 

center,  619 

to  abdominal  organs,  640 
to  dilator  center  and  reflexes,  622 
to  genital  organs,  640 
to  head,  638 
to  kidneys,  847 
to  skeletal  muscles,  641 
to  trunk  and  limbs,  639 
to  veins,  642 
tonic  activity  of,  613 
Veins,  vasomotor  supply  of,  642 
Velocity  of  blood-flow.     See  Circula- 
tion. 


Velocity  pressure  in  blood-vessels,  514 
Venous  blood-pressures,  509 

cistern,  520 

pulse,  531 

in  brain  sinuses,  635 
Ventilation,  principles  of,  670 
Ventricle.     See  Heart. 
Veratrin,  effect  of,  on  muscle,  31 
Vernix  caseosa,  872 
Vestibular  nerve,  214 
Vestibulospinal  tract  of  spinal  cord, 

181,  235 

Villi,  intestinal,  movements  of,  735 
Vision.    See  Eye  and  Retina. 
Visual  acuity,  343 

center  in  cortex,  207 

field,  binocular,  372 
monocular,  342 

fields,  conflict  of,  in  binocular  vision, 
375 

purple,  338 
Vital  capacity,  657 
Vitamine,  746,  912 
Volume  curve  of  heart,  550 
Voluntary  muscular  contractions,  46 
Vomiting,  741 


WALLERIAN  degeneration,  123,  164 

Warm  spots  of  skin,  281 

Water,    absorption    of,    in    stomach, 

792 

excretion  of,  862 
Weber-Fechner  law,  285 
Wharton's  duct,  758 
Wirsung,  duct  of,  793 
Work  done  by  contracting  muscle,  41 


XANTHIN,  64,  856 

oxidase,  859 
Xanthoproteic  reaction  for  proteins, 

1028 


ZYMOGEN,  755 

granules,  766 
Zymoids,  752 


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